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Journal of Neuroscience, Vol 14, 3751-3765, Copyright © 1994 by Society for Neuroscience
Intraventricular administration of BDNF increases neuropeptide expression in newborn rat brain
H Nawa, MA Pelleymounter and J Carnahan
Beckman Neuroscience Center, Cold Spring Harbor Laboratory, New York, NY 11724.
Brain-derived neurotrophic factor (BDNF) specifically enhances and
maintains the expression of neuropeptide Y (NPY) and somatostatin (SOM) in
cultured neocortical neurons (Nawa et al., 1993). In this article, we
examined its effects in vivo on neuropeptide expression in various brain
regions by injecting BDNF into the cerebroventricle of newborn rats.
Repeated administration (2x) of BDNF increased contents of NPY- like
immunoreactivity (NPY-LI) and substance P (SP)-LI most markedly in the
anterior neocortex by 11- and 24-fold, respectively, in comparison to
values in the animals receiving control injection. A smaller but
significant increase was also observed in immunoreactivity for somatostatin
(SOM), enkephalin (ENK), and cholecystokinin (CCK). mRNA for NPY, SP, and
SOM was similarly upregulated in the anterior neocortex, suggesting that
BDNF enhances peptide synthesis rather than inhibiting peptide release or
degradation. Among the brain regions examined, however, peptidergic
responses to BDNF were different with respect to their spatial distribution
and time course. Induction of SP- LI, NPY-LI, and SOM-LI around the
injection site was most pronounced in cortical layers II/III, layers IV-VI,
and layer VI, respectively. Peptidergic immunoreactivity was also enhanced
in other brain regions ipsilateral to the injection site, for example,
NPY-LI in the hippocampus, thalamic nuclei, and striatum, and SOM-LI in the
striatum. A single injection of BDNF elevated SP-LI to a plateau level
within 12 hr while NPY-LI and SOM-LI reached maximum levels at 48 hr, and
then all returned to control levels at 68 hr. In contrast, the same dose of
NGF had no influences on the neuropeptide levels at 48 hr. These
observations suggest that BDNF regulates the development of neuropeptide
expression in the CNS in a plastic manner.
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