Kainic acid (KA)-induced experimental epilepsy, a model of excitotoxicity, leads to selective neuronal death and synaptic restructuring. We used this model to investigate the effects of neuronal hyperactivation on palmitoyl-protein thioesterase 1 (PPT1), the deficiency of which causes drastic neurodegeneration. Immunological stainings showed that epileptic seizures in adult rats led to a progressive and remarkable increase of PPT1 in limbic areas of the brain. Within 1 week, the maximal expression was observed in CA3 and CA1 pyramidal neurons of the hippocampus. In the surviving pyramidal neurons, PPT1 localized in vesicular structures in cell soma and neuritic extensions. After seizures, colocalization of PPT1 with synaptic membrane marker (NMDAR2B) was enhanced. Further, synaptic fractionation revealed that after seizures PPT1 was readily observed on the presynaptic side of synaptic junction. These data suggest that PPT1 may protect neurons from excitotoxicity and have a role in synaptic plasticity.
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