Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline

Abstract

Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that ablation of adult neurogenesis prior to pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis prior to acute seizures is long-lasting as it suppresses chronic seizure frequency for nearly one year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

Intranasal MSC-derived A1-exosomes ease inflammation, and prevent abnormal neurogenesis and memory dysfunction after status epilepticus

“…It is currently unknown whether these anomalies by themselves are adequate to induce spontaneous seizures (48). Nonetheless, their involvement in manifestations of spontaneous seizures after SE has been well documented (49)(50)(51)(52)(53)(54).…”

Mossy Fiber Sprouting in the Epileptic Brain: Taking on the Lernaean Hydra

“…One in particular concerns the impact of antineurogenic treatments on sprouting: specifically, while blocking neurogenesis with methylazoxymethanol acetate (MAM) proved effective at reducing sprouting (in a study by Liu and colleagues [8]), recent studies using transgenic thymidine-kinase and diphtheria toxin-mediated cellablation strategies found no impact on eliminating juvenile and newborn granule cells on mossy fiber sprouting (9,10). Future studies will be needed to resolve these discrepancies.…”

Neurogenesis in Cancun: where science meets the sea

“…Seizure activity can induce robust generation of ectopically localized granule cells in the adult hippocampus. Jenny Hsieh (UT Southwestern Medical Center, Dallas, USA) showed that ablation of adult neurogenesis before pilocarpineinduced seizures in the nestin-TK transgenic mouse line can lead to improved cognitive function and a significant reduction of chronic seizure frequency (Cho et al, 2015). She further presented unpublished data using a chemogenetic approach to determine whether silencing adult-born neuronal activity can result in a reduction of seizure frequency.…”