Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammatory cognitive dysfunction in mice

Publication date: Available online 21 February 2017
Source:Brain Research Bulletin
Author(s): Wei Wang, Qiang Fu, Xiao-ying Zhang, Ze-guo Feng, Hao Zhang, Bo Sui, Yong-yi Zhang, Wei-xing Zhao, Zhi-peng Xu, Wei-dong Mi
Postoperative cognitive dysfunction (POCD) is characterized by cognitive impairments in patients after surgery. Hippocampal neuroinflammation induced by surgery has been recognized as a pathogenesis of 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 the cognitive performance by a Morris water maze (MWM) and fear conditioning system (FCS) test after surgery. The expression of PDE4 subtypes, pro-inflammatory cytokines, cAMP, p-CREB and PSD95 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, cAMP, p-CREB and PSD95 were examined again. Mice displayed learning and memory impairment, overexpression of PDE4B and PDE4D, accumulation of pro-inflammatory cytokines, and reduction in the expression of cAMP, p-CREB and PSD95 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 accumulation 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.



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