Peroxisome proliferatoractivated receptorγ agonist inhibits the mammalian target of rapamycin signaling pathway and has a protective effect in a rat model of status epilepticus
Peroxisome proliferatoractivated receptor γ (PPARγ) has a protective role in several neurological diseases. The present study investigated the effect of the PPARγ 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 PTZinduced SE was examined to determine the timepoint of peak activity, as reflected by phopshorylated (p)mTOR/mTOR and pS6/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 IL6 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 pmTOR/mTOR and pS6/S6 ratios peaked on the third day. Compared with the vehicle treatedSE group, pretreatment with pioglitazone was associated with the loss of fewer neurons, lower levels of IL1β and IL6, and inhibition of the activation of the mTOR signaling pathway. Therefore, the mTOR signaling pathway was activated in the PTZinduced SE rat model, and the PPARγ agonist, pioglitazone, had a neuroprotective effect, by inhibiting activation of the mTOR pathway and preventing the increase in the levels of IL1β and IL6.
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Document Type: Research Article
Affiliations: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China
Publication date: August 1, 2015
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