Nrf2-ARE signaling pathway regulates the expressions of A1R and ENT1 in the brain of epileptic rats

OBJECTIVE: To explore the behavioral changes and the expressions of the A1 receptor (A1R) and balanced nucleoside transporter-1 (ENT1) in the brain of epileptic rats after activating the NF-E2-related factor 2 (Nrf2)-ARE signaling pathway.

MATERIALS AND METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into normal control group, epilepsy group, and t-butylhydroquinone (tBHQ) group, with 10 rats in each group. Lithium-pilocarpine induced epilepsy model in rats was established. The first epileptic latency and seizure frequency within 1 hour were observed in each group using the Racine scoring system. HE (Hematoxylin and Eosin) staining was used to observe the pathological lesions in the brain tissue of each group. The expressions of A1R, ENT1, and relative genes in Nrf2-ARE pathway in rat hippocampus was detected by immunohistochemistry and Western blot.

RESULTS: Compared with rats in epileptic group, the first seizure latency was prolonged and the seizure frequency decreased in tBHQ group (p<0.05). The degree of brain lesions in tHBQ group was lighter than that of epilepsy group. ENT1 expression in rat hippocampus of epileptic group was significantly upregulated than that of normal control group and tBHQ group. Besides, the protein levels of A1R, Nrf2, HO-1, and ARE in rat hippocampus of epilepsy group markedly decreased compared with those of normal control group. However, protein expressions of A1R, Nrf2, HO-1, and ARE proteins in rat hippocampus of tBHQ group were markedly upregulated.

CONCLUSIONS: Activation of the Nrf2-ARE signaling pathway can reduce the pathological damage of rat hippocampal neurons, prolong the latency of seizures, and reduce the degree of epileptic seizure in rats.

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