NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus.
The production of new neurons declines during adulthood and persists, although at very low levels, in the aged hippocampus. Since neurogenesis in young adults has been related to learning and memory, its reduction may contribute to the age-related impairments in these abilities. Adrenalectomy (ADX) enhances neurogenesis in the aged hippocampus, although it also induces neuronal cell death. Since the administration of an NMDA receptor antagonist enhances neurogenesis in young adult rats without deleterious morphological effects, we have tested whether neurogenesis could be reactivated in aged rats. Our study shows that cell proliferation, cell death, neurogenesis and the number of radial glia-like nestin immunoreactive cells decrease in middle-age (10 months) and remain very low in the aged hippocampus. Injection of the NMDA receptor antagonist to aged rats increases significantly the number of proliferating cells, new neurons and radial glia-like cells in the hippocampus.
Nacher
Juan
J
Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA. nacher@uv.es
Alonso-Llosa
Gregori
G
Rosell
Daniel R
DR
McEwen
Bruce S
BS
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000315:Adrenalectomy; D000375:Aging / Q000502:physiology*; D000818:Animals; D000963:Antimetabolites; D015415:Biomarkers; D001973:Bromodeoxyuridine; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology*; D000089622:Doublecortin Domain Proteins; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D007150:Immunohistochemistry; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins / Q000032:analysis; D009457:Neuroglia / Q000166:cytology; D009474:Neurons / Q000737:chemistry / Q000166:cytology*; D009479:Neuropeptides / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000963:Antimetabolites; D015415:Biomarkers; D000089622:Doublecortin Domain Proteins; C449760:Dpysl3 protein, rat; D018691:Excitatory Amino Acid Antagonists; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; C087755:CGP 43487; D015763:2-Amino-5-phosphonovalerate; D001973:Bromodeoxyuridine