Bryce Vissel is a Professor of Neuroscience at UTS and Director of Neuroscience and Regenerative Medicine in the Faculty of Science. His work spans neurodegenerative diseases including Alzheimer’s, Parkinson’s and spinal disorders as well as studies of the neural basis of learning and memory and movement mechanisms.
After being awarded his PhD in medical genetics from the University of Melbourne in 1991, Professor Vissel joined Garvan’s Neuroscience Division, where he was subsequently awarded a National Health and Medical Research Council CJ Martin Fellowship to pursue neuroscience research with Professor Stephen Heinemann at the world-leading Salk Institute in San Diego, USA.
He spent 10 years at Salk, where he authored a number of seminal studies describing molecular mechanisms that regulate synaptic function and their role in behaviour and neurological diseases.
He also received several prestigious awards – a Human Frontiers Award, a Fulbright Award and a Lieberman Award.
In late 2002, Professor Vissel returned to Garvan taking up a position as Head of the Neurodegenerative Diseases group in the Neuroscience Division. His team’s work at the Garvan since then has, among other things, provided new insights into synapse function and shown that the brain has far greater potential for regeneration and repair than previously thought. Professor Vissel is also an important contributor to a number of organisations. He is Chair of the Advisory Board of Cellmid Ltd, a member of the Board of Parkinson’s NSW, and scientific advisor to Alzheimer’s Australia and SpinalCure Australia.
Can supervise: YES
- Neurodegenerative diseases – Alzheimers Disease, Parkinson’s Disease
- Regenerative medicine - spinal cord injury
- Synaptic plasticity
Chia, R, Zhong, H, Vissel, B, Edgerton, VR & Gad, P 2020, 'Novel Activity Detection Algorithm to Characterize Spontaneous Stepping During Multimodal Spinal Neuromodulation After Mid-Thoracic Spinal Cord Injury in Rats', Frontiers in Systems Neuroscience, vol. 13.View/Download from: Publisher's site
© Copyright © 2020 Chia, Zhong, Vissel, Edgerton and Gad. A mid-thoracic spinal cord injury (SCI) severely impairs activation of the lower limb sensorimotor spinal networks, leading to paralysis. Various neuromodulatory techniques including electrical and pharmacological activation of the spinal networks have been successful in restoring locomotor function after SCI. We hypothesized that the combination of self-training in a natural environment with epidural stimulation (ES), quipazine (Quip), and strychnine (Strych) would result in greater activity in a cage environment after paralysis compared to either intervention alone. To assess this, we developed a method measuring and characterizing the chronic EMG recordings from tibialis anterior (TA) and soleus (Sol) muscles while rats were freely moving in their home cages. We then assessed the relationship between the change in recorded activity over time and motor-evoked potentials (MEPs) in animals receiving treatments. We found that the combination of ES, Quip, and Strych (sqES) generated the greatest level of recovery followed by ES + Quip (qES) while ES + Strych (sES) and ES alone showed least improvement in recorded activity. Further, we observed an exponential relationship between late response (LR) component of the MEPs and spontaneously generated step-like activity. Our data demonstrate the feasibility and potential importance of quantitatively monitoring mechanistic factors linked to activity-dependence in response to combinatorial interventions compared to individual therapies after SCI.
Konen, LM, Wright, AL, Royle, GA, Morris, GP, Lau, BK, Seow, PW, Zinn, R, Milham, LT, Vaughan, CW & Vissel, B 2020, 'A new mouse line with reduced GluA2 Q/R site RNA editing exhibits loss of dendritic spines, hippocampal CA1-neuron loss, learning and memory impairments and NMDA receptor-independent seizure vulnerability.', Molecular brain, vol. 13, no. 1, p. 27.View/Download from: Publisher's site
Calcium (Ca2+)-permeable AMPA receptors may, in certain circumstances, contribute to normal synaptic plasticity or to neurodegeneration. AMPA receptors are Ca2+-permeable if they lack the GluA2 subunit or if GluA2 is unedited at a single nucleic acid, known as the Q/R site. In this study, we examined mice engineered with a point mutation in the intronic editing complementary sequence (ECS) of the GluA2 gene, Gria2. Mice heterozygous for the ECS mutation (named GluA2+/ECS(G)) had a ~ 20% reduction in GluA2 RNA editing at the Q/R site. We conducted an initial phenotypic analysis of these mice, finding altered current-voltage relations (confirming expression of Ca2+-permeable AMPA receptors at the synapse). Anatomically, we observed a loss of hippocampal CA1 neurons, altered dendritic morphology and reductions in CA1 pyramidal cell spine density. Behaviourally, GluA2+/ECS(G) mice exhibited reduced motor coordination, and learning and memory impairments. Notably, the mice also exhibited both NMDA receptor-independent long-term potentiation (LTP) and vulnerability to NMDA receptor-independent seizures. These NMDA receptor-independent seizures were rescued by the Ca2+-permeable AMPA receptor antagonist IEM-1460. In summary, unedited GluA2(Q) may have the potential to drive NMDA receptor-independent processes in brain function and disease. Our study provides an initial characterisation of a new mouse model for studying the role of unedited GluA2(Q) in synaptic and dendritic spine plasticity in disorders where unedited GluA2(Q), synapse loss, neurodegeneration, behavioural impairments and/or seizures are observed, such as ischemia, seizures and epilepsy, Huntington's disease, amyotrophic lateral sclerosis, astrocytoma, cocaine seeking behaviour and Alzheimer's disease.
Rentsch, P, Stayte, S, Egan, T, Clark, I & Vissel, B 2020, 'Targeting the cannabinoid receptor CB2 in a mouse model of l-dopa induced dyskinesia.', Neurobiology of Disease, vol. 134, pp. 104646-104646.View/Download from: Publisher's site
L-dopa induced dyskinesia (LID) is a debilitating side-effect of the primary treatment used in Parkinson's disease (PD), l-dopa. Here we investigate the effect of HU-308, a cannabinoid CB2 receptor agonist, on LIDs. Utilizing a mouse model of PD and LIDs, induced by 6-OHDA and subsequent l-dopa treatment, we show that HU-308 reduced LIDs as effectively as amantadine, the current frontline treatment. Furthermore, treatment with HU-308 plus amantadine resulted in a greater anti-dyskinetic effect than maximally achieved with HU-308 alone, potentially suggesting a synergistic effect of these two treatments. Lastly, we demonstrated that treatment with HU-308 and amantadine either alone, or in combination, decreased striatal neuroinflammation, a mechanism which has been suggested to contribute to LIDs. Taken together, our results suggest pharmacological treatments with CB2 agonists merit further investigation as therapies for LIDs in PD patients. Furthermore, since CB2 receptors are thought to be primarily expressed on, and signal through, glia, our data provide weight to suggestion that neuroinflammation, or more specifically, altered glial function, plays a role in development of LIDs.
