Quick Project Snapshot
Gene-environment interactions in the regulation of cellular plasticity, cognitive function and behaviour
The hippocampus is a dynamic brain structure believed to be critical to cognitive functions including memory consolidation and emotion regulation. One of its unusual features is that the dentate gyrus subfield is known to constitutively engage in the process of neurogenesis throughout adulthood. Interestingly, this process is not static, and behavioural manipulations such as housing animals in an enriched environment (EE), or allowing them to engage in voluntary exercise (VEx) on a running wheel, can increase the rate of hippocampal neurogenesis. The real impact of enhanced hippocampal neuroplasticity on cognitive functions remains unclear and very few studies have used genetically targeted animals to unravel neuroplasticity mechanisms associated with the effects of long-term environmental manipulations.
Serotonin (5-HT) is known to influence adult neurogenesis, with recent studies suggesting that 5-HT in the hippocampus is more instrumental in cell proliferation than in cell survival; this might account for the differences in proliferation and survival observed between VEx and EE. Existing research suggests a sex difference in the regulation of hippocampal neurogenesis as well as sexually dimorphic neurochemical changes underlying the effects of environmental factors on hippocampal-related functions such as memory and emotion regulation.
Clearly, further studies are necessary to substantiate sex differences in gene-environment interactions on hippocampal-related functions. The role of 5-HT in the cellular changes induced by both EE and VEx needs to be explored more exhaustively to elucidate its involvement in the process of neurogenesis. Surprisingly, although they display valuable advantages, no study has yet used genetically targeted animal models with disrupted 5-HT signalling for such fundamental explorations. These questions will be the focus of this project.
Genes Environment and Behaviour Laboratory
Our research includes models of specific neurological and psychiatric disorders which involve cognitive and affective dysfunction, investigated at behavioural, cellular and molecular levels so as to identify pathogenic mechanisms and novel therapeutic targets.
By integrating wide-ranging expertise (including animal behaviour, electrophysiology and molecular/cellular skills) and an extended network, the Genes Environment & Behaviour Laboratory explores how genes and environment combine via experience-dependent plasticity in the healthy and diseased brain.
More specifically, our group has been focusing on projects related to the gene–environment interaction modulating the pathophysiology of Huntington’s disease publishing numerous papers on this topic. As a result, we recently attracted funding from the Brain Foundation and NHMRC.
Supported by my ARC DECRA Fellowship we have started the study of the environmental and pharmacological modulation of behavioural endophenotypes in relevant mouse models of psychiatric disorders (e.g. depression, anxiety, schizophrenia) as well as the investigation of the mechanisms mediating the effects of environmental enrichment and exercise.
Recent publications include:
Mo C, Hannan AJ, Renoir T. Environmental factors as modulators of neurodegeneration: insights from gene-environment interactions in Huntington's disease. Neurosci Biobehav Rev. 2015 May;52:178-92. (PMID: 25770041).
Wright DJ, Renoir T, Smith ZM, Frazier AE, Francis PS, Thorburn DR, McGee SL, Hannan AJ, Gray LJ. N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington's disease. Transl Psychiatry. 2015 Jan 6;5:e492. (PMID: 25562842).
Mo C, Pang TY, Ransome MI, Hill RA, Renoir T, Hannan AJ. High stress hormone levels accelerate the onset of memory deficits in male Huntington's disease mice. Neurobiol Dis. 2014 Sep;69:248-62. (PMID: 24825316).
Renoir T, Hasebe K, Gray L. Mind and body: how the health of the body impacts on neuropsychiatry. Front Pharmacol. 2013 Dec 18;4:158. (PMID: 24385966).
Renoir T. Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: a review of the clinical evidence and the possible mechanisms involved. Front Pharmacol. 2013 Apr 16;4:45. (PMID: 23596418).
Wright DJ, Gray LJ, Finkelstein DI, Crouch PJ, Pow D, Pang T, Li S, Smith ZM, Francis PS, Renoir T, Hannan AJ. N-acetylcysteine modulates glutamatergic dysfunction and depressive behavior in Huntington's disease. Hum Mol Genet. 2016 May 14. (PMID: 27179791)
Rogers J, Vo U, Buret LS, Pang TY, Meiklejohn H, Zeleznikow-Johnston A, Churilov L, van den Buuse M, Hannan AJ, Renoir T. Dissociating the therapeutic effects of environmental enrichment and exercise in a mouse model of anxiety with cognitive impairment. Transl Psychiatry. 2016 Apr 26;6:e794. (PMID: 27115125)
All Projects by this LabGene-environment interactions in the regulation of cellular plasticity, cognitive function and behaviourTherapeutic approaches to dementia and depression in Huntington’s disease
The Division of Behavioural Neuroscience focuses on the use and development of models that reflect aspects of human disorders such as addiction, anxiety, depression, schizophrenia, autism and neurodegenerative conditions such as Huntington’s disease. The Cognitive Neuroscience group additionally studies cognitive disorders caused by diseases such as stroke (cerebrovascular disease), Alzheimer's disease and other dementias from a clinical perspective.