INTRAVENTRICULAR ADMINISTRATION OF BDNF INCREASES NEUROPEPTIDE EXPRESSION IN NEWBORN RAT-BRAIN

Brain-derived neurotrophic factor (BDNF) specifically enhances and mai ntains the expression of neuropeptide Y (NPY) and somatostatin (SOM) i n cultured neocortical neurons (Nawa et al., 1993). In this article, w e examined its effects in vivo on neuropeptide expression in various b rain regions by injecting BDNF into the cerebroventricle of newborn ra ts. Repeated administration (2 x) of BDNF increased contents of NPY-li ke 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 s ignificant increase was also observed in immunoreactivity for somatost atin (SOM), enkephalin (ENK), and cholecystokinin (CCK). mRNA for NPY, SP, and SOM was similarly upregulated in the anterior neocortex, sugg esting that BDNF enhances peptide synthesis rather than inhibiting pep tide release or degradation. Among the brain regions examined, however , peptidergic responses to BDNF were different with respect to their s patial distribution and time course. Induction of SP-LI, NPY-LI, and S OM-LI around the injection site was most pronounced in cortical layers II/III, layers IV-VI, and layer VI, respectively. Peptidergic immunor eactivity was also enhanced in other brain regions ipsilateral to the injection site, for example, NPY-LI in the hippocampus, thalamic nucle i, and striatum, and SOM-LI in the striatum. A single injection of BDN F elevated SP-LI to a plateau level within 12 hr while NPY-LI and SOM- LI reached maximum levels at 48 hr, and then air returned to control l evels at 68 hr. In contrast, the same dose of NGF had no influences on the neuropeptide levels at 48 hr. These observations suggest that BDN F regulates the development of neuropeptide expression in the CNS in a plastic manner.