Stayte, S, Laloli, KJ, Rentsch, P, Lowth, A, Li, KM, Pickford, R & Vissel, B 2020, 'The kainate receptor antagonist UBP310 but not single deletion of GluK1, GluK2, or GluK3 subunits, inhibits MPTP-induced degeneration in the mouse midbrain.', Experimental neurology, vol. 323.View/Download from: UTS OPUS or Publisher's site
The excitatory neurotransmitter glutamate is essential in basal ganglia motor circuits and has long been thought to contribute to cell death and degeneration in Parkinson's disease (PD). While previous research has shown a significant role of NMDA and AMPA receptors in both excitotoxicity and PD, the third class of ionotropic glutamate receptors, kainate receptors, have been less well studied. Given the expression of kainate receptor subunits GluK1-GluK3 in key PD-related brain regions, it has been suggested that GluK1-GluK3 may contribute to excitotoxic cell loss. Therefore the neuroprotective potential of the kainate receptor antagonist UBP310 in animal models of PD was investigated in this study. Stereological quantification revealed administration of UBP310 significantly increased survival of dopaminergic and total neuron populations in the substantia nigra pars compacta in the acute MPTP mouse model of PD. In contrast, UBP310 was unable to rescue MPTP-induced loss of dopamine levels or dopamine transporter expression in the striatum. Furthermore, deletion of GluK1, GluK2 or GluK3 had no effect on MPTP or UBP310-mediated effects across all measures. Interestingly, UBP310 did not attenuate cell loss in the midbrain induced by intrastriatal 6-OHDA toxicity. These results indicate UBP310 provides neuroprotection in the midbrain against MPTP neurotoxicity that is not dependent on specific kainate receptor subunits.
Carter, A, Richards, LJ, Apthorp, D, Azghadi, MR, Badcock, DR, Balleine, B, Bekkers, JM, Berk, M, Bourne, JA, Bradley, AP, Breakspear, M, Brichta, A, Carter, O, Castles, A, Chakli, K, Cohen-Woods, S, Conn, SJ, Cornish, J, Cornish, K, de Zubicaray, G, Egan, GF, Enticott, PG, Fitzgibbon, BM, Forlini, C, Fornito, A, Griffiths, L, Gullifer, J, Hall, W, Halliday, G, Hannan, AJ, Harrer, S, Harvey, A, Hatherly, C, Hickie, IB, Kennett, J, Kiernan, M, Kilpatrick, T, Kiral-Kornek, I, Korgaonkar, MS, Lawrence, AJ, Leventer, R, Levy, N, Licinio, J, Lovell, N, Mackellar, G, Malcolm, L, Mason, A, Mattingley, JB, Medland, SE, Michie, PT, Nithianantharajah, J, Parker, J, Payne, JM, Poole-Warren, L, Sah, P, Sarnyai, Z, Schofield, PR, Shimoni, O, Shum, DHK, Silk, T, Slee, M, Smith, AE, Soulis, T, Sriram, S, Stuart, GJ, Tapson, J, Thompson, MB, van Schaik, A, Vincent, NA, Vissel, B & Waters, A 2020, 'Erratum: A Neuroethics Framework for the Australian Brain Initiative (Neuron (2019) 101(3) (365–369), (S0896627319300054), (10.1016/j.neuron.2019.01.004))', Neuron, vol. 105, no. 1, p. 201.View/Download from: Publisher's site
© 2019 Elsevier Inc. (Neuron 101, 365–369; February 6, 2019) In the original publication of this NeuroView, the member list for the Australian Brain Alliance was omitted. This has now been corrected online. Neuron apologizes for the error.
Clark, IA & Vissel, B 2019, 'Neurodegenerative disease treatments by direct TNF reduction, SB623 cells, maraviroc and irisin and MCC950, from an inflammatory perspective - a Commentary.', Expert review of neurotherapeutics, vol. 19, no. 6, pp. 535-543.View/Download from: UTS OPUS or Publisher's site
Introduction: The importance of excessive cerebral tumor necrosis factor (TNF) concentrations as one of the central tenets of the pathogenesis of the neurodegenerative diseases is now widely known, but variably accepted. Areas covered: Here we update the field by including material that is freely available on the large databases, particularly PubMed. We include the therapeutic outcomes with etanercept (a widely used specific anti-TNF biological), XPro1595 (a new double negative TNF inhibitor), 3,61-dithiothalidomide, implanted SB623 stem cells, maraviroc (a CCR5 inhibitor used to treat AIDS), MCC950 (an NLRP3 inhibitor), and changes in the hormone irisin. Expert opinion: Remarkably, considering the ample literature that links SB623 cells, maraviroc, MCC950 and irisin to TNF, these publications do not mention this cytokine, and therefore not their implicit involvement with controlling its cerebral levels. With regard to developments demonstrated by MCC950, we note that DAMPs and PAMPs recognize and activate both TLRs and inflammasomes in these disease states. Here, as in other illnesses, data suggests that preventing a pathogenic interaction could be achieved through shutting down either of these arms of innate immunity.
Rentsch, P, Stayte, S, Morris, GP & Vissel, B 2019, 'Time dependent degeneration of the nigrostriatal tract in mice with 6-OHDA lesioned medial forebrain bundle and the effect of activin A on L-Dopa induced dyskinesia.', BMC Neuroscience, vol. 20, no. 1.View/Download from: UTS OPUS or Publisher's site
BACKGROUND:Accurately assessing promising therapeutic interventions for human diseases depends, in part, on the reproducibility of preclinical disease models. With the development of transgenic mice, the rapid adaptation of a 6-OHDA mouse model of Parkinson's disease that was originally described for the use in rats has come with a lack of a comprehensive characterization of lesion progression. In this study we therefore first characterised the time course of neurodegeneration in the substantia nigra pars compacta and striatum over a 4 week period following 6-OHDA injection into the medial forebrain bundle of mice. We then utilised the model to assess the anti-dyskinetic efficacy of recombinant activin A, a putative neuroprotectant and anti-inflammatory that is endogenously upregulated during the course of Parkinson's disease. RESULTS:We found that degeneration of fibers in the striatum was fully established within 1 week following 6-OHDA administration, but that the loss of neurons continued to progress over time, becoming fully established 3 weeks after the 6-OHDA injection. In assessing the anti-dyskinetic efficacy of activin A using this model we found that treatment with activin A did not significantly reduce the severity, or delay the time-of-onset, of dyskinesia. CONCLUSION:First, the current study concludes that a 3 week duration is required to establish a complete lesion of the nigrostriatal tract following 6-OHDA injection into the medial forebrain bundle of mice. Second, we found that activin A was not anti-dyskinetic in this model.
Zhong, H, Zhu, C, Minegishi, Y, Richter, F, Zdunowski, S, Roy, RR, Vissel, B, Gad, P, Gerasimenko, Y, Chesselet, M-F & Edgerton, VR 2019, 'Epidural Spinal Cord Stimulation Improves Motor Function in Rats With Chemically Induced Parkinsonism.', Neurorehabilitation and Neural Repair, vol. 33, no. 12, pp. 1029-1039.View/Download from: UTS OPUS or Publisher's site
Background. Epidural stimulation of the spinal cord can reorganize and change the excitability of the neural circuitry to facilitate stepping in rats with a complete spinal cord injury. Parkinson's disease results in abnormal supraspinal signals from the brain to the spinal cord that affect the functional capacity of the spinal networks. Objective. The objective was to determine whether epidural stimulation (electrical enabling motor control, eEmc) of the lumbosacral spinal cord can reorganize the spinal networks to facilitate hindlimb stepping of rats with parkinsonism. Methods. A unilateral 6-OHDA (6-hydroxydopamine) lesion of the nigrostriatal pathway was used to induce parkinsonism. Sham rats (N = 4) were injected in the same region with 0.1% of ascorbic acid. Stimulation electrodes were implanted epidurally at the L2 and S1 (N = 5) or L2 (N = 5) spinal levels. Results. The 6-OHDA rats showed severe parkinsonism in cylinder and adjusting step tests and were unable to initiate stepping when placed in a running wheel and dragged their toes on the affected side during treadmill stepping. During eEmc, the 6-OHDA rats initiated stepping in the running wheel and demonstrated improved stepping quality. Conclusion. Stepping was facilitated in rats with parkinsonism with spinal cord stimulation. The underlying assumption is that the normal functional capacity of spinal networks is affected by supraspinal pathology associated with Parkinson's disease, which either generates insufficient or abnormal descending input to spinal networks and that eEmc can appropriately modulate spinal and supraspinal networks to improve the motor deficits.
