glucagon-like-peptide-1 and Epilepsy

Epilepsy is a common neurological condition induced by losing equilibrium of different pathway as well as neurotransmitters that affects over 50 million people globally. Furthermore, long-term administration of anti-seizure medications has been associated with psychological adverse effects. Also, epilepsy has been related to an increased prevalence of obesity and called type 2 diabetes mellitus. On the other hand, GLP-1 receptors are located throughout the brain, including the hippocampus, which have been associated to majority of neurological conditions, such as epilepsy and psychiatric disorders. Moreover, the impact of different GLP-1 analogues on diverse neurotransmitter systems and associated cellular and molecular pathways as a potential therapeutic target for epilepsy and associated comorbidities has piqued curiosity. In this regard, the anticonvulsant effects of GLP-1 analogues have been investigated in various animal models and promising results such as anticonvulsants as well as cognitive improvements have been observed. For instance, GLP-1 analogues like liraglutide in addition to their possible anticonvulsant benefits, could be utilized to alleviate mental cognitive problems caused by both epilepsy and anti-seizure medication side effects. In this review and growing protective function of GLP-1 in epilepsy induced by disturbed neurotransmitter pathways and the probable mechanisms of action of GLP-1 analogues as well as the GLP-1 receptor in these effects have been discussed.

Topics: Animals; Anticonvulsants; Diabetes Mellitus, Type 2; Epilepsy; Glucagon-Like Peptide 1; Glucagon-Like Peptide-1 Receptor; Humans; Hypoglycemic Agents; Neuroprotective Agents; Neurotransmitter Agents

Epilepsy is one of the most prevalent neurological disorder affecting more than 50 million people worldwide. Numerous studies have suggested that an imbalance in glutamatergic (excitatory) and GABAergic (inhibitory) neurotransmitter system is one of the dominating pathophysiological mechanisms underlying the occurrence and progression of seizures. Further, this alteration in GABAergic and glutamatergic system disrupts the delicate balance of other neurotransmitters system in the brain. Emerging strides have documented the protective role of GLP-1 signaling on altered neurotransmitters signaling in Epilepsy and associated co-morbidities. GLP-1 is neuropeptide and synthesized by preproglucagon (PPG) neurons in the brain. GLP-1 receptors are widely distributed throughout the brain including hippocampus (CA3 and CA1 region) and implicated in various neurological disorders like Epilepsy. A complete understanding of alteration in neurotransmitters signaling will provide essential insight into the basic pathogenic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Presently, treatment of epilepsy is palliative in nature, providing only symptomatic relief to patients. The apparent or traditional approach of treating epileptic subjects with anti-epileptic drugs is associated with variety of adverse effects. Therefore, alternative approaches that can restore altered neurotransmitter signaling are being tried and adopted. Present review is an attempt to highlight the emerging protective role of GLP-1 signaling on altered neurotransmitters signaling in epilepsy. Authors have made significant efforts to discuss effect of various GLP-1 analogs on various neurotransmitters system and associated molecular and cellular pathways as a potential drug target for the management of epilepsy and associated co-morbidities. This article is part of the Special Issue entitled 'Metabolic Impairment as Risk Factors for Neurodegenerative Disorders.'

Topics: Animals; Epilepsy; Glucagon-Like Peptide 1; Humans; Neurotransmitter Agents

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.

Topics: Animals; Comorbidity; Epilepsy; gamma-Aminobutyric Acid; Glucagon-Like Peptide 1; Glutamic Acid; Glutathione; Kindling, Neurologic; Liraglutide; Male; Mice; Nitrites; Pentylenetetrazole