Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 43, Issue -, Pages 53-61Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.intimp.2016.12.003
Keywords
Postoperative cognitive decline; PPAR gamma; Aged; Neuroinflammation
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Funding
- National Natural Science Foundation of China [81400876]
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Neuroinflammation plays a key role in many neurodegenerative disorders, including postoperative cognitive decline (POCD). Growing evidence has demonstrated that activation of the peroxisome proliferator-activated receptor-gamma (PPAR gamma) attenuates the inflammatory response and improves cognitive dysfunction associated with many neuropsychiatric disorders. We hypothesize that down-regulation of PPAR gamma is linked to neuroinflammation and the subsequent cognitive deficits observed in an animal model of POCD. In the present study, the POCD animal model was established by performing an exploratory laparotomy under isoflurane anesthesia in 20-month-old male C57BL/6 mice. Behavioral tests, inflammatory biomarkers, including tumor necrosis factor-alpha(TNF-alpha), interleukin-6 (IL-6), interleukin-1 beta, ionized calcium-binding adaptor molecule-1 (IBA1)-positive cells, as well as glial fibrillary acidic protein (GFAP)-positive cells and brain-derived neurotrophic factor (BDNF), were measured. Herein, we showed that surgery induced profound impairment in cognition that was associated with significant decreases in PPAR gamma and BDNF expression, and significant increases in IL-1 beta, IBA1-positive cells, and GFAP-positive cells in the hippocampus. As expected, the PPAR gamma agonist pioglitazone attenuated the surgery-induced inflammatory changes and rescued the associated cognitive impairment. However, these beneficial effects were abolished by the PPAR gamma specific antagonist GW9662, suggesting a pivotal role of the PPAR gamma pathway in the pathogenesis of POCD. Taken together, our results provide evidence that down regulation of PPAR gamma may be involved in neuroinflammation and subsequent POCD, and suggest that activation of PPAR gamma by pioglitazone may represent a new way to prevent or treat POCD. (C) 2016 Elsevier B.V. All rights reserved.
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