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Saturday, May 17, 2008
Champagne Terrace/Bordeaux (Novotel London West)
Background: Chemicals including thalidomide (THAL) and valproic acid (VPA) are known to induce autism when taken at early gestational stage in human. We have previously established autism model rats by exposing THAL or VPA to embryonic (E) day 9 rats (Pediatr Res, 52; 576: 2002, Int J Dev Neurosci, 23; 287: 2005). Migration disorder of serotonergic (5-HT) neurons was observed in the adult.
Objectives: Our objectives were to elucidate whether abnormalities of 5-HT neuronal development are also observed even in the embryonic stage. Molecular basis of 5-HT developmental abnormalities were also elucidated.
Methods: THAL, VPA, or vehicle was orally administered to early pregnant rats corresponding to human embryopathy related to autism, and then, embryos were dissected out for anti-serotonin immunohistochemistry. Embryos were also analyzed for the expression of certain genes including sonic hedgehog (shh), a modulator for serotonergic development, using whole mount in situ hybridization and real time PCR technique.
Results: Dramatic delay of serotonergic development was observed in the embryos of autism model rats. Expression of shh were perturbed in the embryos of autism rats.
Conclusions: These results indicate that two potential autism-inducing teratogens, THAL and VPA, may disrupt early 5-HT neuronal development in the embryos through the perturbation of shh signal pathway, and thus may cause irreversible changes observed in the adult.
Supports: Long-range Research Institute from the Japan Chemical Industry Association and Grants-in-Aid for Scientific Research (C) of Japan Society for the Promotion of Science.
Objectives: Our objectives were to elucidate whether abnormalities of 5-HT neuronal development are also observed even in the embryonic stage. Molecular basis of 5-HT developmental abnormalities were also elucidated.
Methods: THAL, VPA, or vehicle was orally administered to early pregnant rats corresponding to human embryopathy related to autism, and then, embryos were dissected out for anti-serotonin immunohistochemistry. Embryos were also analyzed for the expression of certain genes including sonic hedgehog (shh), a modulator for serotonergic development, using whole mount in situ hybridization and real time PCR technique.
Results: Dramatic delay of serotonergic development was observed in the embryos of autism model rats. Expression of shh were perturbed in the embryos of autism rats.
Conclusions: These results indicate that two potential autism-inducing teratogens, THAL and VPA, may disrupt early 5-HT neuronal development in the embryos through the perturbation of shh signal pathway, and thus may cause irreversible changes observed in the adult.
Supports: Long-range Research Institute from the Japan Chemical Industry Association and Grants-in-Aid for Scientific Research (C) of Japan Society for the Promotion of Science.