The Effects of PPAR-γ Agonist Pioglitazone on Hippocampal Cytokines, Brain-Derived Neurotrophic Factor, Memory Impairment, andOxidative Stress Status in Lipopolysaccharide- Treated Rats

In the present study, the effects of pioglitazone on hippocampal cytokines, brain-derived neurotrophic factor (BDNF), oxidative stress status and memory in lipopolysaccharide (LPS) treated rats were investigated. Materials and Methods: The rats were divided into five groups (n=10 in each) :(1) control, (2) LPS (1 mg/kg, two hours before behavioral tests), (3-5) LPS-Pio 10 mg, LPS-Pio 20 mg and LPS-Pio 30 mg groups (10, 20 or 30 mg/kg pio 30 min before LPS). Finally, we removed brain tissue for biochemical measurements. Results: In LPS group, the escapelatency in Morris water maze test was longer while, the delay timeto enter the dark compartment in passive avoidance test were significantly shorter than in the control. Treatment by 20 and 30 mg of pioglitazone corrected these parameters. Malondialdehyde (MDA), nitric oxide metabolites, interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) concentration in the hippocampus of LPS group were higher than controlgroup while, in LPS-Pio20mg an LPS-Pio30mg group they were lower than LPS group. The thiol content, IL- 10 concentration and the activities of catalase (CAT) and superoxide dismutase (SOD) in hippocampal tissues of LPS group reduced compared to control group. Thesefactors enhanced in LPS-Pio20 mg and LPS-Pio30 mg groups compared to LPS. The hippocampal content of BDNF in LPS group was significantly lower compared to the control group. All treated groups had higher BDNF content in comparison to LPS group. Conclusion: Thefindings indicated that protective effects of pioglitazone against LPS-induced memory impairment were accompanied by decreasing of inflammatory cytokines, oxidative stress and increasing of BDNF.