Reduced abnormal integration of adult-generated granule cells does not attenuate spontaneous recurrent seizures in mice

Abstract

Epileptic seizures lead to aberrant hippocampal neurogenesis, including increased proliferation of neural progenitors and abnormal integrations of newly generated granule cells – hilar ectopic granule cells (EGCs), mossy fiber sprouting (MFS), and hilar basal dendrites (HBDs). Previous results from ablating hippocampal neurogenesis after acute seizures have been controversial with regards to the development of spontaneous recurrent seizures (SRSs). While ablation of hippocampal newborn cells was effective, a sufficient decrease of subsequent abnormal integrations in chronically epileptic hippocampus was not well-established in these studies. Evaluations of the role of aberrant neurogenesis in epileptogenesis were therefore inconclusive. In this study, we ablated the hippocampal neurogenesis by methylazoxymethanol acetate (MAM) treatment both before and after pilocarpine induced status epilepticus (SE). We found that an overall ablation of newborn granule cells and a protracted delay after the cell ablation are required to eliminate subsequent abnormal integrations, including EGCs, MSF and HBDs. However, there were no alterations in frequency, duration and severity of chronic seizures were demonstrated following this regime. The current findings provide novel evidences that an overall decrease of abnormal integrations via cell ablation cannot exert significant effects on the development of SRSs at least in the model used in this study.