Dexamethasone induces hypertrophy of developing medial septum cholinergic neurons: potential role of nerve growth factor.
Glucocorticoid hormones influence neuronal plasticity during development; however little is known about the mechanisms of this trophic activity. Because glucocorticoids increase nerve growth factor (NGF) synthesis in selected brain areas and NGF plays a role in the development of basal forebrain cholinergic neurons, we tested the hypothesis that glucocorticoids may foster maturation of the cholinergic phenotype during postnatal development via the induction of NGF biosynthesis. The synthetic glucocorticoid dexamethasone (DEX) was injected systemically (0.5 mg/kg, s.c.) once a day for 1 week in 7-d-old (P7) rats. DEX elicited an increase in NGF mRNA and protein levels in the cerebral cortex and hippocampus as well as specific NGF responses, such as TrkA tyrosine phosphorylation in the septum, choline acetyltransferase (ChAT) and p75 neurotrophin receptor (p75NTR) immunoreactivity, and a relative number of cholinergic neurons in the medial septum. To examine whether the effect of DEX is age-related, we treated 1- and 14-d-old rats with DEX for 1 week. DEX increased NGF expression in rats treated from P1 to P8 but not in those treated from P14 to P21. The age-related increased expression of NGF correlated with the induction of ChAT immunoreactivity in the medial septum. Moreover, in the spinal cord, neither NGF nor ChAT levels were increased by DEX, suggesting that the glucocorticoid-mediated changes seen in the basal forebrain are associated with specific NGF responses. Our data suggest that by increasing NGF levels, glucocorticoids may play a role in the maturation of postnatal cholinergic neurons.
Shi
B
B
Department of Cell Biology, Division of Neurobiology, Georgetown University, School of Medicine, Washington, DC 20007, USA.
Rabin
S J
SJ
Brandoli
C
C
Mocchetti
I
I
D000367:Age Factors; D000818:Animals; D000906:Antibodies; D048429:Cell Size / Q000187:drug effects; D002795:Choline O-Acetyltransferase / Q000032:analysis / Q000276:immunology; D002799:Cholinergic Fibers / Q000737:chemistry* / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D005938:Glucocorticoids / Q000494:pharmacology*; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012686:Septal Nuclei / Q000166:cytology* / Q000196:embryology; D013116:Spinal Cord / Q000166:cytology / Q000201:enzymology
D000906:Antibodies; D005938:Glucocorticoids; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; D016222:Fibroblast Growth Factor 2; D003907:Dexamethasone; D002795:Choline O-Acetyltransferase; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA