Blockade of L-type voltage-gated Ca channel inhibits ischemia-induced neurogenesis by down-regulating iNOS expression in adult mouse.
Neurogenesis in the adult mammalian hippocampus may contribute to repairing the brain after injury. The signals that regulate neurogenesis in the dentate gyrus following ischemic stroke insult are not well known. We have previously reported that inducible nitric oxide synthase (iNOS) expression is necessary for ischemia-stimulated neurogenesis in the adult dentate gyrus. Here, we show that mice subjected to 90 min of middle cerebral artery occlusion (MCAO) significantly increased the number of new neurons and up-regulated iNOS expression in the dentate gyrus. Blockade of the L-type voltage-gated Ca(2+) channel (L-VGCC) prevented neurogenesis in the dentate gyrus and subventricular zone (SVZ), and down-regulated iNOS expression in the dentate gyrus after cerebral ischemia. This study suggests that Ca(2+) influx through L-VGCC is involved in ischemia-induced neurogenesis by up-regulating iNOS expression.
Luo
Chun Xia
CX
Department of Pharmacology, School of Pharmacy, Nanjing Medical University, China.
Zhu
Xin Jian
XJ
Zhang
Ai Xia
AX
Wang
Wei
W
Yang
Xiao Min
XM
Liu
Shu Hong
SH
Han
Xiao
X
Sun
Jin
J
Zhang
Shu Gang
SG
Lu
Youming
Y
Zhu
Dong Ya
DY
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018891:Dentate Gyrus / Q000503:physiopathology*; D004110:Diltiazem / Q000494:pharmacology; D015536:Down-Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020768:Middle Cerebral Artery; D009416:Nerve Regeneration / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009553:Nimodipine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D004110:Diltiazem