title: Neurochemical modulation involved in the beneficial effect of liraglutide, GLP-1 agonist on PTZ kindling epilepsy-induced comorbidities in mice.
abstract: Epilepsy is a neurological disorder which occurs due to excessive firing of excitatory neurons in specific region of brain and associated with cognitive impairment and depression. GLP-1 has been reported to maintain hyperexcitability of neurons. Therefore, this study was designed to investigate the neuroprotective effect of liraglutide, GLP-1 analogue in PTZ kindling epilepsy-induced comorbidities and neurochemical alteration in mice. Male albino mice were administered PTZ (35 mg/kg) on every alternate day up to 29th days and challenge test was performed on 33rd day. From 1st day liraglutide (75 and 150 µg/kg) and diazepam (3 mg/kg) were administered up to 33rd day, 30 min prior to PTZ treatment. On 30th day animals were trained on elevated plus maze and passive shock avoidance paradigm and retention was recorded on 31st and 33rd day. On 32nd day tail suspension test was performed. Animals were sacrificed on 34th day for biochemical (LPO, GSH, and nitrite) and neurotransmitters (GABA, glutamate, DA, NE, 5-HT and their metabolites) estimation. Chronic treatment with PTZ developed generalized tonic-clonic seizures, reduced cognitive skills, increased oxidative stress and alteration in the level of neurotransmitters. Pre-treatment with liraglutide (75 and 150 μg/kg) significantly prevented the seizure severity, restored behavioural activity, oxidative defence enzymes, and altered level of neurochemicals in mice brain. The protective effect of liraglutide is attributed to restoration of altered level of GABA, glutamate, DA, NE, and 5-HT by the up-regulation of GLP-1Rs in mice brain.
authors.affiliation: Department of Pharmacology, ISF College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, Punjab, 142001, India.
authors.forename: Prashant
authors.initials: P
authors.lastname: Koshal
authors.affiliation: Department of Pharmacology, ISF College of Pharmacy, Ferozepur Road, Ghal Kalan, Moga, Punjab, 142001, India. punnubansal79@gmail.com.
authors.forename: Puneet
authors.initials: P
authors.lastname: Kumar
mesh_terms: D000818:Animals; D015897:Comorbidity; D004827:Epilepsy / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D018698:Glutamic Acid / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D007696:Kindling, Neurologic / Q000187:drug effects*; D000069450:Liraglutide / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D009573:Nitrites / Q000378:metabolism; D010433:Pentylenetetrazole / Q000494:pharmacology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D009573:Nitrites; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D005978:Glutathione; D010433:Pentylenetetrazole
keywords: Catecholamines; Cognitive impairment; Depression; GLP-1; Liraglutide; Oxidative stress