title: Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia.
abstract: Glucagon-like peptide-1 receptor (GLP-1R) protects against neuronal damages in the brain. In the present study, ischemia-induced changes in GLP-1R immunoreactivity in the gerbil hippocampal CA1 region were evaluated after transient cerebral ischemia; in addition, the neuroprotective effect of the GLP-1R agonist exendin-4 (EX-4) against ischemic damage was studied. GLP-1R immunoreactivity and its protein levels in the ischemic CA1 region were highest at 1 day after ischemia/reperfusion (I/R). At 4 days after I/R, GLP-1R immunoreactivity was hardly detected in CA1 pyramidal neurons, and its protein level was lowest. GLP-1R protein level was increased again at 10 days after I/R, and GLP-1R immunoreactivity was found in astrocytes and GABAergic interneurons. In addition, EX-4 treatment attenuated ischemia-induced hyperactivity, neuronal damage, and microglial activation in the ischemic CA1 region in a dose-dependent manner. EX-4 treatment also induced the elevation of GLP-1R immunoreactivity and protein levels in the ischemic CA1 region. These results indicate that GLP-1R is altered in the ischemic region after an ischemic insult and that EX-4 protects against ischemia-induced neuronal death possibly by increasing GLP-1R expression and attenuating microglial activation against transient cerebral ischemic damage.
authors.affiliation: Laboratory of Veterinary Pharmacology, College of Veterinary Medicine, Seoul National University, Seoul, South Korea.
authors.forename: Choong Hyun
authors.initials: CH
authors.lastname: Lee
authors.forename: Bingchun
authors.initials: B
authors.lastname: Yan
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Choi
authors.forename: Seung-Hae
authors.initials: SH
authors.lastname: Kwon
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.forename: Youdong
authors.initials: Y
authors.lastname: Sohn
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Jun Hwi
authors.initials: JH
authors.lastname: Cho
authors.forename: Young-Myeong
authors.initials: YM
authors.lastname: Kim
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000188:drug therapy / Q000517:prevention & control; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D000077270:Exenatide; D005849:Gerbillinae; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010455:Peptides / Q000627:therapeutic use*; D018027:Receptors, Glucagon / Q000819:agonists* / Q000378:metabolism*; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism; D014688:Venoms / Q000627:therapeutic use*
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D018696:Neuroprotective Agents; D010455:Peptides; D018027:Receptors, Glucagon; D014688:Venoms; D000077270:Exenatide