Alliance, AB 2019, 'A Neuroethics Framework for the Australian Brain Initiative', Neuron, vol. 101, pp. 365-369.View/Download from: UTS OPUS
Chen, H, Chan, YL, Linnane, C, Mao, Y, Anwer, AG, Sapkota, A, Annissa, TF, Herok, G, Vissel, B, Oliver, BG, Saad, S & Gorrie, CA 2018, 'L-Carnitine and extendin-4 improve outcomes following moderate brain contusion injury.', Scientific reports, vol. 8, no. 1.View/Download from: UTS OPUS or Publisher's site
There is a need for pharmaceutical agents that can reduce neuronal loss and improve functional deficits following traumatic brain injury (TBI). Previous research suggests that oxidative stress and mitochondrial dysfunction play a major role in neuronal damage after TBI. Therefore, this study aimed to investigate two drugs known to have antioxidant effects, L-carnitine and exendin-4, in rats with moderate contusive TBI. L-carnitine (1.5 mM in drinking water) or exendin-4 (15 µg/kg/day, ip) were given immediately after the injury for 2 weeks. Neurological function and brain histology were examined (24 h and 6 weeks post injury). The rats with TBI showed slight sensory, motor and memory functional deficits at 24 h, but recovered by 6 weeks. Both treatments improved sensory and motor functions at 24 h, while only exendin-4 improved memory. Both treatments reduced cortical contusion at 24 h and 6 weeks, however neither affected gliosis and inflammatory cell activation. Oxidative stress was alleviated and mitochondrial reactive oxygen species was reduced by both treatments, however only mitochondrial functional marker protein transporter translocase of outer membrane 20 was increased at 24 h post injury. In conclusion, L-carnitine and exendin-4 treatments immediately after TBI can improve neurological functional outcome and tissue integrity by reducing oxidative stress.
Burchfield, JG, Kebede, MA, Meoli, CC, Stockli, J, Whitworth, PT, Wright, AL, Hoffman, NJ, Minard, AY, Ma, X, Krycer, JR, Nelson, ME, Tan, S-X, Yau, B, Thomas, KC, Wee, NKY, Khor, E-C, Enriquez, RF, Vissel, B, Biden, TJ, Baldock, PA, Hoehn, KL, Cantley, J, Cooney, GJ, James, DE & Fazakerley, DJ 2018, 'High dietary fat and sucrose result in an extensive and time-dependent deterioration in health of multiple physiological systems in mice', JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 293, no. 15, pp. 5731-5745.View/Download from: UTS OPUS or Publisher's site
Clark, IA & Vissel, B 2018, 'The Inflammatory Nature of Post-surgical Delirium Predicts Benefit of Agents With Anti-TNF Effects, Such as Dexmedetomidine.', Frontiers in Neuroscience, vol. 12, pp. 257-257.View/Download from: UTS OPUS or Publisher's site
A characteristic of post-surgery patients, particularly the more elderly, can be a persistent self-propagating cerebral inflammatory syndrome referred to as post-operative cognitive dysfunction (POCD). Changes can be analogous to those seen in Alzheimer's disease (Newman et al., 2007; Steinmetz et al., 2009). Indeed, in some studies the conversion rates to dementia are up to 70% in patients who are 65 years or older (Vanderweyde et al., 2010). An associated transient acute delirium accompanied by increased levels of proinflammatory cytokines, including tumor necrosis factor (TNF), can occur. This sometimes alarming phenomenon can be common in the aged (Inouye et al., 2014), and is often regarded as an extreme manifestation of the sickness behavior caused by cytokines induced during systemic inflammation generated by influences such as trauma or severe infection impinging on a brain vulnerable through already being stressed by these cytokines (Cunningham et al., 2009; Cunningham and Maclullich, 2013; Hennessy et al., 2017).
Recently a report has argued the case that post-surgical delirium can be minimized by prior treatment with dexmedetomidine (Su et al., 2016). Plausible reservations about the form of the trial have been published (Kronzer and Avidan, 2016), and a subsequent trial in which this agent was administered intra-operatively failed to show a response (Deiner et al., 2017). Nevertheless, since a mechanism of action has not yet been suggested, we propose that, should pre-surgical use of dexmedetomidine be confirmed to act against onset of delirium, the capacity of this agent to inhibit excess production of TNF, as demonstrated in various contexts, may well shed light on the field.
Dexmedetomidine (Precedex, Orion Pharma), a synthetic sedative with analgesic and anxiolytic properties, is widely used in surgery. It is a selective α2-adrenoceptor agonist that, compared to opiates, causes little respiratory depression. The reported ability of this agent, a...
Clark, IA & Vissel, B 2018, 'Therapeutic implications of how TNF links apolipoprotein E, phosphorylated tau, alpha-synuclein, amyloid-beta and insulin resistance in neurodegenerative diseases', BRITISH JOURNAL OF PHARMACOLOGY, vol. 175, no. 20, pp. 3859-3875.View/Download from: UTS OPUS or Publisher's site
Mladenova, D, Barry, G, Konen, LM, Pineda, SS, Guennewig, B, Avesson, L, Zinn, R, Schonrock, N, Bitar, M, Jonkhout, N, Crumlish, L, Kaczorowski, DC, Gong, A, Pinese, M, Franco, GR, Walkley, CR, Vissel, B & Mattick, JS 2018, 'Adar3 Is Involved in Learning and Memory in Mice.', Frontiers in Neuroscience, vol. 12.View/Download from: UTS OPUS or Publisher's site
The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals.
Morris, GP, Clark, IA & Vissel, B 2018, 'Questions concerning the role of amyloid-beta in the definition, aetiology and diagnosis of Alzheimer's disease', ACTA NEUROPATHOLOGICA, vol. 136, no. 5, pp. 663-689.View/Download from: Publisher's site
Chan, YL, Saad, S, Machaalani, R, Oliver, BG, Vissel, B, Pollock, C, Jones, NM & Chen, H 2017, 'Maternal Cigarette Smoke Exposure Worsens Neurological Outcomes in Adolescent Offspring with Hypoxic-Ischemic Injury.', Frontiers in Molecular Neuroscience, vol. 10, pp. 1-17.View/Download from: UTS OPUS or Publisher's site
Hypoxic-ischemic (HI) encephalopathy occurs in approximately 6 per 1000 term newborns leading to devastating neurological consequences, such as cerebral palsy and seizures. Maternal smoking is one of the prominent risk factors contributing to HI injury. Mitochondrial integrity plays a critical role in neural injury and repair during HI. We previously showed that maternal cigarette smoke exposure (SE) can reduce brain mitochondrial fission and autophagosome markers in male offspring. This was accompanied by increased brain cell apoptosis (active caspase-3) and DNA fragmentation (TUNEL staining). Here, we aimed to investigate whether maternal SE leads to more severe neurological damage after HI brain injury in male offspring. Female BALB/c mice (8 weeks) were exposed to cigarette smoke prior to mating, during gestation, and lactation. At postnatal day 10, half of the pups from each litter underwent left carotid artery occlusion, followed by exposure to 8% oxygen (92% nitrogen). At postnatal day 40-44, maternal SE reduced grip strength in grip traction and foot fault tests, which were also reduced by HI injury to similar levels regardless of the maternal group. Limb coordination was impaired by maternal SE which was not worsened by HI injury. Maternal SE increased anxiety level in the offspring, which was normalized by HI injury. Apoptosis markers were increased in different brain regions by maternal SE, with the cortex having further increased TUNEL by HI injury, along with increased markers of inflammation and mitophagy. We conclude that maternal SE can worsen HI-induced cellular damage in male offspring well into adolescence.
