Prenatal Testosterone Influence on Reelin Expression in Association with Autism

OBJECTIVES: Autism is the most genetically influenced neuropsychiatric disorder with unknown etiology. Reelin, one of the autism candidate genes plays a major role in neuronal migration during neurodevelopment and in regulation of synaptic plasticity in postnatal period. Autistic patients have decreased levels of reelin in plasma and frontal and cerebellar cortices. Testosterone pathway is suspicious in autism pathogenesis, since increased fetal testosterone correlates with strong autistic traits. Testosterone administration sharply decreases reelin expression in brains of male starlings. Our purpose was to reveal the possible relationship between testosterone pathway and reelin expression in context of autism pathogenesis using rat model. METHODS: Pregnant rats were injected with testosterone. Reelin expression was measured in certain brain areas using real time PCR and immunohistochemistry methods. RESULTS: Reelin expression was decreased in hypothalamus (males) and cerebellum (females) in newborn pups of testosterone treated mothers. In adult offspring of testosterone treated mothers we have observed an opposite pattern. Immunohistochemical analysis has shown the presence of reelin positivity in parietal cortices of control group, whereas no rather than low reelin positivity was observed in parietal cortices of offspring of testosterone treated mothers. CONCLUSION: We can conclude that testosterone may regulate reelin expression in the brain of mammals. However, further studies are needed to focus on this pathway in more details, since this pathway may play an important role in pathogenesis of autistic disorder.