Regulation of neuronal differentiation by N-methyl-D-aspartate receptors expressed in neural progenitor cells isolated from adult mouse hippocampus.

In vitro culture of neural progenitor cells isolated from adult murine hippocampus according to the Percoll density gradient method resulted in formation of round spheres not immunoreactive to microtubule-associated protein-2 (MAP-2) or glial fibrillary acidic protein in the presence of basic fibroblast growth factor within 12 days in vitro (DIV). Reverse-transcription PCR analysis revealed constitutive expression in these neurospheres of different subunits required for assembly of functional heteromeric N-methyl-D-aspartate (NMDA) receptor channels. Immunocytochemical analysis confirmed expression of NR1, NR2A, and NR2B subunits in neurospheres cultured for 4-12 DIV. Brief (5 min) exposure to NMDA induced marked expression of c-Fos, Fos-B, Fra-2, and c-Jun proteins in neurospheres cultured for 12 DIV 2 hr later. The NMDA receptor antagonist dizocilpine markedly inhibited expression of both c-Jun and c-Fos proteins in NMDA-exposed neurospheres. Sustained exposure to NMDA not only markedly inhibited neurosphere formation by 12 DIV when exposed from 4-12 DIV, but also resulted in facilitation of subsequent differentiation of neurospheres exposed to all-trans retinoic acid to cells immunoreactive to both neuron-specific enolase and neuronal nuclei, in addition to MAP-2, as revealed by Western blot and immunocytochemistry analyses. These results suggest that functional heteromeric NMDA receptors may be expressed constitutively in neural progenitor cells before differentiation to play a crucial role in commitment and differentiation to neurons in adult murine hippocampus.

Kitayama T ，Yoneyama M ，Tamaki K ，Yoneda Y ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

Counteraction by repetitive daily exposure to static magnetism against sustained blockade of N-methyl-D-aspartate receptor channels in cultured rat hippocampal neurons.

Hirai T ，Taniura H ，Goto Y ，Tamaki K ，Oikawa H ，Kambe Y ，Ogura M ，Ohno Y ，Takarada T ，Yoneda Y ... -  《JOURNAL OF NEUROSCIENCE RESEARCH》

Effect of NMDA receptor antagonist on proliferation of neurospheres from embryonic brain.

Mochizuki N ，Takagi N ，Kurokawa K ，Kawai T ，Besshoh S ，Tanonaka K ，Takeo S ... -  《NEUROSCIENCE LETTERS》

Promotion of neuronal differentiation through activation of N-methyl-D-aspartate receptors transiently expressed by undifferentiated neural progenitor cells in fetal rat neocortex.

Yoneyama M ，Nakamichi N ，Fukui M ，Kitayama T ，Georgiev DD ，Makanga JO ，Nakamura N ，Taniura H ，Yoneda Y ... -  《-》

In vivo treatment with the K+ channel blocker 4-aminopyridine protects against kainate-induced neuronal cell death through activation of NMDA receptors in murine hippocampus.

Ogita K ，Okuda H ，Watanabe M ，Nagashima R ，Sugiyama C ，Yoneda Y ... -  《NEUROPHARMACOLOGY》