title: Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice.
abstract: Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery is highly associated with POCD. Phosphodiesterase-4 (PDE4) is an enzyme that specifically hydrolyses cyclic adenosine monophosphate (cAMP), which plays an important role during neuroinflammation and the process of learning and memory. However, the role of PDE4 in the development of POCD remains unclear. Male 14-month-old C57BL/6 mice received carotid artery exposure to mimic POCD. First, we evaluated cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were investigated. Then, we used rolipram, a PDE4 inhibitor, to block the effects of PDE4. The cognitive performance of the mice and the expression of PDE4 subtypes, pro-inflammatory cytokines, p-CREB and PSD95 as well as cAMP levels were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, elevation of pro-inflammatory cytokines, and reduction in the expression of p-CREB, PSD95 and cAMP levels after surgery. The expression of PDE4B and PDE4D in the hippocampus decreased following blocking of PDE4 by rolipram. Meanwhile, rolipram attenuated the cognitive impairment and the elevation of pro-inflammatory cytokines induced by surgery. Moreover, rolipram reversed the reduction of p-CREB and PSD95. These results indicate that PDE4 subtype overexpression may be involved in the development of surgery-induced cognitive dysfunction in mice.
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China; Department of Anesthesiology, The General Hospital of the PLA Rocket Force, Beijing 100088, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Zhang
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Ze-Guo
authors.initials: ZG
authors.lastname: Feng
authors.affiliation: Departments of Anesthesiology and Critical Care Medicine, Peking University First Hospital, Beijing, 100034, China.
authors.forename: Dong-Xin
authors.initials: DX
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, The General Hospital of the PLA Rocket Force, Beijing 100088, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, The General Hospital of the PLA Rocket Force, Beijing 100088, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sui
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yong-Yi
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Wei-Xing
authors.initials: WX
authors.lastname: Zhao
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: dr_fuqiang@hotmail.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: xuzhipeng20@163.com.
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.affiliation: Anesthesia and Operation Center, Chinese PLA General Hospital, Beijing 100853, China. Electronic address: wwdd1962@aliyun.com.
authors.forename: Wei-Dong
authors.initials: WD
authors.lastname: Mi
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004660:Encephalitis / Q000150:complications / Q000378:metabolism*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009473:Neuronal Plasticity; D011183:Postoperative Complications / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; C543000:PDE4B protein, mouse; C531980:PDE4D protein, mouse
keywords: Cognitive impairment; Neuroinflammation; Phosphodiesterase-4; Postoperative cognitive dysfunction; Rolipram