Clark, IA & Vissel, B 2017, 'The meteorology of cytokine storms, and the clinical usefulness of this knowledge.', Springer Seminars in Immunopathology, vol. 39, no. 5, pp. 505-516.View/Download from: UTS OPUS or Publisher's site
The term cytokine storm has become a popular descriptor of the dramatic harmful consequences of the rapid release of polypeptide mediators, or cytokines, that generate inflammatory responses. This occurs throughout the body in both non-infectious and infectious disease states, including the central nervous system. In infectious disease it has become a useful concept through which to appreciate that most infectious disease is not caused directly by a pathogen, but by an overexuberant innate immune response by the host to its presence. It is less widely known that in addition to these roles in disease pathogenesis these same cytokines are also the basis of innate immunity, and in lower concentrations have many essential physiological roles. Here we update this field, including what can be learned through the history of how these interlinking three aspects of biology and disease came to be appreciated. We argue that understanding cytokine storms in their various degrees of acuteness, severity and persistence is essential in order to grasp the pathophysiology of many diseases, and thus the basis of newer therapeutic approaches to treating them. This particularly applies to the neurodegenerative diseases.
Leake, J, Zinn, R, Corbit, L & Vissel, B 2017, 'Dissociation between complete hippocampal context memory formation and context fear acquisition', LEARNING & MEMORY, vol. 24, no. 4, pp. 153-157.View/Download from: UTS OPUS or Publisher's site
Stayte, S, Rentsch, P, Tröscher, AR, Bamberger, M, Li, KM & Vissel, B 2017, 'Activin A Inhibits MPTP and LPS-Induced Increases in Inflammatory Cell Populations and Loss of Dopamine Neurons in the Mouse Midbrain In Vivo.', PLoS ONE, vol. 12, no. 1, pp. e0167211-e0167211.View/Download from: UTS OPUS or Publisher's site
Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro. We hypothesized that activin A may offer similar anti-inflammatory and neuroprotective effects in in vivo mouse models of Parkinson's disease. We found that activin A significantly attenuated the inflammatory response induced by both MPTP and intranigral administration of lipopolysaccharide in C57BL/6 mice. We found that administration of activin A promoted survival of dopaminergic and total neuron populations in the pars compacta region both 8 days and 8 weeks after MPTP-induced degeneration. Surprisingly, no corresponding protection of striatal dopamine levels was found. Furthermore, activin A failed to protect against loss of striatal dopamine transporter expression in the striatum, suggesting the neuroprotective action of activin A may be localized to the substantia nigra. Together, these results provide the first evidence that activin A exerts potent neuroprotection and anti-inflammatory effects in the MPTP and lipopolysaccharide mouse models of Parkinson's disease.
Clark, IA & Vissel, B 2016, 'Excess cerebral TNF causing glutamate excitotoxicity rationalizes treatment of neurodegenerative diseases and neurogenic pain by anti-TNF agents.', Journal of Neuroinflammation, vol. 13, no. 1, pp. 1-16.View/Download from: UTS OPUS or Publisher's site
The basic mechanism of the major neurodegenerative diseases, including neurogenic pain, needs to be agreed upon before rational treatments can be determined, but this knowledge is still in a state of flux. Most have agreed for decades that these disease states, both infectious and non-infectious, share arguments incriminating excitotoxicity induced by excessive extracellular cerebral glutamate. Excess cerebral levels of tumor necrosis factor (TNF) are also documented in the same group of disease states. However, no agreement exists on overarching mechanism for the harmful effects of excess TNF, nor, indeed how extracellular cerebral glutamate reaches toxic levels in these conditions. Here, we link the two, collecting and arguing the evidence that, across the range of neurodegenerative diseases, excessive TNF harms the central nervous system largely through causing extracellular glutamate to accumulate to levels high enough to inhibit synaptic activity or kill neurons and therefore their associated synapses as well. TNF can be predicted from the broader literature to cause this glutamate accumulation not only by increasing glutamate production by enhancing glutaminase, but in addition simultaneously reducing glutamate clearance by inhibiting re-uptake proteins. We also discuss the effects of a TNF receptor biological fusion protein (etanercept) and the indirect anti-TNF agents dithio-thalidomides, nilotinab, and cannabinoids on these neurological conditions. The therapeutic effects of 6-diazo-5-oxo-norleucine, ceptriaxone, and riluzole, agents unrelated to TNF but which either inhibit glutaminase or enhance re-uptake proteins, but do not do both, as would anti-TNF agents, are also discussed in this context. By pointing to excess extracellular glutamate as the target, these arguments greatly strengthen the case, put now for many years, to test appropriately delivered ant-TNF agents to treat neurodegenerative diseases in randomly controlled trials.
Michie, PT, Badcock, DR, Bartlett, PF, Bekkers, JM, Bourne, JA, Castles, A, Egan, GF, Fornito, A, Hannan, AJ, Hickie, IB, Mattingley, JB, Richards, LJ, Schofield, PR, Shum, DHK, Stu-Art, GJ, Vickers, JC & Vissel, B 2016, 'Australian Brain Alliance', NEURON, vol. 92, no. 3, pp. 597-600.View/Download from: Publisher's site
Morris, GP, Wright, AL, Tan, RP, Gladbach, A, Ittner, LM & Vissel, B 2016, 'A Comparative Study of Variables Influencing Ischemic Injury in the Longa and Koizumi Methods of Intraluminal Filament Middle Cerebral Artery Occlusion in Mice.', PLoS ONE, vol. 11, no. 2, pp. 1-34.View/Download from: UTS OPUS or Publisher's site
The intraluminal filament model of middle cerebral artery occlusion (MCAO) in mice and rats has been plagued by inconsistency, owing in part to the multitude of variables requiring control. In this study we investigated the impact of several major variables on survival rate, lesion volume, neurological scores, cerebral blood flow (CBF) and body weight including filament width, time after reperfusion, occlusion time and the choice of surgical method. Using the Koizumi method, we found ischemic injury can be detected as early as 30 min after reperfusion, to a degree that is not statistically different from 24 h post-perfusion, using 2,3,5-Triphenyltetrazolium chloride (TTC) staining. We also found a distinct increase in total lesion volume with increasing occlusion time, with 30-45 min a critical time for the development of large, reproducible lesions. Furthermore, although we found no significant difference in total lesion volume generated by the Koizumi and Longa methods of MCAO, nor were survival rates appreciably different between the two at 4 h after reperfusion, the Longa method produces significantly greater reperfusion. Finally, we found no statistical evidence to support the exclusion of data from animals experiencing a CBF reduction of <70% in the MCA territory following MCAO, using laser-Doppler flowmetry. Instead we suggest the main usefulness of laser-Doppler flowmetry is for guiding filament placement and the identification of subarachnoid haemorrhages and premature reperfusion. In summary, this study provides detailed evaluation of the Koizumi method of intraluminal filament MCAO in mice and a direct comparison to the Longa method.
