title: Expression of neuronal-NOS in developing basal forebrain cholinergic neurons: regulation by NGF.
abstract: Nerve growth factor (NGF) acts through the receptor tyrosine kinase trkA to serve as a trophic factor for cholinergic neurons in the medial septal nucleus and vertical limb of the diagonal band. We have previously shown that the neuronal isoform of nitric oxide synthase (NOS) is selectively expressed in a large fraction of trkA-expressing cholinergic neurons in these brain regions in the adult rat, and that NGF induces the expression of neuronal-NOS in these cells. Herein, we show that: 1) neuronal-NOS is also localized to these neurons in the developing septum; 2) the expression of neuronal-NOS is regulated in the developing medial septal nucleus and vertical limb of the diagonal band; 3) neuronal-NOS regulation parallels that for other markers of basal forebrain cholinergic neuron differentiation, such as cholineacetyltransferase; and 4) NGF infusion in the postnatal period induces robust increases in neuronal-NOS mRNA and in NOS activity in the basal forebrain. Taken together with earlier findings, our results suggest that neuronal-NOS has a role in the differentiation and mature function of septal cholinergic neurons. Through enhancing neuronal-NOS synthesis, endogenous NGF is likely to regulate NO functions in vivo.
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA. holtzman@neuro.wustl.edu
authors.forename: D M
authors.initials: DM
authors.lastname: Holtzman
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Chua-Couzens
authors.forename: H
authors.initials: H
authors.lastname: Xia
authors.forename: D S
authors.initials: DS
authors.lastname: Bredt
authors.forename: W C
authors.initials: WC
authors.lastname: Mobley
mesh_terms: D000110:Acetylcholinesterase / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics*; D016548:Prosencephalon / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020917:Receptor, trkA / Q000235:genetics
chemical_list: D009414:Nerve Growth Factors; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase; D020917:Receptor, trkA; D000110:Acetylcholinesterase