Glucagon-like Peptide-2 Receptor Expression In The Central Nervous System In Mice

Objective: Glucagon like peptide 2 (GLP-2), deriving from the prog- lucagon peptides (PGDP), is the product of proglucagon gene expression. It is a single-chain polypeptide containing 33 amino acid residues of the amino acid sequence 126-158 of proglucagon, and its molecular weight is about 3900 Da. GLP-2 was found in recent years, and could specifically promote growth of intestinal mucosa and repair after injury. GLP-2 receptor (GLP-2R) is a member of the G protein coupling receptor superfamily. GLP-2R has seven transmembrane domains, and has a high homology with the GLP-1, glucagon and GIP (glucose-dependent insulinotropic polype- ptide) receptors. GLP-2R was mainly expressed in the gastrointestinal tract and brain. Proliferative and protective effects of GLP-2 on the intestinal mocosa have been investigated in recent years, but the effect of GLP2 on the central nervous system and the distribution of GLP-2R in the nervous system remain unclear. The purpose of this study is to examine the distribution of GLP-2R in the central nervous system in mice, and provide a proof of GLP-2 in the central nervous systems.Methods: Male and healthy BALB/C mice were randomly divided into control group and the GLP-2 treatment group. GLP-2 was given intra- cerebrally by dose of 250μg/kg, twice a day for three consecutive days, and mice in control group were injected intracerebrally by normal saline. Mice in two groups were fasted for 16-18h, then sacrificed for collecting the samples of the cerebral cortex, hypothalamus, brain stem, cerebellum and hippocampus, and L4-6 spinal cord. The samples of tissues were conven- tionally fixed, paraffin-embedded, slice-making for HE staining and immu- nohistochemistry (SABC).Results: The results showed that GLP-2R was expressed in many areas of the central nervous system in mice, and the expression levels were as follows: spinal cord, cerebral cortex, hypothalamus, brain stem, hippo- campus, cerebellum; and expression of GLP-2R in cerebral cortex and hypothalamus in GLP-2 treatment group were significantly increased caom- pared with control group (P<0.05); pyramidal cell layer of the cerebral cortex in GLP-2 treated mice were significantly thickened, and the number and volume of pyramidal cells were increased, compared with the control group,. These results suggest that GLP-2 receptor is widely expressed in central nervous system, particularly in the cerebral cortex, hypothalamus, and spinal cord. GLP-2 is a brain-gut peptide, not only performing in the gastrointestinal tract, but also play a possible role in the central nervous system.Conclusions:1. GLP-2 receptor is widely expressed in central nervous system, particularly in the cerebral cortex, hypothalamus, and spinal cord.2. GLP-2 promote the expression of GLP-2R in cerebral cortex and hypothalamus in the mouse, thicken pyramidal cell layer of the cerebral cortex, and increase the number and volume of pyramidal cells.