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Regulation of later neurogenic stages of adult‐derived neural stem/progenitor cells by L ‐type C a 2+ channels
Author(s) -
Teh Daniel B. L.,
Ishizuka Toru,
Yawo Hiromu
Publication year - 2014
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12158
Subject(s) - neural stem cell , progenitor cell , progenitor , stem cell , neuroscience , physics , biology , microbiology and biotechnology
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 C a 2+ channels ( LTCC ) which regulate the intracellular C a 2+ ‐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, PZ 5, which was derived from adult rat hippocampus. Although undifferentiated PZ 5 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 PZ 5 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 β III ‐tubulin and MAP 2 was reduced by Nimo but increased by BayK or FPL . At an earlier period of differentiation (e.g. day 4), the fraction of PZ 5 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.