Regulation of TrkA and ChAT expression in developing rat basal forebrain

Evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons

Yiwen Li, D. M. Holtzman, L. F. Kromer, D. R. Kaplan, J. Chua-Couzens, D. O. Clary, B. Knusel, W. C. Mobley

Research output: Contribution to journalArticle

190 Citations (Scopus)

Abstract

TrkA is a receptor tyrosine kinase whose activation transduces NGF signaling. TrkA expression has been demonstrated in NGF-responsive adult basal forebrain cholinergic neurons (BFCNs). Several lines of evidence have suggested that endogenous NGF plays a role in the development and differentiation of these neurons. We examined TrkA expression during development. TrkA mRNA and protein were present in basal forebrain neurons during the entire postnatal period; the distribution of neurons bearing these markers was identical to that for those containing choline acetyltransferase (CHAT) mRNA, suggesting that, as in the adult, TrkA gene expression is localized to BFCNS. The expression of TrkA and ChAT followed a very similar temporal pattern, suggesting regulation by the same factor(s). We discovered that NGF administration in vivo activated TrkA receptors, and increased both TrkA and ChAT mRNA; conversely, anti-NGF infusions suppressed expression of both genes. These results suggest that endogenous NGF regulates expression of TrkA and ChAT. Finally, while NGF infusion increased the size of developing BFCNs, NGF antibodies inhibited the normal developmental increase. The results are evidence that endogenous NGF acts on developing BFCNs to enhance gene expression and cellular differentiation.

Original languageEnglish
Pages (from-to)2888-2905
Number of pages18
JournalJournal of Neuroscience
Volume15
Issue number4
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Cholinergic Neurons
Nerve Growth Factor
Gene Expression
Neurons
Messenger RNA
trkA Receptor
Basal Forebrain
Choline O-Acetyltransferase
Receptor Protein-Tyrosine Kinases
Antibodies

Keywords

  • basal forebrain cholinergic neurons (BFCNs)
  • ChAT
  • development
  • NGF
  • NGF antiserum
  • NGF receptor
  • TrkA

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Regulation of TrkA and ChAT expression in developing rat basal forebrain : Evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons. / Li, Yiwen; Holtzman, D. M.; Kromer, L. F.; Kaplan, D. R.; Chua-Couzens, J.; Clary, D. O.; Knusel, B.; Mobley, W. C.

In: Journal of Neuroscience, Vol. 15, No. 4, 01.01.1995, p. 2888-2905.

Research output: Contribution to journalArticle

Li, Y, Holtzman, DM, Kromer, LF, Kaplan, DR, Chua-Couzens, J, Clary, DO, Knusel, B & Mobley, WC 1995, 'Regulation of TrkA and ChAT expression in developing rat basal forebrain: Evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons', Journal of Neuroscience, vol. 15, no. 4, pp. 2888-2905.
Li, Yiwen ; Holtzman, D. M. ; Kromer, L. F. ; Kaplan, D. R. ; Chua-Couzens, J. ; Clary, D. O. ; Knusel, B. ; Mobley, W. C. / Regulation of TrkA and ChAT expression in developing rat basal forebrain : Evidence that both exogenous and endogenous NGF regulate differentiation of cholinergic neurons. In: Journal of Neuroscience. 1995 ; Vol. 15, No. 4. pp. 2888-2905.
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