Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse
Nowadays, there are few studies in vivo to explore the effects of Human Cytomegalovirus (HCMV) single gene such as immediate early protein 2 (IE2) on the nervous system, let alone the mechanism that IE2 causes cognitive impairment. In this study, the Rosa26-LSL-IE2/Cre mouse was used to show the eff...
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| Veröffentlicht in: | Behavioural brain research 2022-02, Vol.419, p.113683-113683, Article 113683 |
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| creator | Niu, Junyun Wang, Zhifei Liu, Lili Zhang, Xianjuan Niu, Delei Liu, Ting Qiao, Hongye Lu, Ran Nan, Fulong Tian, Zibin Wang, Bin |
| description | Nowadays, there are few studies in vivo to explore the effects of Human Cytomegalovirus (HCMV) single gene such as immediate early protein 2 (IE2) on the nervous system, let alone the mechanism that IE2 causes cognitive impairment. In this study, the Rosa26-LSL-IE2/Cre mouse was used to show the effects of IE2 on the cognitive ability and the GluNRs/CaMKIIα/CREB signaling pathway in the hippocampus. We divided the mice into experimental and control groups based on the results of PCR firstly. After that, the cognitive abilities of the two groups were compared through new object recognition (NOR) and Morris water maze (MWM) tests. The results of the behavioral tests showed that the cognitive ability of the experimental mice was lower than that of the control group. It is known that changes in the expression levels of N-methyl D-aspartate receptor 1, 2A, and 2B (GluN1, GluN2A, GluN2B) affect synaptic plasticity and cause cognitive changes. Finally, we analyzed the expression levels of GluN1, GluN2A, GluN2B, and related signaling pathway molecules by qPCR and western blot. We found that the expression levels of the GluNRs/CaMKIIα/CREB signaling pathway were decreased in the experimental group. These results indicated that IE2 could affect the expression levels of GluNRs/CaMKIIα/CREB signaling pathway, which was closely related to the cognitive impairment of the experimental group. In summary, we used this novel mouse model to show that IE2 could cause cognitive impairment in the hippocampus, which might be related to the GluNRs/CaMKIIα/CREB signaling pathway. It is helpful to further understand the mechanism of the cognitive impairment induced by HCMV IE2.
•Human cytomegalovirus IE2 could be stably expressed and inherited in the hippocampus of the Rosa26-LSL-IE2/Cre mice.•HCMV IE2 destroyed the structure of hippocampus in the Rosa26-LSL-IE2/Cre mouse.•HCMV IE2 caused cognitive impairment in the hippocampus.•The cognitive impairment caused by IE2 might through the GluNRs/CaMKIIα/CREB signaling pathway. |
| doi_str_mv | 10.1016/j.bbr.2021.113683 |
| format | Article |
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•Human cytomegalovirus IE2 could be stably expressed and inherited in the hippocampus of the Rosa26-LSL-IE2/Cre mice.•HCMV IE2 destroyed the structure of hippocampus in the Rosa26-LSL-IE2/Cre mouse.•HCMV IE2 caused cognitive impairment in the hippocampus.•The cognitive impairment caused by IE2 might through the GluNRs/CaMKIIα/CREB signaling pathway.</description><identifier>ISSN: 0166-4328</identifier><identifier>EISSN: 1872-7549</identifier><identifier>DOI: 10.1016/j.bbr.2021.113683</identifier><identifier>PMID: 34838933</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism ; Cognitive ability ; Cognitive Dysfunction - metabolism ; Cyclic AMP Response Element-Binding Protein - metabolism ; Cytomegalovirus - genetics ; Disease Models, Animal ; Hippocampus - metabolism ; Immediate early protein 2 (IE2) ; Immediate-Early Proteins - metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mouse model ; N-methyl D-aspartate receptor ; Receptors, N-Methyl-D-Aspartate - metabolism ; Signal Transduction - physiology ; Viral Proteins - metabolism</subject><ispartof>Behavioural brain research, 2022-02, Vol.419, p.113683-113683, Article 113683</ispartof><rights>2021 Elsevier B.V.