Clark, IA & Vissel, B 2015, 'A Neurologist's Guide to TNF Biology and to the Principles behind the Therapeutic Removal of Excess TNF in Disease', NEURAL PLASTICITY.View/Download from: UTS OPUS or Publisher's site
Clark, IA & Vissel, B 2015, 'Amyloid : one of three danger-associated molecules that are secondary inducers of the proinflammatory cytokines that mediate Alzheimer's disease', BRITISH JOURNAL OF PHARMACOLOGY, vol. 172, no. 15, pp. 3714-3727.View/Download from: UTS OPUS or Publisher's site
Stayte, S, Rentsch, P, Li, KM & Vissel, B 2015, 'Activin A protects midbrain neurons in the 6-hydroxydopamine mouse model of Parkinson's disease.', PLoS ONE, vol. 10, no. 4, pp. 1-15.View/Download from: UTS OPUS or Publisher's site
Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta (SNpc) and a subsequent loss of dopamine (DA) within the striatum. Despite advances in the development of pharmacological therapies that are effective at alleviating the symptoms of PD, the search for therapeutic treatments that halt or slow the underlying nigral degeneration remains a particular challenge. Activin A, a member of the transforming growth factor β superfamily, has been shown to play a role in the neuroprotection of midbrain neurons against 6-hydroxydopamine (6-OHDA) in vitro, suggesting that activin A may offer similar neuroprotective effects in in vivo models of PD. Using robust stereological methods, we found that intrastriatal injections of 6-OHDA results in a significant loss of both TH positive and NeuN positive populations in the SNpc at 1, 2, and 3 weeks post-lesioning in drug naïve mice. Exogenous application of activin A for 7 days, beginning the day prior to 6-OHDA administration, resulted in a significant survival of both dopaminergic and total neuron numbers in the SNpc against 6-OHDA-induced toxicity. However, we found no corresponding protection of striatal DA or dopamine transporter (DAT) expression levels in animals receiving activin A compared to vehicle controls. These results provide the first evidence that activin A exerts potent neuroprotection in a mouse model of PD, however this neuroprotection may be localized to the midbrain.
The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities.
Morris, GP, Clark, IA & Vissel, B 2014, 'Inconsistencies and controversies surrounding the amyloid hypothesis of Alzheimer's disease.', Acta Neuropathologica Communications, vol. 2, pp. 1-21.View/Download from: UTS OPUS or Publisher's site
The amyloid hypothesis has driven drug development strategies for Alzheimer's disease for over 20 years. We review why accumulation of amyloid-beta (Aβ) oligomers is generally considered causal for synaptic loss and neurodegeneration in AD. We elaborate on and update arguments for and against the amyloid hypothesis with new data and interpretations, and consider why the amyloid hypothesis may be failing therapeutically. We note several unresolved issues in the field including the presence of Aβ deposition in cognitively normal individuals, the weak correlation between plaque load and cognition, questions regarding the biochemical nature, presence and role of Aβ oligomeric assemblies in vivo, the bias of pre-clinical AD models toward the amyloid hypothesis and the poorly explained pathological heterogeneity and comorbidities associated with AD. We also illustrate how extensive data cited in support of the amyloid hypothesis, including genetic links to disease, can be interpreted independently of a role for Aβ in AD. We conclude it is essential to expand our view of pathogenesis beyond Aβ and tau pathology and suggest several future directions for AD research, which we argue will be critical to understanding AD pathogenesis.
Since the 1960's treatments for Parkinson's disease (PD) have traditionally been directed to restore or replace dopamine, with L-Dopa being the gold standard. However, chronic L-Dopa use is associated with debilitating dyskinesias, limiting its effectiveness. This has resulted in extensive efforts to develop new therapies that work in ways other than restoring or replacing dopamine. Here we describe newly emerging non-dopaminergic therapeutic strategies for PD, including drugs targeting adenosine, glutamate, adrenergic, and serotonin receptors, as well as GLP-1 agonists, calcium channel blockers, iron chelators, anti-inflammatories, neurotrophic factors, and gene therapies. We provide a detailed account of their success in animal models and their translation to human clinical trials. We then consider how advances in understanding the mechanisms of PD, genetics, the possibility that PD may consist of multiple disease states, understanding of the etiology of PD in non-dopaminergic regions as well as advances in clinical trial design will be essential for ongoing advances. We conclude that despite the challenges ahead, patients have much cause for optimism that novel therapeutics that offer better disease management and/or which slow disease progression are inevitable.
Clark, IA & Vissel, B 2013, 'Treatment implications of the altered cytokine-insulin axis in neurodegenerative disease', BIOCHEMICAL PHARMACOLOGY, vol. 86, no. 7, pp. 862-871.View/Download from: UTS OPUS or Publisher's site
Morris, GP, Clark, IA, Zinn, R & Vissel, B 2013, 'Microglia: A new frontier for synaptic plasticity, learning and memory, and neurodegenerative disease research', NEUROBIOLOGY OF LEARNING AND MEMORY, vol. 105, pp. 40-53.View/Download from: UTS OPUS or Publisher's site
Wright, AL, Zinn, R, Hohensinn, B, Konen, LM, Beynon, SB, Tan, RP, Clark, IA, Abdipranoto, A & Vissel, B 2013, 'Neuroinflammation and neuronal loss precede Aβ plaque deposition in the hAPP-J20 mouse model of Alzheimer's disease.', PLoS ONE, vol. 8, no. 4, pp. 1-14.View/Download from: UTS OPUS or Publisher's site
Recent human trials of treatments for Alzheimer's disease (AD) have been largely unsuccessful, raising the idea that treatment may need to be started earlier in the disease, well before cognitive symptoms appear. An early marker of AD pathology is therefore needed and it is debated as to whether amyloid-βAβ? plaque load may serve this purpose. We investigated this in the hAPP-J20 AD mouse model by studying disease pathology at 6, 12, 24 and 36 weeks. Using robust stereological methods, we found there is no neuron loss in the hippocampal CA3 region at any age. However loss of neurons from the hippocampal CA1 region begins as early as 12 weeks of age. The extent of neuron loss increases with age, correlating with the number of activated microglia. Gliosis was also present, but plateaued during aging. Increased hyperactivity and spatial memory deficits occurred at 16 and 24 weeks. Meanwhile, the appearance of plaques and oligomeric Aβ were essentially the last pathological changes, with significant changes only observed at 36 weeks of age. This is surprising given that the hAPP-J20 AD mouse model is engineered to over-expresses Aβ. Our data raises the possibility that plaque load may not be the best marker for early AD and suggests that activated microglia could be a valuable marker to track disease progression.
