Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice

http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = Neurochem Res (2016) 41:17411750 DOI 10.1007/s11064-016-1890-4

http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = ORIGINAL PAPER

http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = http://crossmark.crossref.org/dialog/?doi=10.1007/s11064-016-1890-4&domain=pdf

Web End = Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice

Prashant Koshal1 Puneet Kumar1

Received: 31 August 2015 / Revised: 14 March 2016 / Accepted: 17 March 2016 / Published online: 26 March 2016 Springer Science+Business Media New York 2016

Abstract GLP-1 play important role in neuroprotection and GLP-1 receptor decit mice showed decreased seizure threshold and increased cognitive impairment. Therefore, study was premeditated to investigate the effect of liraglutide (GLP-1 analogue) on cornel kindling epilepsy induced co-morbidities in mice. Corneal kindling was induced by electrical stimulation (6 mA, 50 Hz, 3 s); twice daily for 13 days. Liraglutide (75 and 150 lg/kg) and phenytoin (20 mg/kg) were administered in corneal kindled groups. On day 14, elevated plus maze, passive shock avoidance paradigms were performed, and on day 15, retention was taken. On day 16 tail suspension test were performed. On 20th day challenge test was performed with same electrical stimulation and retention was observed on elevated plus maze and passive avoidance paradigm. Animal were sacriced on 21st day for biochemical (LPO, GSH, and nitrite) and neurochemical (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Electrical stimulation by corneal electrode for 13 days developed generalized clonic seizures, increased cognitive impairment, oxidative stress and neurochemical alteration in mice brain. Co-treatment with liraglutide (75 and 150 lg/kg)

signicantly prevented the seizure severity, restored behavioural activity, oxidative stress and restored the altered level of neurotransmitters observed in corneal kindled mouse.

Keywords Neurotransmitters Depression Cognitive

impairment Epilepsy GLP-1 Liraglutide Oxidative

stress

AbbreviationsCA Corpus ammonisDA DopamineDOPAC 3,4-Dihydroxyphenylacetic acid GLP-1 Glucagon like peptide-1 GLP-1Rs Glucagon like peptide-1 receptors HVA Homovanillic acidNE Norepinephrine5-HIAA 5-Hydroxyindoleacetic acid

Introduction

Epilepsy is one of the most privileged neurological disorder, characterized by persistent unprovoked seizure which results from abnormal and synchronous neuronal discharge within the brain [1]. Around 40 million people worldwide, 3 million in USA, and 23 million people in Asia are affected by the epilepsy [24]. Epileptic seizure is an unexpected imbalance...