title: Differential Effects of Pioglitazone in the Hippocampal CA1 Region Following Transient Forebrain Ischemia in Low- and High-Fat Diet-Fed Gerbils.
abstract: In the present study, we investigated the effects of pioglitazone (PGZ) in the hippocampal CA1 region of low- or high-fat diet (LFD or HFD) fed gerbils after transient forebrain ischemia. After 8 weeks of LFD or HFD feeding, PGZ (30 mg/kg) was intraperitoneally administered to the gerbils, following which ischemia was induced by occlusion of the bilateral common carotid arteries for 5 min. Administration of PGZ significantly reduced the ischemia-induced hyperactivity 1 day after ischemia/reperfusion in both LFD- and HFD-fed gerbils. At 4 days after ischemia/reperfusion, the neurons were significantly reduced and microglial activation was observed in the hippocampal CA1 region in LFD- and HFD-fed gerbils. The microglial activation was more prominent in the HFD-fed gerbils compared to the LFD-fed gerbils. Administration of PGZ ameliorated ischemia-induced neuronal death and microglial activation in the hippocampal CA1 region 4 days after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-gerbils. At 6 h after ischemia/reperfusion, tumor necrosis factor-α (TNF-α) and interlukin-1β (IL-1β) levels were significantly increased in the hippocampal homogenates of LFD-fed group compared to control group, and HFD feeding further increased TNF-α and IL-1β levels. PGZ treatment significantly ameliorated the increase of TNF-α and IL-1β levels in LFD-fed gerbils, not in the HFD-fed gerbils. At 12 h after ischemia/reperfusion, superoxide dismutase (SOD) and malondialdehyde (MDA) levels in hippocampal homogenates were significantly increased in the LFD-fed group compared to the control group, and HFD feeding significantly showed relatively reduction in SOD activity and increase in MDA level. PGZ administration significantly reduced the increase in MDA levels 12 h after ischemia/reperfusion in the LFD-fed gerbils, but not in the HFD-fed gerbils. These results suggest that PGZ ameliorates the neuronal damage induced by ischemia by maintaining the TNF-α, IL-1β, SOD and MDA levels in LFD-fed gerbils. In addition, HFD feeding affects the modulation of these parameters in the hippocampus after transient forebrain ischemia.
authors.affiliation: Department of Neurosurgery, Dongtan Sacred Heart Hospital, College of Medicine, Hallym University, Hwaseong, 445-907, South Korea, nsmsm@chol.com.
authors.forename: Seung Myung
authors.initials: SM
authors.lastname: Moon
authors.forename: Goang-Min
authors.initials: GM
authors.lastname: Choi
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Yoo
authors.forename: Hyo Young
authors.initials: HY
authors.lastname: Jung
authors.forename: Hee Sun
authors.initials: HS
authors.lastname: Yim
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: In Koo
authors.initials: IK
authors.lastname: Hwang
authors.forename: Byung Moon
authors.initials: BM
authors.lastname: Cho
authors.forename: In Bok
authors.initials: IB
authors.lastname: Chang
authors.forename: Sung-Min
authors.initials: SM
authors.lastname: Cho
authors.forename: Moo-Ho
authors.initials: MH
authors.lastname: Won
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018752:Diet, Fat-Restricted / Q000639:trends; D059305:Diet, High-Fat / Q000009:adverse effects* / Q000639:trends; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D000077205:Pioglitazone; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045162:Thiazolidinediones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone