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

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Abstract

GLP-1 play important role in neuroprotection and GLP-1 receptor deficit 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 µg/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 sacrificed 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 μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative stress and restored the altered level of neurotransmitters observed in corneal kindled mouse.

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Abbreviations

CA:

Corpus ammonis

DA:

Dopamine

DOPAC:

3,4-Dihydroxyphenylacetic acid

GLP-1:

Glucagon like peptide-1

GLP-1Rs:

Glucagon like peptide-1 receptors

HVA:

Homovanillic acid

NE:

Norepinephrine

5-HIAA:

5-Hydroxyindoleacetic acid

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  1. Neuropharmacology Division, Department of Pharmacology, ISF College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, Punjab, 142001, India

    Prashant Koshal & Puneet Kumar

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  1. Prashant Koshal
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  2. Puneet Kumar
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Correspondence to Puneet Kumar.

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Koshal, P., Kumar, P. Effect of Liraglutide on Corneal Kindling Epilepsy Induced Depression and Cognitive Impairment in Mice. Neurochem Res 41, 1741–1750 (2016). https://doi.org/10.1007/s11064-016-1890-4

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