Quick Project Snapshot
Investigation of paternal influence on offspring mental health
As diploid animals, each individual human being is a genetic combination of their parents. Emerging evidence now indicates that the environment that our parents were exposed to can also influence us. The potential for maternal health and well-being to impact on the development of their offspring is well demonstrated and established. Stress during pregnancy has a negative impact on offspring by slowing developmental milestones, cognitive growth, and is also associated with adult-onset mental disorders. In contrast, the paternal influence on offspring development and mental health is largely unknown. Given the increasing exposure to stressors (physical , psychosocial and occupational) that are prevalent in our society, it is important to investigate the possible transgenerational effects of stress on the mental health of future generations. Our lab has developed a model of elevated physiological stress in mice. Male mice are administered the stress hormone corticosterone via their drinking water, resulting in behavioural alterations associated with anxiety and depression. We have subsequently found that the offspring of these mice also exhibit alterations in anxiety and depressive tests. Interestingly, the effects on male offspring seem to be detrimental compared to female offspring that appear to be more resilient.
Our lab is keen to expand on those findings by investigating potential environmental modifiers of these behaviours. We have adopted several hypotheses which we are offering as potential projects. The first is a study of exercise and how the cognitive ability and response to stress of offspring born to exercising fathers might be changed. The second study will explore enhanced cognitive stimulation as a protectant for offspring born to stressed fathers. A third study would explore the benefits of regular exercise in preventing the transgenerational effects of stress in fathers.
- 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;69:248-62.
- Pang TY, Du X, Catchlove WA, Renoir T, Lawrence AJ, Hannan AJ. Positive environmental modification of depressive phenotype and abnormal hypothalamic-pituitary-adrenal axis activity in female C57BL/6J mice during abstinence from chronic ethanol consumption. Front Pharmacol. 2013;4:93.
- Xu X, Pang TY, Hannan AJ. A Tale of Two Maladies? Pathogenesis of Depression with and without the Huntington's Disease Gene Mutation. Front Neurol. 2013;4:81.
- Pang TY, Renoir T, Du X, Lawrence AJ, Hannan AJ. Depression-related behaviours displayed by female C57BL/6J mice during abstinence from chronic ethanol consumption are rescued by wheel-running. Eur J Neurosci. 2013;37:1803-10.
- Pang TY, Hannan AJ. Enhancement of cognitive function in models of brain disease through environmental enrichment and physical activity. Neuropharmacology. 2013;64:515-28.
- Du X, Leang L, Mustafa T, Renoir T, Pang TY, Hannan AJ. Environmental enrichment rescues female-specific hyperactivity of the hypothalamic-pituitary-adrenal axis in a model of Huntington's disease. Transl Psychiatry. 2012;2:e133.
- Renoir T, Pang TY, Hannan AJ. Effects of environmental manipulations in genetically targeted animal models of affective disorders. Neurobiol Dis. 2013;57:12-27.
- Pang TY, Du X, Zajac MS, Howard ML, Hannan AJ. Altered serotonin receptor expression is associated with depression-related behavior in the R6/1 transgenic mouse model of Huntington's disease. Hum Mol Genet. 2009;18:753-66.
- Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7:697-709.
Epigenetics and Neural Plasticity Laboratory
The Neural Plasticity Laboratory investigates gene-environment interactions and experience-dependent plasticity in the healthy and diseased brain, using a variety of experimental approaches. This includes research using a model of Huntington’s disease (HD), a tandem repeat disorder, where we are following up our discoveries regarding the beneficial effects of environmental enrichment (enhanced cognitive stimulation and physical activity) and exercise, as well as depression and dementia-like symptoms associated with abnormalities of brain plasticity. Furthermore, we recently discovered that chronic stress can accelerate onset of HD, and are investigating these neurotoxic effects of stress in HD and other brain disorders.
Many neurological and psychiatric disorders have their origins in abnormal maturation of the brain, including the billions of neurons exquisitely connected by trillions of synapses. We are also investigating how genetic and environmental factors combine to cause specific disorders of brain development and cognition, including schizophrenia and autism spectrum disorders (ASD). We are interested in the mechanisms whereby specific genes regulate maturation of the brain and are dynamically regulated by interaction with the environment in conditions like ASD and schizophrenia.
Our research links data at behavioural and cognitive levels to underlying cellular and molecular mechanisms. We use a variety of behavioural tools, including automated touchscreen testing of cognition and high-throughput data analysis of vocalization and communication, that are directly translatable to clinical tests. We are establishing the extent to which experience-dependent plasticity, including adult neurogenesis and synaptic plasticity, can modulate these behavioural and cognitive endophenotypes, in models with targeted genome editing. This cellular level of understanding is linked, in turn, to molecular mechanisms, including epigenetics, transcriptomics and proteomics.
Based on this research, and the identification of key target molecules, we are also exploring the concept of ‘enviromimetics’, therapeutics that mimic or enhance the beneficial effects of cognitive stimulation and physical exercise. One goal is to develop such therapeutic agents to help reduce the personal and societal burdens of devastating brain disorders such as schizophrenia, HD and dementia.
All Projects by this LabInvestigation of paternal influence on offspring mental healthUtilising Touchscreen technology for preclinical modeling of attention in autism spectrum disorderInvestigating social communication in the Neuroligin 3 mouse model of AutismInvestigating the inherited paternal influence on offspring cognition and behaviourExperience-dependent plasticity modulating cognitive deficits in schizophreniaGene-environment interactions modulating dementia and depression in a tandem repeat disorder
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.