title: 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.
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.
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yong-Zhi
authors.initials: YZ
authors.lastname: San
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Ping-Ping
authors.initials: PP
authors.lastname: Shi
authors.affiliation: Department of Neurology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Zhu
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000032:analysis; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D010433:Pentylenetetrazole / Q000633:toxicity; D000077205:Pioglitazone; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D045162:Thiazolidinediones / Q000494:pharmacology
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D010433:Pentylenetetrazole; D000077205:Pioglitazone