Effects of GLP-1 Receptor Activation on a Pentylenetetrazole—Kindling Rat Model

Brain Sciences

OsamaA. Abulseoud¹  Mohamed El-Mesery²  Mohamed El-Shafey³  GhadaM. Helal⁴  AbdelazizM. Hussein⁵  Mohamed Eldosoky⁵  KhaledM. Abbas⁶  AmrN. Ali⁶ 

[1] Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, National Institutes of Health, Biomedical Research Center, Baltimore, MD 21224, USA;Department of Biochemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt;Department of Human Anatomy, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;Department of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;Faculty of Medicine, Mansoura University, Mansoura 35516, Egypt;

关键词: pentylenetetrazole;    epilepsy;    Hsp70;    LC3;    caspase-3 and β-catenin;   

DOI  :  10.3390/brainsci9050108

来源: DOAJ

【 摘 要 】

Objectives: To study the possible anti-seizure and neuroprotective effect of glucagon like peptide 1 (GLP1) analogue (liraglutide) in a pentylenetetrazole (PTZ) induced kindled rat model and its underlying mechanisms. Methods: Thirty Sprague Dawley rats were allocated into 3 equal groups; i) Normal group: normal rats received normal saline, ii) PTZ (kindling) group: received PTZ (50 mg/Kg intraperitoneally (i.p.)) every other day for 2 weeks and iii) PTZ + GLP1 group: same as the PTZ group but rats received liraglutide (75 µg/kg i.p. daily) for 2 weeks before PTZ injection. Seizure severity score, seizure latency and duration were assessed. Also, the expression of caspase-3 (apoptotic marker) and β-catenin (Wnt pathway) by western blotting, markers of oxidative stress (GSH, CAT and MDA) by biochemical assay and the expression of LC3 (marker of autophagy) and heat shock protein 70 (Hsp70) by immunostaining were assessed in hippocampal regions of brain tissues. Results: PTZ caused a significant increase in Racine score and seizure duration with a significant decrease in seizure latency. These effects were associated with a significant increase in MDA, β-catenin, caspase-3, Hsp70 and LC3 in brain tissues (p < 0.05). Meanwhile, liraglutide treatment caused significant attenuation in PTZ-induced seizures, which were associated with significant improvement in markers of oxidative stress, reduction in LC3, caspase-3 and β-catenin and marked increase in Hsp70 in hippocampal regions (p < 0.05). Conclusion: Activation of GLP1R might have anticonvulsant and neuroprotective effects against PTZ-induced epilepsy. These effects could be due to suppression of oxidative stress, apoptosis and autophagy and upregulation of Hsp70.

【 授权许可】

Unknown