glucagon-like-peptide-2 and Dementia

This review focuses on the anti-dementia and antidepressant-like effects of peptides including glucagon-like peptide (GLP)-1, GLP-2, neuromedin U (NmU), and oxytocin, and the intranasal delivery of these peptides to the brain. Intracerebroventricularly administered GLP-1, NmU, and oxytocin improved impairment of learning and memory in mice treated with lipopolysaccharide or β-amyloid protein. GLP-1 also improved impairment of learning and memory in juvenile diabetes model rats. On the other hand, GLP-2 exhibited antidepressant-like effects in mice during the forced-swim test, which were associated with 5-HT

Topics: Administration, Intranasal; Animals; Brain; Dementia; Depression; Drug Delivery Systems; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Mice; Neuropeptides; Oxytocin; Peptides; Rats

Glucagon-like peptide 2 (GLP-2) is derived from the proglucagon gene expressed in the intestines, pancreas and brain. Our previous study showed that GLP-2 improved lipopolysaccharide-induced memory impairments. The current study was designed to further investigated the potential of GLP-2 in memory impairment induced by intracerebroventricular administration of streptozotocin (ICV-STZ) in mice, which have been used as an animal model of sporadic Alzheimer's disease (AD). STZ was administered on alternate days (Day-1 and Day-3) in order to induce dementia in male ddY mice. ICV-STZ-treated mice were administered GLP-2 (0.6 μg/mouse, ICV) for 5 days from 14 days after the first ICV administration of STZ. In these mice, we examined spatial working memory, the biochemical parameters of oxidative stress, or neurogenesis. The GLP-2 treatment restored spatial working memory in ICV-STZ-treated mice. ICV-STZ-treated mice showed markedly increased thiobarbituric acid reactive species (TBARS) and decreased glutathione (GSH) levels, and GLP-2 significantly restored these ICV-STZ-induced changes. GLP-2 also significantly restored neurogenesis in the subgranular zone of the dentate gyrus in ICV-STZ-treated mice. We herein demonstrated that GLP-2 significantly restored ICV-STZ-induced memory impairments as well as biochemical and histopathological alterations, and accordingly, propose that the memory restorative ability of GLP-2 is due to its potential to reduce oxidative stress.

Topics: Animals; Brain; Dementia; Disease Models, Animal; Glucagon-Like Peptide 2; Male; Memory Disorders; Mice; Neurogenesis; Neuroprotective Agents; Oxidative Stress; Spatial Memory; Streptozocin; Thiobarbituric Acid Reactive Substances