NOS induction by NGF in basal forebrain cholinergic neurones: evidence for regulation of brain NOS by a neurotrophin.
Nerve growth factor (NGF) acts through trkA receptors to serve as a trophic factor for cholinergic neurones in the medial septal nucleus (MSN) and vertical limb of the diagonal band (VDB). Herein, we show that brain nitric oxide synthase (NOS), which synthesizes the neuromodulator nitric oxide, is selectively expressed in a large fraction of trkA-containing neurones in the MSN and VDB. Axotomy of these neurones gave evidence that NOS expressing cholinergic neurones innervate the hippocampus. NGF infusion induced a robust, specific increase in NOS expression in basal forebrain cholinergic neurones. These results indicate that brain NOS can be regulated by a neurotrophic factor and suggest that NGF influences forebrain function by regulating production of nitric oxide as well as acetylcholine.
Holtzman
D M
DM
Department of Neurology, University of California, San Francisco, 505 Parnassus Ave, San Francisco, CA, 94143, USA.
Kilbridge
J
J
Bredt
D S
DS
Black
S M
SM
Li
Y
Y
Clary
D O
DO
Reichardt
L F
LF
Mobley
W C
WC
D000818:Animals; D015152:Blotting, Northern; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology*; D004790:Enzyme Induction / Q000187:drug effects; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley
D009414:Nerve Growth Factors; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase