Increasing adult neurogenesis protects mice from epilepsy

Author:

Jain Swati,LaFrancois John J.,Gerencer Kasey,Botterill Justin J.,Kennedy Meghan,Criscuolo Chiara,Scharfman Helen E.ORCID

Abstract

ABSTRACTNeurogenesis occurs in the adult brain in the hippocampal dentate gyrus, an area that contains neurons which are vulnerable to insults and injury, such as severe seizures. Previous studies showed that increasing adult neurogenesis reduced neuronal damage after these seizures. Because the damage typically is followed by chronic life-long seizures (epilepsy), we asked if increasing adult neurogenesis would prevent epilepsy. Adult neurogenesis was selectively increased by deleting the pro-apoptotic geneBaxfrom Nestin-expressing progenitors. Tamoxifen was administered at 6 weeks of age to conditionally deleteBaxin Nestin-CreERT2Baxfl/flmice. Six weeks after tamoxifen administration, severe seizures (status epilepticus; SE) were induced by injection of the convulsant pilocarpine. Mice with increased adult neurogenesis exhibited fewer chronic seizures. Postictal depression was reduced also. These results were primarily female mice, possibly because they were the more affected byBaxdeletion than males, consistent with sex differences inBaxin development. The female mice with enhanced adult neurogenesis also showed less neuronal loss of hilar mossy cells and hilar somatostatin-expressing neurons than wild type females or males, which is notable because these two cell types are implicated in epileptogenesis. The results suggest that increasing adult neurogenesis in the normal adult brain can reduce experimental epilepsy, and the effect shows a striking sex difference. The results are surprising in light of past studies showing that suppressing adult-born neurons can also reduce chronic seizures.

Publisher

Cold Spring Harbor Laboratory

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