The effects of PPAR-γ agonist pioglitazone on hippocampal cytokines, brain-derived neurotrophic factor, memory impairment, and oxidative stress status in lipopolysaccharide-treated rats

Document Type : Original Article


1 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Basic Science and Neuroscience Research Center, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

3 Iranshahr University of Medical Sciences, Iranshahr, Iran

4 Department of Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran


Objective(s): The aim of current study was to evaluate improving effects of pioglitazone as an agonist of peroxisome proliferator-activated receptor gamma (PPARγ), on brain-derived neurotrophic factor (BDNF) and cytokines as well as tissue oxidative damage criteria in the hippocampus in a rat model of lipopolysaccharide (LPS) induced memory impairment.
Materials and Methods: The rats were classified and treated as follows (10 rats per group): (1) vehicle, (2) vehicle before LPS (1 mg/kg, 120 min before memory tests), (3-5) pioglitazone 10, 20 or 30 mg/kg 30 min before LPS. Finally, the hippocampal tissues were collected for biomedical analyses.
Results: In the Morris water maze test, the LPS group, had a longer latency to find the platform while they spent a shorter time in the target quadrant in the probe trial. In the passive avoidance test, the animals of the LPS group had shorter delay times to enter the dark compartment than those of the control group. Treatment with 20 and 30 mg of pioglitazone corrected these parameters. In the hippocampus of LPS group interleukin-6, tumor necrosis factor-α, nitric oxide metabolites, and malondialdehyde were higher while  thiol, BDNF, and IL-10 concentrations and the activities of catalase (CAT) and superoxide dismutase (SOD) were lower than the control group. Treatment by both doses of 20 and 30 mg of pioglitazone corrected the biochemical parameters in the hippocampus.
Conclusion: The current findings revealed that pioglitazone protected the rats from learning and memory impairment induced by LPS. The effects were associated with improvement of cytokines, oxidative stress criteria, and BDNF.


Main Subjects

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