Can supervise: YES
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: 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.
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: 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: 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: 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.
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'.