TRPM2 ion channel is involved in the aggravation of cognitive impairment and down regulation of epilepsy threshold in pentylenetetrazole-induced kindling mice

Abstract

Epilepsy is one of the most common neurological conditions. Recent findings suggest that one of the mechanisms promoting its existence is calcium influx. The transient receptor potential melastatin type 2 channel (TRPM2) is a Ca2+-permeable cation channel that contributes to cell apoptosis; its possible signaling pathway is the PARP1/BNIP3/AIF/Endo G pathway that may be related to epilepsy. The aim of this study was to investigate the TRPM2 channel’s involvement in epilepsy and how it works. We also explored the possible role of the TRPM2 channel on cognitive ability and emotion in epilepsy. To accomplish our goals, we used different animal epilepsy models to study the effect of the TRPM2 channel on epilepsy. The results showed that the knockout (KO) of the TRPM2 gene might play a protective role in epilepsy. Considering the advantages attributed to pentylenetetrazole (PTZ)-induced kindling mouse model, we used the model for the following assessments: 1. to observe changes in cognition and anxiety between wild type (WT) mice and TRPM2-KO mice with the recognition of new things trial and elevated plus-maze; 2. to determine the expression of apoptosis-associated proteins (PARP1, BNIP3, AIF, and Endo G) using Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot; 3. to observe neurons pathologic damages and astrocyte activation in each group. The main findings of our study were: (a) TRPM2-KO had a protective effect on epilepsy; (b) TRPM2-KO improved spatial memory deficits overtime during epilepsy, but it did not improve anxiety; (c) the protective effect probably occurred via the PARP1 downstream signaling pathway; (d) TRPM2-KO could ameliorate epilepsy-induced hippocampal pathological damages and weaken astrocyte activation. These findings may provide a new approach for the treatment of epilepsy and early intervention.