NMDA receptor and iNOS are involved in the effects of ginsenoside Rg1 on hippocampal neurogenesis in ischemic gerbils.
OBJECTIVE
Transient global ischemia increases neurogenesis in the dentate gyrus of adult rodents and this may have a functional relevance. The aim of the present study was to explore the possible mechanisms underlying the effects of ginsenoside Rg1 on hippocampal neurogenesis in adult gerbils suffered from global ischemia.


METHODS
Experimental groups include: Group 1: sham operation; Group 2: sham operation + MK-801 (3 mg/kg); Group 3: ischemia only; Group 4: ischemia + MK-801; Group 5: ischemia + Rg1 (5 mg/kg); Group 6: ischemia + Rg1 + MK-801. At the tenth day after ischemia, six gerbils from Groups 1, 3 and 5 were killed and the activity of inducible nitric oxide synthase (iNOS) in the cortex and hippocampus was measured. The rest animals were given bromodeoxyuridine (BrdU, 50 mg/kg) every 4 hours for 12 hours at the tenth day after ischemia and perfused 24 hours after the last injection of BrdU. Immunohistochemistry was performed to identify proliferating cells in the dentate gyrus.


RESULTS
Ginsenoside Rg1 increased the magnitude of ischemia induced proliferation of hippocampal progenitor cells and enhanced the activity of iNOS in both the hippocampus and cortex. Systematic injection of MK-801 completely blocked the proliferation increasing effect of Rg1.


CONCLUSIONS
Ginsenoside Rg1 increases neurogenesis after transient global ischemia. The mechanisms underlying this effect may involve activation of iNOS activity and N-methyl-D-aspartate (NMDA) receptors in the brain.
Shen
Lihong
L
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. lihong@neuro.hfh.edu
Zhang
Juntian
J
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005849:Gerbillinae; D036145:Ginsenosides / Q000737:chemistry / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology*; D007511:Ischemia / Q000188:drug therapy / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism*; D038081:Organogenesis / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D036145:Ginsenosides; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D052247:Nitric Oxide Synthase Type II; D001973:Bromodeoxyuridine; C035054:ginsenoside Rg1