Gene expression of calcium channel CACNA1H in epileptogenesis can be modulated by mesenchymal stem cells

Abstract

Introduction: Temporal Lobe Epilepsy (TLE) is the most common refractory epilepsy, and it is characterized by abnormal firing of a population of neurons in the brain, and by cognitive deficit1 . This abnormal intrinsic phenomenon can cause deregulation of the T-type calcium channels, increasing neuronal excitability, leading to structural changes in the Central Nervous System2 . Mesenchymal Stem Cells (MSCs) are a therapeutic alternative for the TLE for they can modulate neurotransmitters liberation, reducing neuronal death and increasing neurogenesis3,4,5. The present study analyzed MSCs effects on gene expression of T-type calcium channel CACNA1H in the brain of pilocarpine-induced TLE animal models. Methods: The MSCs were obtained from the bone marrow of Wistar rats, cultured, and transplanted intravenously and intranasally. The animals were separated into the following groups: control and pilocarpine-induced status epilepticus, then they were euthanized 1- and 7-days post-transplant for gene expression analysis. Results: The results show that 1-day post-transplant there was no difference in the CACNA1H gene expression between the MSC-treated pilocarpine groups and the control and untreated pilocarpine groups. Subsequently 7-days posttransplant, the treated groups showed greater expression of the gene in both means of administration. Moreover, there was an increase in CACNA1H gene expression in the prefrontal cortex of the treated pilocarpine group, which makes us conjecture a mechanism of greater need for its transcription in this area. Conclusion: Thus, MSCs were able to modulate the expression of the CACNA1H gene in the brain, increasing its importance as a target for future studies on epilepsy therapies involving cells.