Dados do Trabalho

Título

BONE MARROW MESENCHYMAL STEM CELLS MODULATE THE GENE EXPRESSION OF T-TYPE CALCIUM CHANNEL CACNA1I IN EPILEPTOGENESIS

Introdução

Temporal Lobe Epilepsy (TLE) is a prevalent condition characterized by the abnormal activity of specific neuronal populations, generating typical clinical manifestations, such as recurrent and spontaneous seizures. One of its etiologies is by a modification called calcium channelopathy, which leads to anomalous neuronal intrinsic function. Due to traditional drug treatment limitations, bone marrow mesenchymal stem cells (BM-MSCs) therapy appears as an alternative because of its immunoregulatory and differentiating potentials, increasing synaptic efficiency and decreasing epileptogenesis.

Objetivo

This experimental study investigated BM-MSCs effects on the gene expression of T-type voltage-dependent calcium channels CACNA1I (Cav 3.3) in the context of Pilocarpine-induced TLE rat models.

Método

With this aim, BM-MSCs were extracted from Wistar rats, cultured and transplanted by intranasal (IN) and intravenous (IV) routes. Afterwards, the animals were separated into control and epileptic groups and euthanized 1 and 7 days after treatment. An analysis of the gene expression was conducted by real-time polymerase chain reaction. It showed that BM-MSCs could alter CACNA1I expression in the animal’s brains.

Resultados

Results, as follows, reported that, at 1-day post-transplant, the Pilocarpine group treated with BM-MSCs, compared to the untreated Pilocarpine group, had a negative CACNA1I expression in most evaluated structures for both routes. This suggests that MSCs led to a reduction in glutamatergic signaling, with no N-methyl-D-aspartate receptor and Cav 3.3 activation. Additionally, at 7 days post-transplant, there was an increase in relative expression in all treated groups for both administration routes, suggesting that MSCs might be regulating the surrounding microenvironment in order to increase the extracellular amount of calcium, what would favor the change of the pattern of CACNA1I gene expression. Furthermore, the findings of Cav 3.3 lower expression in the amygdala and the hippocampus corroborate that these channels are not vastly present in these structures.

Conclusão

Overall, it is noteworthy that BM-MSCs were able to modulate gene expression in a pilocarpine-induced epileptic brain, raising the hypothesis that Cav 3.3 may be a therapeutic target for treating epilepsy.

Palavras-chave

temporal lobe epilepsy; channelopathy; mesenchymal stem cells.