Zelikowsky, M, Bissiere, S, Hast, TA, Bennett, RZ, Abdipranoto, A, Vissel, B & Fanselow, MS 2013, 'Prefrontal microcircuit underlies contextual learning after hippocampal loss', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 110, no. 24, pp. 9938-9943.View/Download from: UTS OPUS or Publisher's site
Clark, I, Atwood, C, Bowen, R, Paz-Filho, G & Vissel, B 2012, 'Tumor Necrosis Factor-Induced Cerebral Insulin Resistance in Alzheimer's Disease Links Numerous Treatment Rationales', PHARMACOLOGICAL REVIEWS, vol. 64, no. 4, pp. 1004-1026.View/Download from: UTS OPUS or Publisher's site
Wright, A & Vissel, B 2012, 'The essential role of AMPA receptor GluA2 subunit RNA editing in the normal and diseased brain', FRONTIERS IN MOLECULAR NEUROSCIENCE, vol. 5.View/Download from: UTS OPUS or Publisher's site
Clark, IA, Alleva, LM & Vissel, B 2011, 'TNF and Leptin Tell Essentially the Same Story in Alzheimer's Disease', JOURNAL OF ALZHEIMERS DISEASE, vol. 26, no. 2, pp. 201-205.View/Download from: UTS OPUS or Publisher's site
McRoberts, JA, Ennes, HS, Marvizon, JCG, Fanselow, MS, Mayer, EA & Vissel, B 2011, 'SELECTIVE KNOCKDOWN OF NMDA RECEPTORS IN PRIMARY AFFERENT NEURONS DECREASES PAIN DURING PHASE 2 OF THE FORMALIN TEST', NEUROSCIENCE, vol. 172, pp. 474-482.View/Download from: UTS OPUS or Publisher's site
Wiltgen, BJ, Royle, GA, Gray, EE, Abdipranoto, A, Thangthaeng, N, Jacobs, N, Saab, F, Tonegawa, S, Heinemann, SF, O'Dell, TJ, Fanselow, MS & Vissel, B 2010, 'A Role for Calcium-Permeable AMPA Receptors in Synaptic Plasticity and Learning', PLOS ONE, vol. 5, no. 9.View/Download from: UTS OPUS or Publisher's site
Abdipranoto-Cowley, A, Park, JS, Croucher, D, Daniel, J, Henshall, S, Galbraith, S, Mervin, K & Vissel, B 2009, 'Activin A Is Essential for Neurogenesis Following Neurodegeneration', STEM CELLS, vol. 27, no. 6, pp. 1330-1346.View/Download from: Publisher's site
Daniel, JA, Galbraith, S, Iacovitti, L, Abdipranoto, A & Vissel, B 2009, 'Functional Heterogeneity at Dopamine Release Sites', JOURNAL OF NEUROSCIENCE, vol. 29, no. 46, pp. 14670-14680.View/Download from: Publisher's site
Goetz, J, Schonrock, N, Vissel, B & Ittner, LM 2009, 'Alzheimer's Disease Selective Vulnerability and Modeling in Transgenic Mice', JOURNAL OF ALZHEIMERS DISEASE, vol. 18, no. 2, pp. 243-251.View/Download from: UTS OPUS or Publisher's site
Abdipranoto, A, Wu, S, Stayte, S & Vissel, B 2008, 'The Role of Neurogenesis in Neurodegenerative Diseases and its Implications for Therapeutic Development', CNS & NEUROLOGICAL DISORDERS-DRUG TARGETS, vol. 7, no. 2, pp. 187-210.View/Download from: Publisher's site
Youn, D-H, Royle, G, Kolaj, M, Vissel, B & Randic, M 2008, 'Enhanced LTP of primary afferent neurotransmission in AMPA receptor GluR2-deficient mice', PAIN, vol. 136, no. 1-2, pp. 158-167.View/Download from: Publisher's site
Gray, EE, Fink, AE, Sarinana, J, Vissel, B & O'Dell, TJ 2007, 'Long-term potentiation in the hippocampal CA1 region does not require insertion and activation of GluR2-lacking AMPA receptors', JOURNAL OF NEUROPHYSIOLOGY, vol. 98, no. 4, pp. 2488-2492.View/Download from: Publisher's site
Hinshelwood, RA, Huschtscha, LI, Melki, J, Stirzaker, C, Abdipranoto, A, Vissel, B, Ravasi, T, Wells, CA, Hume, DA, Reddel, RR & Clark, SJ 2007, 'Concordant epigenetic silencing of transforming growth factor-beta signaling pathway genes occurs early in breast carcinogenesis', CANCER RESEARCH, vol. 67, no. 24, pp. 11517-11527.View/Download from: Publisher's site
Thomas, CG, Krupp, JJ, Bagley, EE, Bauzon, R, Heinemann, SF, Vissel, B & Westbrook, GL 2006, 'Probing N-methyl-D-aspartate receptor desensitization with the substituted-cysteine accessibility method', MOLECULAR PHARMACOLOGY, vol. 69, no. 4, pp. 1296-1303.View/Download from: Publisher's site
Hauser, KF, Aldrich, JV, Anderson, KJ, Bakalkin, G, Christie, MJ, Hall, ED, Knapp, PE, Scheff, SW, Singh, IN, Vissel, B, Woods, AS, Yakovleva, T & Shippenberg, TS 2005, 'Pathobiology of dynorphins in trauma and disease', FRONTIERS IN BIOSCIENCE-LANDMARK, vol. 10, pp. 216-235.View/Download from: Publisher's site
Sonner, JM, Vissel, B, Royle, G, Maurer, A, Gong, D, Baron, NV, Harrison, N, Fanselow, M & Eger, EI 2005, 'The effect of three inhaled anesthetics in mice harboring mutations in the GluR6 (Kainate) receptor gene', ANESTHESIA AND ANALGESIA, vol. 101, no. 1, pp. 143-148.View/Download from: Publisher's site
Petralia, RS, Sans, N, Wang, YX, Vissel, B, Chang, K, Noben-Trauth, K, Heinemann, SF & Wenthold, RJ 2004, 'Loss of GLUR2 alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor subunit differentially affects remaining synaptic glutamate receptors in cerebellum and cochlear nuclei', EUROPEAN JOURNAL OF NEUROSCIENCE, vol. 19, no. 8, pp. 2017-2029.View/Download from: Publisher's site
Petralia, RS, Sans, N, Wang, YX, Vissel, B, Chang, K, Noben-Trauth, K, Heinemann, SF & Wenthold, RJ 2004, 'Loss of GLUR2 α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptor subunit differentially affects remaining synaptic glutamate receptors in cerebellum and cochlear nuclei', European Journal of Neuroscience, vol. 19, no. 8, pp. 2017-2029.View/Download from: Publisher's site
The α-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA) type of ionotropic glutamate receptor is the major mediator of fast neurotransmission in the brain and spinal cord. Most AMPA receptors are impermeable to calcium because they contain the GluR2 subunit. However, some AMPA receptors lack GluR2 and pass calcium which can mediate synaptic plasticity and, in excess, neurotoxicity. Previously, we showed a decrease in the density of synaptic AMPA receptors in the hippocampus of mice lacking GluR2. In this study, using these GluR2-lacking mice, we examined other areas of the brain that differ in the amount of GluR2 normally present. Like hippocampal spines, cerebellar Purkinje spines normally express AMPA receptors with high GluR2 and showed a decrease in synaptic AMPA receptors in mutant mice. In contrast, neurons that normally express AMPA receptors with little or no GluR2, such as in the anteroventral cochlear nucleus, showed no decrease in AMPA receptors and even showed an increase in one AMPA receptor subunit. These two different patterns may relate to preadaptations to prevent calcium neurotoxicity; such mechanisms might be absent in Purkinje and hippocampal spines so that these neurons must decrease their total expression of synaptic AMPA receptors (calcium permeable in mutant mice) to prevent calcium neurotoxicity. In addition, we found that another glutamate receptor, GluRδ2, which is abundant only in parallel fibre synapses on Purkinje cells and in the dorsal cochlear nucleus, is up-regulated at these synapses in mutant mice; this probably reflects some change in GluRδ2 targeting to these synapses.
