F. Marmigere et al., Regulation of brain-derived neurotrophic factor transcripts by neuronal activation in rat hypothalamic neurons, J NEUROSC R, 66(3), 2001, pp. 377-389
Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family
and regulates the survival, differentiation, and maintenance of function i
n different neuronal populations. BDNF is strongly expressed in hypothalami
c neurons, where it exerts long- or short-lasting actions. Because glutamat
e has been associated with regulations of hypothalamic hormones, we examine
d the regulation of the four promoters of the BDNF gene by glutamate in fet
al hypothalamic neurons. The expression levels of BDNF transcripts were inv
estigated using semiquantitative RT-PCR. BDNF protein was determined by enz
yme immunoassay, and BDNF and Trk B (BDNF receptor) gene variations were de
termined by RNAse protection assay. By RT-PCR, we showed that, under basal
conditions, BDNF transcripts from exons I, II, and III but not from IV were
expressed in the hypothalamic neurons. Glutamate increased expression of b
oth the protein and the four transcripts via N-methyl-D-aspartate receptors
, with maximal stimulations after 3 hr of application for exon I and II mRN
As and after 1 hr for exon III and IV mRNAs. Actinomycin D blocked the incr
ease of all transcripts, whereas cycloheximide treatment inhibited stimulat
ion only of exon I and II mRNAs. Trk B. mRNA was rapidly and transiently re
duced after glutamate application. Our results demonstrate that glutamate 1
) regulates BDNF mRNA expression at an early developmental stage in hypotha
lamic neurons and 2) exerts a differential regulation of BDNF transcripts.
(C) 2001 Wiley-Liss, Inc.