title: Dexamethasone induces TrkA and p75NTR immunoreactivity in the cerebral cortex and hippocampus.
abstract: Nerve growth factor (NGF) plays a crucial role in synaptic plasticity during brain development and adulthood by activating a dual receptor system composed of TrkA and p75 (p75NTR) receptors. Exogenous NGF modulates the expression of both receptors. Little is known about the ability of endogenous NGF to regulate the expression of these receptors in basal forebrain cholinergic terminals. The ability of glucocorticoids to increase NGF expression in the hippocampus prompted us to investigate whether the synthetic glucocorticoid dexamethasone (DEX) increases TrkA and p75NTR expression in NGF-target cholinergic neurons in developing rats. We first examined the effect of DEX on NGF mRNA by in situ hybridization. DEX given systemically (0.5 mg/kg, sc) for 1 week to 7-day-old rats elicited an increase in NGF mRNA levels in the dentate gyrus of the hippocampus and superficial layers II and III of the cerebral cortex. Immunohistochemical analysis of p75NTR and TrkA levels revealed a dramatic increase in p75NTR immunoreactivity (IR) in both basal forebrain and hippocampus and TrkA IR in the hippocampus. Interestingly, in DEX-treated rats more axonal terminals were immunopositive for p75NTR in the hippocampus and cortex, suggesting an increase in p75NTR IR in cell bodies as well as in terminals. Our data indicate that the endogenously produced NGF elicits biological changes similar to those of the exogenously delivered NGF. We suggest that glucocorticoids might regulate and coordinate cholinergic neuronal maturation by increasing the biosynthesis of NGF.
authors.affiliation: Department of Neuroscience, Georgetown University School of Medicine, Washington, DC 20007, USA.
authors.forename: B
authors.initials: B
authors.lastname: Shi
authors.forename: I
authors.initials: I
authors.lastname: Mocchetti
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D017729:Presynaptic Terminals / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism*; D020917:Receptor, trkA / Q000378:metabolism*; D020665:Septum of Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D003907:Dexamethasone; D020932:Nerve Growth Factor; D002795:Choline O-Acetyltransferase; D020917:Receptor, trkA