Sonner, JM, Antognini, JF, Dutton, RC, Flood, P, Gray, AT, Harris, RA, Homanics, GE, Kendig, J, Orser, B, Raines, DE, Rampil, IJ, Trudell, J, Vissel, B & Eger, EI 2004, 'Erratum: Inhaled Anesthetics and Immobility: Mechanisms, Mysteries, and Minimum Alveolar Anesthetic Concentration (Anesthesia and Analgesia (September 2003) 97 (718-740))', Anesthesia and Analgesia, vol. 98, no. 1, p. 29.
Sans, N, Vissel, B, Petralia, RS, Wang, YX, Chang, K, Royle, GA, Wang, CY, O'Gorman, S, Heinemann, SF & Wenthold, RJ 2003, 'Aberrant formation of glutamate receptor complexes in hippocampal neurons of mice lacking the GluR2 AMPA receptor subunit', JOURNAL OF NEUROSCIENCE, vol. 23, no. 28, pp. 9367-9373.
Sekirnjak, C, Vissel, B, Bollinger, J, Faulstich, M & du Lac, S 2003, 'Purkinje cell Synapses target physiologically unique brainstem neurons', JOURNAL OF NEUROSCIENCE, vol. 23, no. 15, pp. 6392-6398.
Sonner, JM, Antognini, JF, Dutton, RC, Flood, P, Gray, AT, Harris, RA, Homanics, GE, Kendig, J, Orser, B, Raines, DE, Trudell, J, Vissel, B & Eger, EI 2003, 'Inhaled anesthetics and immobility: Mechanisms, mysteries, and minimum alveolar anesthetic concentration', ANESTHESIA AND ANALGESIA, vol. 97, no. 3, pp. 718-740.View/Download from: Publisher's site
South, SM, Kohno, T, Kaspar, BK, Hegarty, D, Vissel, B, Drake, CT, Ohata, M, Jenab, S, Sailer, AW, Malkmus, S, Masuyama, T, Horner, P, Bogulavsky, J, Gage, FH, Yaksh, TL, Woolf, CJ, Heinemann, SF & Inturrisi, CE 2003, 'A conditional deletion of the NR1 subunit of the NMDA receptor in adult spinal cord dorsal horn reduces NMDA currents and injury-induced pain', JOURNAL OF NEUROSCIENCE, vol. 23, no. 12, pp. 5031-5040.
Kaspar, BK, Vissel, B, Bengoechea, T, Crone, S, Randolph-Moore, L, Muller, R, Brandon, EP, Schaffer, D, Verma, IM, Lee, KF, Heinemann, SF & Gage, FH 2002, 'Adeno-associated virus effectively mediates conditional gene modification in the brain', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 99, no. 4, pp. 2320-2325.View/Download from: Publisher's site
Krupp, JJ, Vissel, B, Thomas, CG, Heinemann, SF & Westbrook, GL 2002, 'Calcineurin acts via the C-terminus of NR2A to modulate desensitization of NMDA receptors', NEUROPHARMACOLOGY, vol. 42, no. 5, pp. 593-602.View/Download from: Publisher's site
Luo, JH, Fu, ZY, Losi, G, Kim, BG, Prybylowski, K, Vissel, B & Vicini, S 2002, 'Functional expression of distinct NMDA channel subunits tagged with green fluorescent protein in hippocampal neurons in culture', NEUROPHARMACOLOGY, vol. 42, no. 3, pp. 306-318.View/Download from: Publisher's site
Vissel, B, Krupp, JJ, Heinemann, SF & Westbrook, GL 2002, 'Intracellular domains of NR2 alter calcium-dependent inactivation of N-methyl-D-aspartate receptors', MOLECULAR PHARMACOLOGY, vol. 61, no. 3, pp. 595-605.View/Download from: Publisher's site
Vissel, B, Krupp, JJ, Heinemann, SE & Westbrook, GL 2001, 'A use-dependent tyrosine dephosphorylation of NMDA receptors is independent of ion flux', NATURE NEUROSCIENCE, vol. 4, no. 6, pp. 587-596.View/Download from: Publisher's site
Vissel, B, Royle, GA, Christie, BR, Schiffer, HH, Ghetti, A, Tritto, T, Perez-Otano, I, Radcliffe, RA, Seamans, J, Sejnowski, T, Wehner, JM, Collins, AC, O'Gorman, S & Heinemann, SF 2001, 'The role of RNA editing of kainate receptors in synaptic plasticity and seizures', NEURON, vol. 29, no. 1, pp. 217-227.View/Download from: Publisher's site
Krupp, JJ, Vissel, B, Thomas, CG, Heinemann, SF & Westbrook, GL 1999, 'Interactions of calmodulin and alpha-actinin with the NR1 subunit modulate Ca2+-dependent inactivation of NMDA receptors', JOURNAL OF NEUROSCIENCE, vol. 19, no. 4, pp. 1165-1178.
Krupp, JJ, Vissel, B, Heinemann, SF & Westbrook, GL 1998, 'N-terminal domains in the NR2 subunit control desensitization of NMDA receptors', NEURON, vol. 20, no. 2, pp. 317-327.View/Download from: Publisher's site
Westbrook, GL, Krupp, JJ & Vissel, B 1997, 'Cytoskeletal interactions with glutamate receptors at central synapses', CYTOSKELETAL REGULATION OF MEMBRANE FUNCTION, vol. 52, pp. 163-175.
Westbrook, GL, Krupp, JJ & Vissel, B 1997, 'Cytoskeletal interactions with glutamate receptors at central synapses.', Society of General Physiologists series, vol. 52, pp. 163-175.
The data presented here are clearly just the beginning of any comprehensive understanding of the set of regulatory and cytoskeletal proteins that interact with membrane receptors in the postsynaptic density. They do, however, indicate that both glutamate channels at central excitatory synapses are involved in complex protein-protein interactions. For example, while NR2A is important for Ca-dependent inactivation of NMDA receptors, studies in several systems suggest that the other major NR2 subunit in hippocampal neurons, NR2B, predominates at critical times during synapse formation. In addition, the COOH terminus of NR2B binds to several novel cytoskeletal proteins. These results provide circumstantial evidence that NR2B may play specific roles in function and localization of receptors at excitatory synapses. The possible role of NR2B in early synaptic function gains additional support from functional data suggesting that NMDA receptors have specific roles during development (Komuro and Rakic, 1993; Rabacchi et al., 1992; Yen et al., 1993). The essential role of NR1 and NR2B in development is graphically demonstrated by the neonatal death of transgenic mice lacking either of these two subunits (Forrest et al., 1994; Kutsuwada et al., 1996) whereas NR2A and NR2C-deficient mice are less severely affected (Sakimura et al., 1995; Ebralidze et al., 1996).
