Epilepsy and Emphasis Type="Italic"Tsc2/Emphasi

Authors: Robert Waltereit Birte Japs Miriam Schneider Petrus J de Vries Dusan Bartsch

Publish Date: 2010/10/07

Volume: 41, Issue: 3, Pages: 364-372

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Abstract

There is a strong association between autism spectrum disorders ASD epilepsy and intellectual disability in humans but the nature of these correlations is unclear The monogenic disorder Tuberous Sclerosis Complex TSC has high rates of ASD epilepsy and cognitive deficits Here we used the Tsc2 +/− Eker rat model of TSC and an experimental epilepsy paradigm to study the causal effect of seizures on learning and memory and social behavior phenotypes Status epilepticus was induced by kainic acid injection at P7 and P14 in wildtype and Tsc2 +/− rats At the age of 3–6 months adult rats were assessed in the open field light/dark box fear conditioning Morris water maze novel object recognition and social interaction tasks Learning and memory was unimpaired in naïve Tsc2 +/− rats and experimental epilepsy did not impair any aspects of learning and memory in either wildtype or Tsc2 +/− rats In contrast rearing in the open field novel object exploration and social exploration was reduced in naïve Tsc2 +/− rats Seizures induced anxiety and social evade and reduced social exploration and social contact behavior in wildtype and Tsc2 +/− rats Our study shows that Tsc2 haploinsufficiency and developmental status epilepticus in wildtype and Tsc2 +/− rats independently lead to autisticlike social deficit behaviors The results suggest that the gene mutation may be sufficient to lead to some social deficits and that seizures have a direct and additive effect to increase the likelihood and range of autisticlike behaviorsThis work was supported by research grants from Tuberöse Sklerose Deutschland to RW and Deutsche Forschungsgemeinschaft SFB 636 to DB The authors would like to thank Lena Wendler for excellent technical support and Dr Mathias Zink for help with an initial experiment

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