CAN DEVELOPMENTAL, BEHAVIOURAL AND BIOCHEMICAL AND MOLECULAR PARAMETERS PREDICT LEVEL OF SUSCEPTIBILITY TO EPILEPTIC SEIZURES IN SUBJECTS WITH ASD: INSIGHT FROM A RAT MODEL OF ASD
Proceedings for Annual Meeting of The Japanese Pharmacological Society
Introduction In the study, we want to evaluate the association between developmental abberations, behavioural, biochemical and molecular alterations and their association with seizure susceptibility in a rat model of ASD Materials and method The study was conducted in ASD rodent model and was induced by injecting Valproic acid 600mg per kg to pregnant dams on 12.5 days of pregnancy. Total of 12 control and 48 ASD male pups were used in the study. Both cases and controls were subjected to
... subjected to developmental monitoring, neurobehavioural assessments three chamber sociability test, rota rod, Morris water maze, biochemical MDA, GSH level, molecular parameters TNFalpha, IL1beta, BDNF level by ELISA, histopathological examination and IHC for receptor expression GABAA beta and 5HT. Result Seizure score was more in the ASD group 0.67,0.188 compared to control 3.35,0.18 group p less than 0.001. In the control group 58.3percent had mild seizure susceptibility and rest were normal. In the ASD group, 31.25percent mild, 47.91percent moderate and 20.83 percent had high seizure susceptibility p less than 0.05. Among ASD animals, TST stranger chamber cumulative duration was significantly higher in the animals with higher seizure susceptibility p less than 0.001. Animals with very high susceptibility moderate and high group-exhibited significantly less strange chamber cumulative duration when compared to mildly susceptible group p less than 0.01. Among ASD animals, MDA level was highest in the highly susceptible group compared to moderately susceptible group p equal to 0.003, BDNF, IL1beta and TNFalpha levels were higher in the highly susceptible group p less than 0.01 when compared to the mild and moderately susceptible group. BDNF level was higher in the high and moderately susceptible group p less than 0.001 when compared to the mildly susceptible group. IHC revealed alteration in receptor expression in hippocampus between the ASD and control group. Different level of expression was noted between ASD animals with different seizure susceptibility categories. Conclusion Therefore, study reveals that level of social interaction, different molecular and biochemical markers MDA, TNFalpha, IL1beta and BDNF level can serve as predictive biomarkers for development of epilepsy in patients with ASD.