Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice
•Surgery induced overexpression of PDE4B and PDE4D in mice.•Surgery induced accumulation of pro-inflammatory cytokines and cognitive impairment.•Inhibition of PDE4 attenuated the cognitive impairment.•Inhibition of PDE4 attenuated the accumulation of pro-inflammatory cytokines. Postoperative cogniti...
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| Veröffentlicht in: | Brain research bulletin 2017-04, Vol.130, p.274-282 |
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| creator | Wang, Wei Zhang, Xiao-ying Feng, Ze-guo Wang, Dong-xin Zhang, Hao Sui, Bo Zhang, Yong-yi Zhao, Wei-xing Fu, Qiang Xu, Zhi-peng Mi, Wei-dong |
| description | •Surgery induced overexpression of PDE4B and PDE4D in mice.•Surgery induced accumulation of pro-inflammatory cytokines and cognitive impairment.•Inhibition of PDE4 attenuated the cognitive impairment.•Inhibition of PDE4 attenuated the accumulation of pro-inflammatory cytokines.
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. |
| doi_str_mv | 10.1016/j.brainresbull.2017.02.006 |
| format | Article |
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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.</description><identifier>ISSN: 0361-9230</identifier><identifier>EISSN: 1873-2747</identifier><identifier>DOI: 10.1016/j.brainresbull.2017.02.006</identifier><identifier>PMID: 28235598</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Behavior, Animal ; Cognitive Dysfunction - etiology ; Cognitive Dysfunction - metabolism ; Cognitive impairment ; Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism ; Cytokines - metabolism ; Encephalitis - complications ; Encephalitis - metabolism ; Inflammation Mediators - metabolism ; Male ; Mice, Inbred C57BL ; Motor Activity ; Neuroinflammation ; Neuronal Plasticity ; Phosphodiesterase-4 ; Postoperative cognitive dysfunction ; Postoperative Complications - metabolism ; Rolipram</subject><ispartof>Brain research bulletin, 2017-04, Vol.130, p.274-282</ispartof><rights>2017 Elsevier Inc.</rights><rights>Copyright © 2017 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c380t-a387145f7e6dea91584e0a4e28fdb3618c94a120e8a6a28f053690a0411535273</citedby><cites>FETCH-LOGICAL-c380t-a387145f7e6dea91584e0a4e28fdb3618c94a120e8a6a28f053690a0411535273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S036192301630226X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28235598$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Zhang, Xiao-ying</creatorcontrib><creatorcontrib>Feng, Ze-guo</creatorcontrib><creatorcontrib>Wang, Dong-xin</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Sui, Bo</creatorcontrib><creatorcontrib>Zhang, Yong-yi</creatorcontrib><creatorcontrib>Zhao, Wei-xing</creatorcontrib><creatorcontrib>Fu, Qiang</creatorcontrib><creatorcontrib>Xu, Zhi-peng</creatorcontrib><creatorcontrib>Mi, Wei-dong</creatorcontrib><title>Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice</title><title>Brain research bulletin</title><addtitle>Brain Res Bull</addtitle><description>•Surgery induced overexpression of PDE4B and PDE4D in mice.•Surgery induced accumulation of pro-inflammatory cytokines and cognitive impairment.•Inhibition of PDE4 attenuated the cognitive impairment.•Inhibition of PDE4 attenuated the accumulation of pro-inflammatory cytokines.
