Ischemia-induced changes in glucagon-like peptide-1 receptor and neuroprotective effect of its agonist, exendin-4, in experimental transient cerebral ischemia

• Published in: Journal of neuroscience research Vol. 89; no. 7; pp. 1103 - 1113
• Main Authors: Hyun Lee, Choong, Yan, Bingchun, Yoo, Ki-Yeon, Choi, Jung Hoon, Kwon, Seung-Hae, Her, Song, Sohn, Youdong, Hwang, In Koo, Cho, Jun Hwi, Kim, Young-Myeong, Won, Moo-Ho
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.07.2011
• Subjects: Animals; Brain Infarction - drug therapy; Brain Infarction - prevention & control; Brain Ischemia - drug therapy; Brain Ischemia - metabolism; delayed neuronal death; Disease Models, Animal; exendin-4; Gerbillinae; Glucagon-Like Peptide-1 Receptor; Hypoglycemic Agents - pharmacology; Male; microglial activation; Neuroprotective Agents - pharmacology; Peptides - therapeutic use; Receptors, Glucagon - agonists; Receptors, Glucagon - metabolism; Reperfusion Injury - drug therapy; Reperfusion Injury - metabolism; transient cerebral ischemia; Venoms - therapeutic use
• ISSN: 0360-4012; 1097-4547; 1097-4547
• DOI: 10.1002/jnr.22596

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. © 2011 Wiley‐Liss, Inc.