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Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.

ABSTRACT: Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSC function, which impairs adult hippocampal neurogenesis in the long term.

SUBMITTER: Sierra A

PROVIDER: S-EPMC4443499 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.

Sierra Amanda A Martín-Suárez Soraya S Valcárcel-Martín Roberto R Pascual-Brazo Jesús J Aelvoet Sarah-Ann SA Abiega Oihane O Deudero Juan J JJ Brewster Amy L AL Bernales Irantzu I Anderson Anne E AE Baekelandt Veerle V Maletić-Savatić Mirjana M Encinas Juan M JM

Cell stem cell 20150501 5

Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could acce ...[more]

PMID: 25957904

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Dataset Information

Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.

Publications

Neuronal hyperactivity accelerates depletion of neural stem cells and impairs hippocampal neurogenesis.

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