Everolimus inhibits PI3K/Akt/mTOR and NF-kB/IL-6 signaling and protects seizure-induced brain injury in rats.

Autor: Huang XY; Department of Function Examination, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China. Electronic address: hxyi9966@126.com., Hu QP; Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China. Electronic address: huqpeng6868@163.com., Shi HY; Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China., Zheng YY; Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China., Hu RR; Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China., Guo Q; Department of Pediatrics, The Second Hospital, University of South China, Hengyang, Hunan, 421001, China.
Jazyk: angličtina
Zdroj: Journal of chemical neuroanatomy [J Chem Neuroanat] 2021 Jul; Vol. 114, pp. 101960. Date of Electronic Publication: 2021 Apr 26.
DOI: 10.1016/j.jchemneu.2021.101960
Abstrakt: Background: Epilepsy is a common chronic neurological disease caused by the over-synchronization of neurons leading to brain dysfunction. Recurrent seizures can lead to cognitive and behavioral deficits, and irreversible brain damage. While the PI3K/Akt/mTOR pathway regulates various physiological processes of neurons and glia, it may also lead to abnormal neuronal signal transduction under pathological conditions, including that of epilepsy. Everolimus (Eve), an mTOR inhibitor, may modulate neuronal excitability and therefore exert protection against epilepsy. Therefore, this study aimed to investigate the neuroprotective effect of Everolimus on seizure-induced brain injury and its regulation of the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway. Kainic acid (KA) 15 mg/kg was used to induce seizures and Everolimus (1, 2, 5 mg/kg) was administered as a pretreatment. Hippocampal tissue was extracted 24 h post-seizure.
Results: The protein and mRNA expression levels of PI3K、p-AKt、p-mTOR、NF-kB and IL-6 as well as neuronal apoptosis and microglia activation, significantly increased after KA-induced seizures, however, these effects were inhibited by Everolimus treatment. Furthermore, pretreatment with Everolimus decreased seizure scores and increased seizure latency.
Conclusions: Everolimus can decrease the PI3K/Akt/mTOR and NF-kB/IL-6 signaling pathway, reduce neuronal apoptosis and microglia activation, and attenuate seizure susceptibility and intensity, thus having a protective effect on seizure-induced brain damage.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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