Feeding, activity, and body temperature following 6-hydroxydopamine lesions in diabetes (db/db) mice.

Reductions in central catecholamines produced by intraventricular injections of 6-hydroxydopamine (6-OHDA) cause weight loss and decreased plasma glucose in diabetes (db/db) mice. The present study examined the effects of this treatment in short-term (64-day) and long-term (120-day) survival groups of female diabetes (C57 BL/KsJ-db/db) and lean mice. Phenotypically heterozygotes (db/m) and homozygotes (m/m) were used as controls. Diabetes Ss treated with 6-OHDA decreased food intake, lost weight, and maintained a lower weight than vehicle-treated controls until vehicle-treated Ss began to enter the terminal stages of the syndrome, indicated by a loss of body weight. Diabetes Ss given 6-OHDA lost weight despite reduced body temperatures and activity levels. Blood glucose levels were always lower in 6-OHDA than in ad lib fed vehicle-treated db/db Ss. The 6-OHDA treatment also improved pancreatic islet granulation. Pair feeding vehicle-treated with 6-OHDA-treated db/db Ss did not halt weight gain in the vehicle-treated group. However, measurement of carcass fat indicated similar losses in db/db-6-OHDA Ss and vehicle-treated Ss when the vehicle group was pair-fed with lean controls. Treatment with 6-OHDA produced long-term improvement in the diabetes syndrome, but the decreased body weight of the 6-OHDA-treated diabetes Ss could not be completely accounted for by changes in food intake or energy expenditure. (43 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Intraventricular administration of BDNF increases neuropeptide expression in newborn rat brain

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.