</rights><rights>Copyright © 2021 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-a734b021d5f65e13f09ada59283a305e845a45dcfff7c453b67ad4154d0dc2d03</citedby><cites>FETCH-LOGICAL-c353t-a734b021d5f65e13f09ada59283a305e845a45dcfff7c453b67ad4154d0dc2d03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbr.2021.113683$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34838933$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Niu, Junyun</creatorcontrib><creatorcontrib>Wang, Zhifei</creatorcontrib><creatorcontrib>Liu, Lili</creatorcontrib><creatorcontrib>Zhang, Xianjuan</creatorcontrib><creatorcontrib>Niu, Delei</creatorcontrib><creatorcontrib>Liu, Ting</creatorcontrib><creatorcontrib>Qiao, Hongye</creatorcontrib><creatorcontrib>Lu, Ran</creatorcontrib><creatorcontrib>Nan, Fulong</creatorcontrib><creatorcontrib>Tian, Zibin</creatorcontrib><creatorcontrib>Wang, Bin</creatorcontrib><title>Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse</title><title>Behavioural brain research</title><addtitle>Behav Brain Res</addtitle><description>Nowadays, there are few studies in vivo to explore the effects of Human Cytomegalovirus (HCMV) single gene such as immediate early protein 2 (IE2) on the nervous system, let alone the mechanism that IE2 causes cognitive impairment. In this study, the Rosa26-LSL-IE2/Cre mouse was used to show the effects of IE2 on the cognitive ability and the GluNRs/CaMKIIα/CREB signaling pathway in the hippocampus. We divided the mice into experimental and control groups based on the results of PCR firstly. After that, the cognitive abilities of the two groups were compared through new object recognition (NOR) and Morris water maze (MWM) tests. The results of the behavioral tests showed that the cognitive ability of the experimental mice was lower than that of the control group. It is known that changes in the expression levels of N-methyl D-aspartate receptor 1, 2A, and 2B (GluN1, GluN2A, GluN2B) affect synaptic plasticity and cause cognitive changes. Finally, we analyzed the expression levels of GluN1, GluN2A, GluN2B, and related signaling pathway molecules by qPCR and western blot. We found that the expression levels of the GluNRs/CaMKIIα/CREB signaling pathway were decreased in the experimental group. These results indicated that IE2 could affect the expression levels of GluNRs/CaMKIIα/CREB signaling pathway, which was closely related to the cognitive impairment of the experimental group. In summary, we used this novel mouse model to show that IE2 could cause cognitive impairment in the hippocampus, which might be related to the GluNRs/CaMKIIα/CREB signaling pathway. It is helpful to further understand the mechanism of the cognitive impairment induced by HCMV IE2.
•Human cytomegalovirus IE2 could be stably expressed and inherited in the hippocampus of the Rosa26-LSL-IE2/Cre mice.•HCMV IE2 destroyed the structure of hippocampus in the Rosa26-LSL-IE2/Cre mouse.•HCMV IE2 caused cognitive impairment in the hippocampus.•The cognitive impairment caused by IE2 might through the GluNRs/CaMKIIα/CREB signaling pathway.</description><subject>Animals</subject><subject>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</subject><subject>Cognitive ability</subject><subject>Cognitive Dysfunction - metabolism</subject><subject>Cyclic AMP Response Element-Binding Protein - metabolism</subject><subject>Cytomegalovirus - genetics</subject><subject>Disease Models, Animal</subject><subject>Hippocampus - metabolism</subject><subject>Immediate early protein 2 (IE2)</subject><subject>Immediate-Early Proteins - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Transgenic</subject><subject>Mouse model</subject><subject>N-methyl D-aspartate receptor</subject><subject>Receptors, N-Methyl-D-Aspartate - metabolism</subject><subject>Signal Transduction - physiology</subject><subject>Viral Proteins - metabolism</subject><issn>0166-4328</issn><issn>1872-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO0zAQhi0EYsvCA3BBPnJJa8d2kooTRGW3ooBU4GxNbCdxlcTBTor6NrwCL8Iz4bYLR04jeb7_n_H8CL2kZEkJzVaHZVX5ZUpSuqSUZQV7hBa0yNMkF3z9GC0ikyWcpcUNehbCgRDCiaBP0Q3jBSvWjC3Qz_u5hwGr0-R600DnjtbPAW83Ke7hhG0_gvV4ag1WrhnsZI8GQ2U7O52wqy-N1o6jU9CPUTe13s1Ne3m_6-ZP-7Aq4eOH7fb3r1W537zDwTYDdHZo8AhT--M8YrjQexcgzZLdl10Sh69Kb3Dv5mCeoyc1dMG8eKi36Nv7zdfyPtl9vtuWb3eJYoJNCeSMV_EQWtSZMJTVZA0axDotGDAiTMEFcKFVXde54oJVWQ6aU8E10SrVhN2i11ff0bvvswmT7G1QputgMHEPmWaEcyHiBSNKr6jyLgRvajl624M_SUrkORh5kDEYeQ5GXoOJmlcP9nPVG_1P8TeJCLy5AiZ-8miNl0FZMyijrTdqktrZ_9j_ATj4nw0</recordid><startdate>20220215</startdate><enddate>20220215</enddate><creator>Niu, Junyun</creator><creator>Wang, Zhifei</creator><creator>Liu, Lili</creator><creator>Zhang, Xianjuan</creator><creator>Niu, Delei</creator><creator>Liu, Ting</creator><creator>Qiao, Hongye</creator><creator>Lu, Ran</creator><creator>Nan, Fulong</creator><creator>Tian, Zibin</creator><creator>Wang, Bin</creator><general>Elsevier B.V</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>20220215</creationdate><title>Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse</title><author>Niu, Junyun ; Wang, Zhifei ; Liu, Lili ; Zhang, Xianjuan ; Niu, Delei ; Liu, Ting ; Qiao, Hongye ; Lu, Ran ; Nan, Fulong ; Tian, Zibin ; Wang, Bin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-a734b021d5f65e13f09ada59283a305e845a45dcfff7c453b67ad4154d0dc2d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism</topic><topic>Cognitive