Regulation of later neurogenic stages of adult-derived neural stem/progenitor cells by L-type Ca2+ channels

Daniel B.L. Teh, Toru Ishizuka, Hiromu Yawo

    Research output: Contribution to journalArticlepeer-review

    11 Citations (Scopus)

    Abstract

    In the adult hippocampus, new neurons are continuously generated and incorporated into the local circuitry in a manner dependent on the network activity. Depolarization evoked by neurotransmitters has been assumed to activate L-type Ca2+ channels (LTCC) which regulate the intracellular Ca2+-dependent signaling cascades. The process of neurogenesis contains several stages such as proliferation, fate determination, selective death/survival and maturation. Here, we investigated which stage of neurogenesis is under the regulation of LTCC using a clonal line of neural stem/progenitor cells, PZ5, which was derived from adult rat hippocampus. Although undifferentiated PZ5 cells were type 1-like cells expressing both nestin and glial fibrillary acidic protein, they generated neuronal, astrocytic and oligodendrocytic populations in differentiation medium containing retinoic acid. Proliferation of undifferentiated PZ5 cells was dependent on neither the LTCC antagonist, nimodipine (Nimo) nor the LTCC agonists, Bay K 8644 (BayK) or FPL 64176 (FPL), whereas the fraction of neuronal population that expressed both βIII-tubulin and MAP2 was reduced by Nimo but increased by BayK or FPL. At an earlier period of differentiation (e.g. day 4), the fraction of PZ5 cells expressing HuC/D, pan-neuronal marker, was not affected either by the LTCC activation or inhibition. At a later period of differentiation (e.g. day 9), the fraction of dying neurons was decreased by LTCC activation and increased by LTCC inhibition. It is suggested that the LTCC activation facilitates the survival and maturation of immature neurons, and that its inhibition facilitates the neuronal death.

    Original languageEnglish
    Pages (from-to)583-594
    Number of pages12
    JournalDevelopment Growth and Differentiation
    Volume56
    Issue number8
    DOIs
    Publication statusPublished - 2014 Oct 1

    Keywords

    • Death/survival
    • Differentiation
    • L-type Ca channel
    • Neural stem cell
    • Neurogenesis

    ASJC Scopus subject areas

    • Developmental Biology
    • Cell Biology

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