Exendin-4 improves behaviorial deficits via GLP-1/GLP-1R signaling following partial hepatectomy

Autor: Zhe Li, Hong Ma, Paul F. White, Xuezhao Cao, Xi-Jia Sun, Yong Cui, Yongjian Zhou, Xiaohan Xu, Yanhua Jiang
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Agonist
endocrine system
medicine.medical_specialty
medicine.drug_class
Hippocampus
Morris water navigation task
Hippocampal formation
Neuroprotection
Glucagon-Like Peptide-1 Receptor
Open field
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Postoperative Cognitive Complications
Glucagon-Like Peptide 1
Internal medicine
medicine
Animals
Hepatectomy
Cognitive Dysfunction
Molecular Biology
Neuroinflammation
Glycogen Synthase Kinase 3 beta
Behavior
Animal
biology
business.industry
General Neuroscience
digestive
oral
and skin physiology
NF-kappa B
Rats
Neuroprotective Agents
030104 developmental biology
Endocrinology
Synaptophysin
biology.protein
Exenatide
Neurology (clinical)
business
hormones
hormone substitutes
and hormone antagonists
030217 neurology & neurosurgery
Signal Transduction
Developmental Biology
Zdroj: Brain Research. 1706:116-124
ISSN: 0006-8993
DOI: 10.1016/j.brainres.2018.11.007
Popis: Recent studies indicate that glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonists exhibit neurotrophic and neuroprotective effects. The aim of this study was to explore whether the GLP-1R agonist exendin-4 can alter surgery-induced behavioral deficits and exert neuroprotective effects via the activation of the hippocampal GLP-1/GLP-1R pathway. 120 male Sprague-Dawley rats (aged 18–20 months old) were randomly divided into four groups: control group, exendin-4 group, surgery group, and surgery + exendin-4 group. The animals received either exendin-4 (5 µg/kg/day) or saline intra-peritoneally for 14 days, and then were subjected to partial hepatectomy 24 h after the last injection. Behavioral changes were evaluated with Morris Water Maze and Open field testing on postoperative days 7 and 14. The levels of IL-1β, NF-κB, Iba-1, Synaptophysin, GLP-1/GLP-1R, GSK-3β, p-GSK-3β (Ser9), p-Tau (Ser396), and p-Tau (Ser202/199) in the hippocampus were measured at the same time point. Surgical trauma induced an exacerbated spatial learning and memory impairment, increased the levels of depressive performance, and enhanced hippocampal NF-κB and IL-1β expression in the aged rats on postoperative day 7. A corresponding decline in GLP-1R was also found following surgical challenge on postoperative day 7. Exendin-4 treatment partly reversed surgery-induced postoperative behavioral impairment, downregulated the levels of NF-κB and IL-1β, ameliorated tau hyperphosphorylation and enhanced the activity of p-GSK-3β (Ser9). Together, the downregulation of GLP-1R exacerbated surgery-induced behavior deficits. Exendin-4 treatment attenuated these effects by inhibiting neuroinflammation and tau hyperphosphorylation. These findings suggest that pretreatment with exendin-4 is a potential adjuvant for preventing surgery-induced behavioral deficits.
Databáze: OpenAIRE
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