ability</topic><topic>Cognitive Dysfunction - metabolism</topic><topic>Cyclic AMP Response Element-Binding Protein - metabolism</topic><topic>Cytomegalovirus - genetics</topic><topic>Disease Models, Animal</topic><topic>Hippocampus - metabolism</topic><topic>Immediate early protein 2 (IE2)</topic><topic>Immediate-Early Proteins - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Transgenic</topic><topic>Mouse model</topic><topic>N-methyl D-aspartate receptor</topic><topic>Receptors, N-Methyl-D-Aspartate - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Niu, Junyun</creatorcontrib><creatorcontrib>Wang, Zhifei</creatorcontrib><creatorcontrib>Liu, Lili</creatorcontrib><creatorcontrib>Zhang, Xianjuan</creatorcontrib><creatorcontrib>Niu, Delei</creatorcontrib><creatorcontrib>Liu, Ting</creatorcontrib><creatorcontrib>Qiao, Hongye</creatorcontrib><creatorcontrib>Lu, Ran</creatorcontrib><creatorcontrib>Nan, Fulong</creatorcontrib><creatorcontrib>Tian, Zibin</creatorcontrib><creatorcontrib>Wang, Bin</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>Behavioural brain research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Niu, Junyun</au><au>Wang, Zhifei</au><au>Liu, Lili</au><au>Zhang, Xianjuan</au><au>Niu, Delei</au><au>Liu, Ting</au><au>Qiao, Hongye</au><au>Lu, Ran</au><au>Nan, Fulong</au><au>Tian, Zibin</au><au>Wang, Bin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse</atitle><jtitle>Behavioural brain research</jtitle><addtitle>Behav Brain Res</addtitle><date>2022-02-15</date><risdate>2022</risdate><volume>419</volume><spage>113683</spage><epage>113683</epage><pages>113683-113683</pages><artnum>113683</artnum><issn>0166-4328</issn><eissn>1872-7549</eissn><abstract>Nowadays, there are few studies in vivo to explore the effects of Human Cytomegalovirus (HCMV) single gene such as immediate early protein 2 (IE2) on the nervous system, let alone the mechanism that IE2 causes cognitive impairment. In this study, the Rosa26-LSL-IE2/Cre mouse was used to show the effects of IE2 on the cognitive ability and the GluNRs/CaMKIIα/CREB signaling pathway in the hippocampus. We divided the mice into experimental and control groups based on the results of PCR firstly. After that, the cognitive abilities of the two groups were compared through new object recognition (NOR) and Morris water maze (MWM) tests. The results of the behavioral tests showed that the cognitive ability of the experimental mice was lower than that of the control group. It is known that changes in the expression levels of N-methyl D-aspartate receptor 1, 2A, and 2B (GluN1, GluN2A, GluN2B) affect synaptic plasticity and cause cognitive changes. Finally, we analyzed the expression levels of GluN1, GluN2A, GluN2B, and related signaling pathway molecules by qPCR and western blot. We found that the expression levels of the GluNRs/CaMKIIα/CREB signaling pathway were decreased in the experimental group. These results indicated that IE2 could affect the expression levels of GluNRs/CaMKIIα/CREB signaling pathway, which was closely related to the cognitive impairment of the experimental group. In summary, we used this novel mouse model to show that IE2 could cause cognitive impairment in the hippocampus, which might be related to the GluNRs/CaMKIIα/CREB signaling pathway. It is helpful to further understand the mechanism of the cognitive impairment induced by HCMV IE2.
•Human cytomegalovirus IE2 could be stably expressed and inherited in the hippocampus of the Rosa26-LSL-IE2/Cre mice.•HCMV IE2 destroyed the structure of hippocampus in the Rosa26-LSL-IE2/Cre mouse.•HCMV IE2 caused cognitive impairment in the hippocampus.•The cognitive impairment caused by IE2 might through the GluNRs/CaMKIIα/CREB signaling pathway.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>34838933</pmid><doi>10.1016/j.bbr.2021.113683</doi><tpages>1</tpages></addata></record> |
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| subjects | Animals Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism Cognitive ability Cognitive Dysfunction - metabolism Cyclic AMP Response Element-Binding Protein - metabolism Cytomegalovirus - genetics Disease Models, Animal Hippocampus - metabolism Immediate early protein 2 (IE2) Immediate-Early Proteins - metabolism Mice Mice, Inbred C57BL Mice, Transgenic Mouse model N-methyl D-aspartate receptor Receptors, N-Methyl-D-Aspartate - metabolism Signal Transduction - physiology Viral Proteins - metabolism |
| title | Human cytomegalovirus IE2 may impair the cognitive ability of the hippocampus through the GluNRs/CaMKIIα/CREB signaling pathway in the Rosa26-LSL-IE2/Cre mouse |
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