Krupp, JJ, Vissel, B, Heinemann, SF & Westbrook, GL 1996, 'Calcium-dependent inactivation of recombinant N-methyl-D-aspartate receptors is NR2 subunit specific', MOLECULAR PHARMACOLOGY, vol. 50, no. 6, pp. 1680-1688.
KALITSIS, P, EARLE, E, VISSEL, B, SHAFFER, LG & CHOO, KHA 1993, 'A CHROMOSOME-13-SPECIFIC HUMAN SATELLITE-I DNA SUBFAMILY WITH MINOR PRESENCE ON CHROMOSOME-21 - FURTHER-STUDIES ON ROBERTSONIAN TRANSLOCATIONS', GENOMICS, vol. 16, no. 1, pp. 104-112.View/Download from: Publisher's site
TROWELL, HE, NAGY, A, VISSEL, B & CHOO, KHA 1993, 'LONG-RANGE ANALYSES OF THE CENTROMERIC REGIONS OF HUMAN CHROMOSOME-13, CHROMOSOME-14 AND CHROMOSOME-21 - IDENTIFICATION OF A NARROW DOMAIN-CONTAINING 2 KEY CENTROMERIC DNA ELEMENTS', HUMAN MOLECULAR GENETICS, vol. 2, no. 10, pp. 1639-1649.View/Download from: Publisher's site
CHOO, KHA, EARLE, E, VISSEL, B & KALITSIS, P 1992, 'A CHROMOSOME-14-SPECIFIC HUMAN SATELLITE-III DNA SUBFAMILY THAT SHOWS VARIABLE PRESENCE ON DIFFERENT CHROMOSOMES-14', AMERICAN JOURNAL OF HUMAN GENETICS, vol. 50, no. 4, pp. 706-716.
VISSEL, B & CHOO, KHA 1992, 'EVOLUTIONARY RELATIONSHIPS OF MULTIPLE ALPHA SATELLITE SUBFAMILIES IN THE CENTROMERES OF HUMAN-CHROMOSOMES 13, 14, AND 21', JOURNAL OF MOLECULAR EVOLUTION, vol. 35, no. 2, pp. 137-146.
VISSEL, B, NAGY, A & CHOO, KHA 1992, 'A SATELLITE-III SEQUENCE SHARED BY HUMAN CHROMOSOME-13, CHROMOSOME-14, AND CHROMOSOME-21 THAT IS CONTIGUOUS WITH ALPHA-SATELLITE DNA', CYTOGENETICS AND CELL GENETICS, vol. 61, no. 2, pp. 81-86.View/Download from: Publisher's site
CHOO, KH 1991, 'CORRECTION', NUCLEIC ACIDS RESEARCH, vol. 19, no. 8, pp. 1979-1979.View/Download from: Publisher's site
CHOO, KH, VISSEL, B, NAGY, A, EARLE, E & KALITSIS, P 1991, 'A SURVEY OF THE GENOMIC DISTRIBUTION OF ALPHA-SATELLITE DNA ON ALL THE HUMAN-CHROMOSOMES, AND DERIVATION OF A NEW CONSENSUS SEQUENCE', NUCLEIC ACIDS RESEARCH, vol. 19, no. 6, pp. 1179-1182.View/Download from: Publisher's site
VISSEL, B & CHOO, KH 1991, '4 DISTINCT ALPHA-SATELLITE SUBFAMILIES SHARED BY HUMAN CHROMOSOME-13, CHROMOSOME-14 AND CHROMOSOME-21', NUCLEIC ACIDS RESEARCH, vol. 19, no. 2, pp. 271-277.View/Download from: Publisher's site
CHOO, KH, EARLE, E, VISSEL, B & FILBY, RG 1990, 'IDENTIFICATION OF 2 DISTINCT SUBFAMILIES OF ALPHA-SATELLITE DNA THAT ARE HIGHLY SPECIFIC FOR HUMAN CHROMOSOME-15', GENOMICS, vol. 7, no. 2, pp. 143-151.View/Download from: Publisher's site
VISSEL, B & CHOO, KH 1989, 'MOUSE MAJOR (GAMMA) SATELLITE DNA IS HIGHLY CONSERVED AND ORGANIZED INTO EXTREMELY LONG TANDEM ARRAYS - IMPLICATIONS FOR RECOMBINATION BETWEEN NONHOMOLOGOUS CHROMOSOMES', GENOMICS, vol. 5, no. 3, pp. 407-414.View/Download from: Publisher's site
CHOO, KH, VISSEL, B, BROWN, R, FILBY, RG & EARLE, E 1988, 'HOMOLOGOUS ALPHA-SATELLITE SEQUENCES ON HUMAN ACROCENTRIC CHROMOSOMES WITH SELECTIVITY FOR CHROMOSOMES 13, 14 AND 21 - IMPLICATIONS FOR RECOMBINATION BETWEEN NONHOMOLOGUES AND ROBERTSONIAN TRANSLOCATIONS', NUCLEIC ACIDS RESEARCH, vol. 16, no. 4, pp. 1273-1283.View/Download from: Publisher's site
VISSEL, B & CHOO, KH 1988, 'ALTERED ACTIVITY OF RESTRICTION ENDONUCLEASE MN1-I CLEAVAGE OF MOUSE SATELLITE DNA', NUCLEIC ACIDS RESEARCH, vol. 16, no. 10, pp. 4731-4731.View/Download from: Publisher's site
Götz, J, Schonrock, N, Vissel, B & Ittner, LM 2011, 'Alzheimer's disease selective vulnerability and modelling in transgenic mice' in Casadesus, G (ed), Volume 1: Handbook of Animal Models in Alzheimer's Disease, IOS Press, The Netherlands, pp. 49-58.View/Download from: UTS OPUS or Publisher's site
Neurodegenerative diseases are characterized by 'hot spots' of degeneration. The regions of primary vulnerability vary between different neurodegenerative diseases. Within these regions, some neurons are lost whereas others that are morphologically indiscriminable survive. The enigma of this selective vulnerability is tightly linked to two fundamental problems in the neurosciences. Firstly, it is not understood how many neuronal cell types make up the mammalian brain; estimates are in the order of more than thousand. Secondly, the mechanisms by which some nerve cells undergo functional impairment followed by degeneration while others do not, remain elusive. Understanding the basis for this selective vulnerability has significant implications for understanding the pathogenesis of disease and for developing treatments. Here, we review what is known about selective vulnerability in Alzheimer's disease, frontotemporal dementia and Parkinson's disease. We suggest, since transgenic animal models of disease reproduce aspects of selective vulnerability, that these models offer a valuable system for future investigations into the physiological basis of selective vulnerability. © 2011 The authors and IOS Press. All rights reserved.
Morris, GP, Wright, AL, Stayte, S, Zinn, R, Tan, RP & Vissel, B 2017, 'Attaining reliable data in pre-clinical mouse models of middle cerebral artery occlusion: a case study with brain-derived and glial-derived neurotrophic factors'.
Morris, GP, Wright, AL, Stayte, S, Zinn, R, Tan, RP & Vissel, B 2016, 'The neuroprotective capabilities of glial-derived neurotrophic factor following intraluminal filament middle cerebral artery occlusion in mice'.