| Abstract No.: | C-G3182 |
| Country: | Canada |
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| Title: | ALTERATIONS IN GENE EXPRESSION AND BEHAVIOUR IN RESPONSE TO MATERNAL CHALLENGE |
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| Authors/Affiliations: | 2 Florence Roullet; 1 Florence Roullet*; 4 Marie Gadziola; 5 Marie Gadziola; 4 Denys Denys deCatanzaro; 4 Paul Faure; 3 Jane Foster;
1 Brain Body Institue and McMaster University, department of Psychiatry and Behavioural Neuroscience; 2 Brain Body Institute and Department of Psychiatry & Behavioural Neurosciences, McMaster Univers; 3 Brain Body Institute and Department of Psychiatry & Behavioural Neurosciences, McMaster University; 4 Department of Psychology, McMaster University; 5 McMaster, Department of sychology, Hamilton, ON, Canada.
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| Content: | Environmental factors have been associated with neurodevelopmental illnesses including autism. For example, epidemiological studies reveal that in utero exposure to an anti-epileptic drug, valproic acid (VPA) can induce fetal valproate syndrome that has been linked to autism. In rodents, maternal exposure to VPA during pregnancy has been suggested as an animal model for autism as offpring of VPA challenge dam show deficits in autistic-like behaviours.
Objectives and Material and Methods
In our laboratory we have demonstrated that VPA pups show alterations in post-natal growth and development, deficitis in olfactory discrimination and social behaviour early in development, and sex-related differences in anxiety-like behaviour in adult. Here we examined dopaminergic-related gene expression and plasticity related gene expression, including brain derived neurotrophic factor (BDNF) and 2 subunits of the NMDA receptor, NR2a and NR2b. We extended our analysis of early developmental behaviours to include ultrasonic volcalizations (USVs), used by pups to signal the dams to retrieve them when they are removed from the nest.
Results
In situ hybridization experiments revealed alterations in gene expression in adult brain of VPA mice including lower cortical expression of BDNF mRNA and a sex-related difference in dopaminergic receptor D2R mRNA expression in the striatum but no difference in NR2a and NR2b mRNA expression in the cortex. VPA mice also exhibited a higher number of call (vocalizations) and an increased call period but a similar call duration in USVs tested on postnatal day 7.
Conclusion
Our gene expression results demonstrate that there are long-term alterations at the level of gene expression in mice demonstrating autistic-like behaviours. The USV analyses demonstrate behavioural alterations occur early in life suggesting that the neurobiological changes in these mice also occurs in an early developmental window. The next important step is to examine molecular changes early in life that accompany these behavioural alterations.
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