Peroxisome proliferator‑activated receptor‑γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus

San,Yong‑Zhi; Liu,Yu; Zhang,Yu; Shi,Ping‑Ping; Zhu,Yu‑Lan

doi:10.3892/mmr.2015.3641

Peroxisome proliferator‑activated receptor‑γ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus

Authors:
- Yong‑Zhi San
- Yu Liu
- Yu Zhang
- Ping‑Ping Shi
- Yu‑Lan Zhu
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Affiliations: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Published online on: April 17, 2015 https://doi.org/10.3892/mmr.2015.3641
Pages: 1877-1883
Copyright: © San et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Peroxisome proliferator‑activated receptor γ (PPAR‑γ) has a protective role in several neurological diseases. The present study investigated the effect of the PPAR‑γ agonist, pioglitazone, on the mammalian target of rapamycin (mTOR) signaling pathway in a rat model of pentylenetetrazol (PTZ)‑induced status epilepticus (SE). The investigation proceeded in two stages. First, the course of activation of the mTOR signaling pathway in PTZ‑induced SE was examined to determine the time‑point of peak activity, as reflected by phopshorylated (p)‑mTOR/mTOR and p‑S6/S6 ratios. Subsequently, pioglitazone was administrated intragastrically to investigate its effect on the mTOR signaling pathway, through western blot and immunochemical analyses. The levels of the interleukin (IL)‑1β and IL‑6 inflammatory cytokines were detected using ELISA, and neuronal loss was observed via Nissl staining. In the first stage of experimentation, the mTOR signaling pathway was activated, and the p‑mTOR/mTOR and p‑S6/S6 ratios peaked on the third day. Compared with the vehicle treated‑SE group, pretreatment with pioglitazone was associated with the loss of fewer neurons, lower levels of IL‑1β and IL‑6, and inhibition of the activation of the mTOR signaling pathway. Therefore, the mTOR signaling pathway was activated in the PTZ‑induced SE rat model, and the PPAR‑γ agonist, pioglitazone, had a neuroprotective effect, by inhibiting activation of the mTOR pathway and preventing the increase in the levels of IL‑1β and IL‑6.

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