Mas Receptor Agonism Attenuates Seizures in a Pentylenetetrazole Kindling Model of Experimental Epilepsy in Mice
Year: 2026
Type: preprint
Abstract: To investigate the effects of the Mas receptor (MasR) agonist AVE 0991 on seizure parameters, anxiety-like behavior, and learning-memory functions in a pentylenetetrazole (PTZ)-induced epilepsy model in mice, as well as its impact on MasR, NR2B, and BDNF mRNA expression levels. Seventy-one male Swiss albino mice were used. A chronic kindling model was induced with PTZ (37 mg/kg, i.p.). Following the kindling procedure, animals were assigned to four groups: naïve control, PTZ control (saline), and AVE 0991 at 3 mg/kg or 10 mg/kg. ECoG electrodes were implanted, and AVE 0991 or saline was administered either as a single dose (30 min before PTZ) or daily for 14 days. Seizure severity, first myoclonic jerk latency, generalized seizure latency and duration, spike count during generalized seizures, and total spike number were assessed. After long-term administrations, behavioral evaluations were conducted using the open field test, elevated plus maze, and Y-maze test. Cortical and hippocampal tissues were collected for qPCR analysis of MasR, NR2B, and BDNF mRNA expression. While acute single-dose administration of AVE 0991 failed to alter seizure parameters, long-term AVE 0991 (10 mg/kg) administration reduced seizure severity and spike activity, and prolonged seizure latencies. It also attenuated PTZ-induced anxiety-like behavior and cognitive impairment. Molecular analyses showed that AVE 0991 increased MasR mRNA expression in the cortex and hippocampus and suppressed the PTZ-induced pathological upregulation of NR2B and BDNF mRNA expression. It is suggested that MasR-targeted therapies may hold therapeutic potential in epilepsy, warranting further investigation.
Source: Research Square
Institutions: Ondokuz Mayıs University, Ordu University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7208819745