Submission ID 92765
| Poster Code | HR-P-75 |
|---|---|
| Title of Abstract | Embryonic ablation of Atrx in excitatory neurons results in memory deficits and autistic-like behaviours in adult mice |
| Abstract Submission | Neurodevelopmental disorders affect 1 in 12 Canadians and pose large social and medical challenges. Overlapping features and often comorbidities in diagnosis occur in patients, suggesting an overlap in regions of the brain that have developed atypically. Previous reports show mutations in chromatin remodeling proteins are prevalent in patients of intellectual disability and autism. Furthermore, 70% of patients with autism also have intellectual disability. In this study, we examine the function of the gene alpha thalassemia mental retardation, X-linked (ATRX), a chromatin remodeling protein. Hypomorphic mutations in ATRX result in ATR-X-syndrome, a disorder characterized by severe intellectual disability and autistic features. Understanding the mechanistic role(s) ATRX plays in the brain is crucial to identify possible points of therapeutic intervention. I hypothesize that ATRX is required from early stages of excitatory neuron development to achieve typical learning and memory and prevent autistic-like behaviours. Mice lacking ATRX specifically in excitatory neurons from embryonic day 11.5 were generated to study effects of loss of ATRX in differentiated excitatory neurons early during brain development. Loss of ATRX in excitatory neurons embryonically resulted in a decrease in contextual fear memory, along with a prominent hyperactive and aggressive phenotype in adult mice. Mutant mice also exhibited repetitive behaviours (over-grooming) and a significant startle response suggesting acoustic hypersensitivity compared to control littermates. Magnetic resonance imaging (MRI) analysis revealed decreased relative brain volumes in the hippocampus, cerebellum and white matter regions, whereas regions of the cortex and thalamus had significant increased relative brain volumes. We conclude that neuronal ATRX plays a critical role during early brain development in excitatory neurons to prevent memory deficits and autistic features. MRI data suggests that loss of ATRX early in brain development results in atypical brain structure and possible disruption of the neuronal circuitry. |
| Please indicate who nominated you | Anatomy and Cell Biology Graduate Committee- Western University |
| What Canadian Institutes of Health Research (CIHR) institute is your research most closely aligned? | Neurosciences, Mental Health and Addiction |
| What Canadian Institutes of Health Research (CIHR) pillar of health research does your research fall under? | Health systems services |
| PDF of abstract | Abstract Quesnel Katherine.pdf 2023-01-31 at 18:28:19 |
| Presenter and Author(s) | Katherine Quesnel Katherine Quesnel Nicole Martin-Kenny Jacob Ellegood Jason Lerch Nathalie Berube |
