Nerve growth factor promotes survival of new neurons in the adult hippocampus.
Exogenously provided NGF enhances cognitive performance in impaired rodents and humans and is currently a promising compound for the treatment of dementia. To investigate whether NGF-dependent cognitive improvement may be due in part to increased hippocampal neurogenesis, adult and aged male rats were treated with NGF or vehicle intracerebroventricularly for 6 or 20 days followed by evaluation of cholinergic parameters and hippocampal neurogenesis. We show that NGF increases hippocampal cholinergic activity as rapidly as 3 days after initiation of treatment. NGF treatment for 6 days did not affect proliferation of progenitor cells in the dentate gyrus granule cell layer (GCL). However, continuous NGF infusion enhanced survival of new neurons in the GCL of young adult, but not aged rats. Taken together, these findings suggest that NGF, likely mediated through increased cholinergic tone, promotes neurogenesis in the adult hippocampus, which may relate to the nootropic action of NGF.
Frielingsdorf
Helena
H
Department of Neurosciences, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0624, USA.
Simpson
Daniel R
DR
Thal
Leon J
LJ
Pizzo
Donald P
DP
D000375:Aging / Q000502:physiology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344
D000963:Antimetabolites; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D001973:Bromodeoxyuridine