Open AccessSigma‐1 Receptor Knockout Impairs Neurogenesis in Dentate Gyrus of Adult Hippocampus Via Down‐Regulation of NMDA Receptors
Author(s) -
Sha Sha,
Qu WeiJun,
Li Lin,
Lu ZiHong,
Chen Lei,
Yu WenFeng,
Chen Ling
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12129
Subject(s) - dentate gyrus , neurogenesis , nmda receptor , hippocampus , neuroscience , sigma 1 receptor , receptor , knockout mouse , chemistry , medicine , biology , agonist
Summary Aims This study investigated the influence of sigma‐1 receptor (σ 1 R ) deficiency on adult neurogenesis. Methods We employed 8‐week‐old male σ 1 R knockout (σ 1 R −/− ) mice to examine the proliferation and differentiation of progenitor cells, and the survival and neurite growth of newborn neurons in hippocampal dentate gyrus ( DG ). Results In comparison with wild‐type ( WT ) littermates, the numbers of 24‐h‐old B rd U + cells and K i67 + cells in σ 1 R −/− mice increased, while the number of 28‐day‐old B rd U + cells decreased without changes in proportion of B rd U + / N eu N + cells and B rd U + / GFAP + cells. The neurite density of newborn neurons was slightly reduced in σ 1 R −/− mice. In DG granular cells, N ‐methyl‐ d ‐aspartate ( NMDA )‐activated current ( I NMDA ) and phosphorylation of NMDA receptor ( NMDA r) NR 2 B were reduced in σ 1 R −/− mice without the alteration of NR 2 B expression and membrane properties compared to WT mice. The NR 2 B antagonist abolished the difference in I NMDA between σ 1 R −/− mice and WT mice. The application of NMDA r agonist in σ 1 R −/− mice prevented the over‐proliferation of cells and reduction in newborn neurons, but it had no effects on the hypoplastic neurite. The administration of NMDA r antagonist in WT mice enhanced the cell proliferation and depressed the survival of newborn neurons. Conclusion The σ 1 R deficiency impairs neurogenesis in DG through down‐regulation of NMDA rs.