Impact of Human Chorionic Gonadotropin on Pentylenetetrazol-Induced Seizure Activities in Mice: Modulation of miR-۱۸۱a Expression as a Potential Neuroprotective Mechanism

Introduction: Epilepsy affects millions of people globally, with ۳۰% of patients exhibiting drug resistance, necessitating novel therapies. Human chorionic gonadotropin (hCG), known for neuroprotective effects, has been underexplored in epilepsy despite its role in neuronal survival. Therefore, this study aimed to evaluate hCG’s anticonvulsant potential in a pentylenetetrazole (PTZ)-induced seizure model in male mice and to assess its impact on the hippocampal gene expression of microRNA-۱۸۱a (miR-۱۸۱a), brain-derived neurotrophic factor (BDNF, Bcl-۲-associated X protein (Bax), and B-cell lymphoma ۲ (Bcl-۲). Methods: Male mice (n = ۷ per group) received hCG (۱۵۰۰ IU/kg, intraperitoneal) or saline for ۵ days, followed by PTZ (۸۰ mg/ kg) to induce seizures. Seizure latency was recorded, and hippocampal gene expression was analyzed via real-time polymerase chain reaction. Results: hCG pretreatment significantly delayed seizure onset compared to the PTZ-only group (P < ۰.۰۰۱). No significant changes were observed in miR-۱۸۱a, BDNF, or Bcl-۲ expression (P > ۰.۰۵), while Bax was elevated in PTZ and PTZ+hCG groups (P < ۰.۰۱ and P < ۰.۰۰۱, respectively). Conclusion: hCG’s anticonvulsant effect, likely mediated by N-methyl-D-aspartate receptor inhibition, highlights its therapeutic potential independent of apoptotic or neurotrophic gene modulation. In contrast to the findings of chronic epilepsy models, where miR-۱۸۱a and BDNF alterations are prominent, our results demonstrated a different underlying mechanism. Limitations included the acute model’s limited generalizability and lack of protein-level validation. Accordingly, future studies should explore chronic models and alternative mechanisms, such as oxidative stress pathways. Overall, hCG’s established safety supports its potential as an adjunctive therapy for epilepsy, addressing drug resistance challenges.