Dados do Trabalho

Título

Modulation of NKCC1 gene expression performed by mesenchymal stem cells used as treatment in experimental epilepsy

Introdução

Temporal lobe epilepsy (TLE) is characterized by rhythmic and synchronized firing of neuronal populations that lead to spontaneous and recurrent seizures. Worldwide, it is estimated that around 65 million people are affected by this disorder. About ⅓ of the individuals affected by this disorder are refractory to traditional pharmacological therapies, therefore seeking therapeutic alternatives is extremely important.

Objetivo

Therapy with mesenchymal stem cells (MSCs) appears as a possible new treatment, due to its great potential for tissue differentiation, immunoregulation, ability to modulate diseased niches and neuroprotective activity. In epilepsy, several cellular components are involved, and knowledge about their participation can provide strategies and understanding about the functional role of BM-MSCs in acting on their beneficial effects. One of these components are the Na-K-Cl 1 cotransporters (NKCC1), responsible for the uptake of Na +, K + and 2Cl-, which allow the extrusion of chloride and GABAergic depolarization. The present study aimed to evaluate the effect that BM-MSCs promote on gene expression of the cation-chloride cotransporter NKCC1 in the context of induced TLE in rats.

Método

For this purpose, MSCs were extracted from long bones of Wistar rats, expanded in culture and subsequently prepared for transplantation intravenously (IV). At the same time, the animals were divided into two groups: control and epileptic, being euthanized 1 and 7 days after the intervention. After euthanasia, the animals had their brains removed and brain structures were selected for gene analysis by Real-time polymerase chain reaction.

Resultados

As a result of gene expressions in the amygdala, hippocampus, entorhinal cortex, prefrontal cortex and brain of rats, it is verified that the expression of NKCC1 increased in all groups treated with MSCs via IV compared to control groups in 1 day and 7 days after treatment.

Conclusão

Several studies demonstrate that, in epilepsy, there are variations in the amount of NKCC1 transcription, which is very important for electrical and ionic homeostasis in neurons. As we could see in the experiment, the MSCs therapy by IV can modify the expression of this cotransporter. Therefore, we raise the observation that MSCs, due to their multipotentiality and regulatory properties, could help in rebalancing, aiding in the resumption of homeostasis through the modification of NKCC1 expression, which would be directly linked to TLE mechanisms.

Palavras-chave

temporal lobe epilepsy, gene expression, cátion-chloride cotransporter