Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent andERK-independent mechanisms

Citation
A. Barnea et J. Roberts, Induction of functional and morphological expression of neuropeptide Y (NPY) in cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a requirement for extracellular-regulated kinase (ERK)-dependent andERK-independent mechanisms, BRAIN RES, 919(1), 2001, pp. 57-69
Citations number
49
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
BRAIN RESEARCH
ISSN journal
0006-8993 → ACNP
Volume
919
Issue
1
Year of publication
2001
Pages
57 - 69
Database
ISI
SICI code
0006-8993(20011116)919:1<57:IOFAME>2.0.ZU;2-6
Abstract
Previous studies have demonstrated that brain-derived neurotrophic factor ( BDNF) induces expression of neuropeptide Y (NPY) neurons in aggregate cultu res derived from the fetal rat cortex. Using BDNF induction of NPY producti on and neurite extension of NPY neurons as functional and morphological cri teria, respectively, we addressed the question: Does BDNF activate the extr acellular-regulated kinase (ERK) pathway and if so, is activated (phosphory lated, P)-ERK required for the induction of both the functional and morphol ogical expression of NPY? BDNF led to a rapid (30 min) and sustained (6 h) phosphorylation of ERK. PD98059 (PD, a specific inhibitor of the ERK kinase MEK), drastically inhibited, LY294002 (LY, a specific inhibitor of phospha tidylinositol-3-kinase, PI-3K) partially inhibited, and GF 109203X (GF, a s pecific inhibitor of protein kinase C) did not inhibit phosphorylation of E RK. A 24-h exposure to BDNF led to similar to2-fold increase in the total c ulture content of NPY (similar to 60% of which was secreted and similar to 40% remained in the aggregates) and to an abundance of neurite-bearing NPY neurons. BDNF-induced NPY produced and secreted into the medium was inhibit ed 73% by PD, 52% by LY and not at all by GF. In contrast, BDNF-induced NPY produced and sequestered in the aggregates was not inhibited by any of the se inhibitors, suggesting a role for the ERK pathway in induced secretion o f NPY. PD or LY did not inhibit BDNF-induced abundance of neurite-bearing N PY neurons. K252a (an inhibitor of TrkB-tyrosine kinase) abolished all the effects of BDNF assessed in our cultures. In summary, we demonstrate that T rkB-mediated activation of the ERK pathway is preferentially required for B DNF induction of NPY produced and secreted but not for the induction of the expression of neurite-bearing NPY neurons. Thus, BDNF induction of the fun ctional and morphological expression of NPY is brought about by ERK-depende nt and ERK-independent mechanisms. (C) 2001 Elsevier Science BY All rights reserved.