Exendin-4 Pretreatment Attenuates Kainic Acid-Induced Hippocampal Neuronal Death
Yu-Jeong Ahn,
Hyun-Joo Shin,
Eun-Ae Jeong,
Hyeong-Seok An,
Jong-Youl Lee,
Hye-Min Jang,
Kyung-Eun Kim,
Jaewoong Lee,
Meong-Cheol Shin,
Gu-Seob Roh
Affiliations
Yu-Jeong Ahn
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Hyun-Joo Shin
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Eun-Ae Jeong
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Hyeong-Seok An
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Jong-Youl Lee
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Hye-Min Jang
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Kyung-Eun Kim
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Jaewoong Lee
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Meong-Cheol Shin
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Gyeongsang National University, Jinju 52828, Korea
Gu-Seob Roh
Bio Anti-Aging Medical Research Center, Department of Anatomy and Convergence Medical Science, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, Korea
Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist that protects against brain injury. However, little is known about the effect of Ex-4 on kainic acid (KA)-induced seizures and hippocampal cell death. Therefore, this study evaluated the neuroprotective effects of Ex-4 pretreatment in a mouse model of KA-induced seizures. Three days before KA treatment, mice were intraperitoneally injected with Ex-4. We found that Ex-4 pretreatment reversed KA-induced reduction of GLP-1R expression in the hippocampus and attenuated KA-induced seizure score, hippocampal neuronal death, and neuroinflammation. Ex-4 pretreatment also dramatically reduced hippocampal lipocalin-2 protein in KA-treated mice. Furthermore, immunohistochemical studies showed that Ex-4 pretreatment significantly alleviated blood–brain barrier leakage. Finally, Ex-4 pretreatment stimulated hippocampal expression of phosphorylated cyclic adenosine monophosphate (cAMP) response element-binding protein (p-CREB), a known target of GLP-1/GLP-1R signaling. These findings indicate that Ex-4 pretreatment may protect against KA-induced neuronal damage by regulating GLP-1R/CREB-mediated signaling pathways.
