Glucosamine promotes seizure activity via activation of the PI3K/Akt pathway in epileptic rats

•Different doses of glucosamine confer different effects on epileptic activity.•Glucosamine (2.0 g/kg) may activate p-Akt Ser473 signaling to aggravate epileptic activity.•Prolonged glucosamine administration should be carefully considered in patients with epilepsy. Glucosamine is an amino monosaccharide with a small molecular weight and has a protective effect against various neurological diseases including multiple sclerosis and encephalomyelitis. Interestingly, low-dose glucosamine has exhibited anti-epilepsy activity. Recent studies have shown that the activation of the protein kinase B (Akt) signaling pathway may promote epilepsy. Glucosamine can increase the level of Akt phosphorylation in the brain tissue, which may aggravate epilepsy. Hence, we speculate that a higher dose of glucosamine may aggravate epilepsy via AKT signaling. To investigate the effect of glucosamine on the behavior and electrophysiology of epileptic rats through PI3K/Akt pathway. Glucose (2.0 g/kg) and glucosamine (0, 0.5, 1.0, and 2.0 g/kg) were added to 2 mL of drinking water, respectively. An acute seizure rat model of lithium-pilocarpine and PTZ-kindling were constructed to observe the effects of different doses of glucosamine on epileptic behavior and hippocampal electrical activity. Meanwhile, the changes in Akt were detected by western blot. Epileptic seizures were induced by a single dose of pilocarpine or PTZ and 2.0 g/kg of glucosamine significantly prolonged the duration and severity of epileptic seizures, enhanced hippocampal electrical activity energy density, and increased phosphorylated AKT levels. A glucosamine dose of 2.0 g/kg also significantly increased the total onset energy density. Furthermore, 2.0 g/kg glucosamine facilitated the development of the chronic PTZ-kindling process. Glucosamine may exacerbate acute and chronic epileptic seizures via activation of the PI3K/Akt pathway in rats with experimental epilepsy.