Dados do Trabalho

Título

Evaluation of SLC12A5 (KCC2) gene expression promoted by mesenchymal stem cells in the treatment of experimental epilepsy

Introdução

Temporal lobe epilepsy (TLE), recognized by the presence of spontaneous and recurrent seizures, has a high rate of refractoriness, in addition to a high incidence. Currently, regarding its epidemiology, it is known that, concerning its incidence, about 65 million people are affected by this disease. Therefore, the study of cellular mechanisms and new therapies are extremely important for the understanding of TLE. A mechanism already studied on the loss of electrochemical homeostasis, related to seizures, is associated with lower expression of a cation-chloride co-transporter, called KCC2.

Objetivo

The present work sought to demonstrate the effect that intravenous mesenchymal stem cell (MSCs) transplantation promotes in the context of TLE induced by the pilocarpine model in rats on the gene expression levels of the KCC2 cation-chloride cotransporter.

Método

To perform this, MSCs were extracted from donor rats, cultured and transplanted intravenously into control rats and animals induced to status epilepticus with pilocarpine. The animals were euthanized at 1 and 7 days after transplantation, and then molecular analysis by real-time polymerase chain reaction was performed on isolated brain structures.

Resultados

As a result, MSCs were able to alter the amount of transcript in the brain of animals: where a trend of gene expression decreased 1 day after transplantation and an increase in 7 days after transplantation were observed. After 7 days of transplantation, the transcript levels were modified in relation to the control group, and it was observed that during this period the expression of KCC2 was higher in relation to day 1, that is, closer to the insult.

Conclusão

These results suggest that, in the acute period, its expression is attenuated, and the treatment tends to accentuate the transcription of the SLC12A5 gene in periods more distant from the insult. The temporal factor can play an important role, where 1-day post-transplant is the closest to the first seizure. In addition, loss of KCC2 function decreases chloride release and there is difficulty in inhibiting GABAergic inhibition, which can result in hyperexcitability of neuronal circuits. In conclusion, MSCs are able to modulate the expression of cation-chloride KCC2 cotransporters in animals induced to status epilepticus.

Palavras-chave

KCC2, temporal lobe epilepsy, mesenchymal stem cells