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.</description><subject>Animals</subject><subject>Behavior, Animal</subject><subject>Cognitive Dysfunction - etiology</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Cognitive impairment</subject><subject>Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Encephalitis - complications</subject><subject>Encephalitis - metabolism</subject><subject>Inflammation Mediators - metabolism</subject><subject>Male</subject><subject>Mice, Inbred C57BL</subject><subject>Motor Activity</subject><subject>Neuroinflammation</subject><subject>Neuronal Plasticity</subject><subject>Phosphodiesterase-4</subject><subject>Postoperative cognitive dysfunction</subject><subject>Postoperative Complications - metabolism</subject><subject>Rolipram</subject><issn>0361-9230</issn><issn>1873-2747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkM1u1DAUhS1ERYeWV0ARKzYJ_okThx1qoSBV6qZdW459UzxK7GAnUWfDs3OHKYglC8vW8Tn36nyEvGO0YpQ1H_ZVn4wPCXK_jmPFKWsryitKmxdkx1QrSt7W7Uuyo6JhZccFPSevc95TdCjZvCLnXHEhZad25OfdBgmeZhyWfQxFHIr5e8x4nIe8QDIZyrrIa78cZsiFD1scN3D4QDE9QjqUPrjVohRgTdGHYTTTZJbjNBNcYeNj8IvfoHCHPKzB_v7B-OQtXJKzwYwZ3jzfF-Thy-f7q6_l7d3Nt6tPt6UVii6lEapltRxaaByYjklVAzU1cDW4Hksq29WGcQrKNAZFKkXTUUNrxqSQvBUX5P1p7pzijxWL6clnC-NoAsQ1a6TGZdtILtD68WS1KeacYNBz8pNJB82oPvLXe_0vf33krynXSBfDb5_3rP0E7m_0D3A0XJ8MgG03D0ln6yEgPp_ALtpF_z97fgEsnKEZ</recordid><startdate>201704</startdate><enddate>201704</enddate><creator>Wang, Wei</creator><creator>Zhang, Xiao-ying</creator><creator>Feng, Ze-guo</creator><creator>Wang, Dong-xin</creator><creator>Zhang, Hao</creator><creator>Sui, Bo</creator><creator>Zhang, Yong-yi</creator><creator>Zhao, Wei-xing</creator><creator>Fu, Qiang</creator><creator>Xu, Zhi-peng</creator><creator>Mi, Wei-dong</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>201704</creationdate><title>Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice</title><author>Wang, Wei ; Zhang, Xiao-ying ; Feng, Ze-guo ; Wang, Dong-xin ; Zhang, Hao ; Sui, Bo ; Zhang, Yong-yi ; Zhao, Wei-xing ; Fu, Qiang ; Xu, Zhi-peng ; Mi, Wei-dong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c380t-a387145f7e6dea91584e0a4e28fdb3618c94a120e8a6a28f053690a0411535273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Animals</topic><topic>Behavior, Animal</topic><topic>Cognitive Dysfunction - etiology</topic><topic>Cognitive Dysfunction - metabolism</topic><topic>Cognitive impairment</topic><topic>Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Encephalitis - complications</topic><topic>Encephalitis - metabolism</topic><topic>Inflammation Mediators - metabolism</topic><topic>Male</topic><topic>Mice, Inbred C57BL</topic><topic>Motor Activity</topic><topic>Neuroinflammation</topic><topic>Neuronal Plasticity</topic><topic>Phosphodiesterase-4</topic><topic>Postoperative cognitive dysfunction</topic><topic>Postoperative Complications - metabolism</topic><topic>Rolipram</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Wei</creatorcontrib><creatorcontrib>Zhang, Xiao-ying</creatorcontrib><creatorcontrib>Feng, Ze-guo</creatorcontrib><creatorcontrib>Wang, Dong-xin</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Sui, Bo</creatorcontrib><creatorcontrib>Zhang, Yong-yi</creatorcontrib><creatorcontrib>Zhao, Wei-xing</creatorcontrib><creatorcontrib>Fu, Qiang</creatorcontrib><creatorcontrib>Xu, Zhi-peng</creatorcontrib><creatorcontrib>Mi, Wei-dong</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Brain research bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Wei</au><au>Zhang, Xiao-ying</au><au>Feng, Ze-guo</au><au>Wang, Dong-xin</au><au>Zhang, Hao</au><au>Sui, Bo</au><au>Zhang, Yong-yi</au><au>Zhao, Wei-xing</au><au>Fu, Qiang</au><au>Xu, Zhi-peng</au><au>Mi, Wei-dong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice</atitle><jtitle>Brain research bulletin</jtitle><addtitle>Brain Res Bull</addtitle><date>2017-04</date><risdate>2017</risdate><volume>130</volume><spage>274</spage><epage>282</epage><pages>274-282</pages><issn>0361-9230</issn><eissn>1873-2747</eissn><abstract>•Surgery induced overexpression of PDE4B and PDE4D in mice.•Surgery induced accumulation of pro-inflammatory cytokines and cognitive impairment.•Inhibition of PDE4 attenuated the cognitive impairment.•Inhibition of PDE4 attenuated the accumulation of pro-inflammatory cytokines.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>28235598</pmid><doi>10.1016/j.brainresbull.2017.02.006</doi><tpages>9</tpages></addata></record> |
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| subjects | Animals Behavior, Animal Cognitive Dysfunction - etiology Cognitive Dysfunction - metabolism Cognitive impairment Cyclic Nucleotide Phosphodiesterases, Type 4 - metabolism Cytokines - metabolism Encephalitis - complications Encephalitis - metabolism Inflammation Mediators - metabolism Male Mice, Inbred C57BL Motor Activity Neuroinflammation Neuronal Plasticity Phosphodiesterase-4 Postoperative cognitive dysfunction Postoperative Complications - metabolism Rolipram |
| title | Overexpression of phosphodiesterase-4 subtypes involved in surgery-induced neuroinflammation and cognitive dysfunction in mice |
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