Sandy Stayte is a Research Fellow at the Centre for Neuroscience and Regenerative Medicine in the Faculty of Science. Her work focuses on preclinical investigations of novel therapeutics to halt degeneration and restore motor function in animal models of Parkinson's disease. After being awarded a First Class Honours and the Winifred Dickes Rost Prize at UNSW for her work in Professor Bryce Vissel's lab, Doctor Stayte went on to complete her PhD at UNSW, investigating the role of excitotoxicity and inflammation in Parkinson's disease. During this time Doctor Stayte was awarded a Garvan Young Mentor award for her supervision of junior research students and staff and was selected as a Parkinson's NSW Young Investigator of the Year Finalist in 2015. More recently, her work was ranked in the top 25% of all submitted abstracts for the 2016 World Parkinson's Congress, and she has been successful at obtaining funding from both the Michael J Fox Foundation and Parkinson's NSW.
Scholarships and Awards
- 2016 World Parkinson's Congress Travel Award
- 2016 Parkinson's NSW Young Investigator of the Year Finalist
- 2015 Garvan Award: Young Mentor
- 2014 UNSW Postgraduate Research Student Support Award
- 2010 Australian Postgraduate Award
- 2008 UNSW Winifred Dickes Rost Prize
- 2004 UNSW Sir Arthur and Renee George Scholarship
- 2004 UNSW Harry Manson Travel Scholarship
Can supervise: YES
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: 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.
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: 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.
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: 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.
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: 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.
Stayte, S & Vissel, B 2014, 'Advances in non-dopaminergic pharmacological treatments of Parkinson's disease (vol 8, pg 254, 2014)', FRONTIERS IN NEUROSCIENCE, vol. 8.View/Download from: Publisher's site
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.
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'.
Stayte, SR 2016, 'Activin A is neuroprotective and anti-inflammatory in mouse models of Parkinson's disease'.
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'.
Stayte, SR 2015, 'Neuroprotective action: The potential of growth factors as therapies for Parkinson's disease'.