Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain
Acute administration of MK-801 (dizocilpine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, can establish animal models of psychiatric disorders. However, the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain unknown. Here, we found rapid...
Gespeichert in:
| Veröffentlicht in: | Dōngwùxué yánjiū 2023-05, Vol.44 (3), p.543-555 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 555 |
|---|---|
| container_issue | 3 |
| container_start_page | 543 |
| container_title | Dōngwùxué yánjiū |
| container_volume | 44 |
| creator | Ni, Rong-Jun Wang, Yi-Yan Gao, Tian-Hao Wang, Qi-Run Wei, Jin-Xue Zhao, Lian-Sheng Ma, Yang-Rui Ma, Xiao-Hong Li, Tao |
| description | Acute administration of MK-801 (dizocilpine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, can establish animal models of psychiatric disorders. However, the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain unknown. Here, we found rapid elimination of microglia in the prefrontal cortex (PFC) and hippocampus (HPC) of mice following administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor PLX3397 (pexidartinib) in drinking water. Single administration of MK-801 induced hyperactivity in the open-field test (OFT). Importantly, PLX3397-induced depletion of microglia prevented the hyperactivity and schizophrenia-like behaviors induced by MK-801. However, neither repopulation of microglia nor inhibition of microglial activation by minocycline affected MK-801-induced hyperactivity. Importantly, microglial density in the PFC and HPC was significantly correlated with behavioral changes. In addition, common and distinct glutamate-, GABA-, and inflammation-related gene (116 genes) expression patterns were observed in the brains of PLX3397- and/or MK-801-treated mice. Moreover, 10 common inflammation-related genes (
,
,
,
,
,
,
,
,
, and
) with very strong correlations were identified in the brain using hierarchical clustering analysis. Further correlation analysis demonstrated that the behavioral changes in the OFT were most significantly associated with the expression of inflammation-related genes (
,
,
,
,
, and
), but not glutamate- or GABA-related genes in PLX3397- and MK-801-treated mice. Thus, our results suggest that microglial depletion via a CSF1R/c-Kit kinase inhibitor can ameliorate the hyperactivity induced by an NMDAR antagonist, which is associated with modulation of immune-related genes in the brain. |
| doi_str_mv | 10.24272/j.issn.2095-8137.2022.389 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_journals_2844842953</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2810917189</sourcerecordid><originalsourceid>FETCH-LOGICAL-c385t-c0d54b7ef47fa0a849d8903d4991cbccd2822c82936c772a64004877149c9d063</originalsourceid><addsrcrecordid>eNpdkctu1DAUhrMAtVXpKyALNmwy-JbYZoNQy01MVRYgsbMc28l4lNiD7RTNS_DMODNlVFj5yP7Of3z0VdULBFeYYoZfb1cuJb_CUDQ1R4SVCuMV4eJJdXG6PK-uUnIdbEoNMWrPqnPCEGUC8ovq943djTa74EHoweR0DMPoFPjl8gZ8Xf8gRDCgcrZ-VtkmcPul5hDVzptZWwM2-52NSmd37_IeqJSCdoUzx_5oh3lU2fkBON-PaprUMqmOdjxAg_Ul0nmQNxZ0UTn_rHraqzHZq4fzsvr-4f2360_1-u7j5-t361oT3uRaQ9PQjtmesl5BxakwXEBiqBBId1obzDHWHAvSasawaimElLOytdDCwJZcVm-Pubu5m6zR1ueoRrmLblJxL4Ny8t8X7zZyCPcSQUxaAkVJePWQEMPP2aYsJ5e0HUflbZiTxBxBgRjiC_ryP3Qb5ujLfoWilFMsGlKoN0eqKEgp2v70GwTlQbfcykW3XMzKxaxcdEtyGPH88T6n1r-iyR8AD6wN</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2844842953</pqid></control><display><type>article</type><title>Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><creator>Ni, Rong-Jun ; Wang, Yi-Yan ; Gao, Tian-Hao ; Wang, Qi-Run ; Wei, Jin-Xue ; Zhao, Lian-Sheng ; Ma, Yang-Rui ; Ma, Xiao-Hong ; Li, Tao</creator><creatorcontrib>Ni, Rong-Jun ; Wang, Yi-Yan ; Gao, Tian-Hao ; Wang, Qi-Run ; Wei, Jin-Xue ; Zhao, Lian-Sheng ; Ma, Yang-Rui ; Ma, Xiao-Hong ; Li, Tao ; 粤港澳大湾区脑科学与类脑研究中心, 广东 广州 510799, 中国 ; Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China ; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310014, China ; Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong 510799, China ; 金苹果锦城第一中学, 四川 成都, 中国 ; 浙江大学医学院附属精神卫生中心, 杭州市第七人民医院, 浙江 杭州310013, 中国 ; 浙江大学脑科学与脑医学学院NHC和CAMS医学神经生物学重点实验室, 教育部脑与脑机融合前沿科学中心, 浙江 杭州 310014, 中国 ; 四川省精神心理疾病临床医学研究中心, 四川 成都 610044, 中国 ; Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China ; 四川大学华西医院精神卫生中心和精神医学研究室, 四川 成都 610041, 中国 ; Golden Apple Jincheng NO.1 Secondary School, Chengdu, Sichuan 610213, China ; Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, Sichuan 610044, China</creatorcontrib><description>Acute administration of MK-801 (dizocilpine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, can establish animal models of psychiatric disorders. However, the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain unknown. Here, we found rapid elimination of microglia in the prefrontal cortex (PFC) and hippocampus (HPC) of mice following administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor PLX3397 (pexidartinib) in drinking water. Single administration of MK-801 induced hyperactivity in the open-field test (OFT). Importantly, PLX3397-induced depletion of microglia prevented the hyperactivity and schizophrenia-like behaviors induced by MK-801. However, neither repopulation of microglia nor inhibition of microglial activation by minocycline affected MK-801-induced hyperactivity. Importantly, microglial density in the PFC and HPC was significantly correlated with behavioral changes. In addition, common and distinct glutamate-, GABA-, and inflammation-related gene (116 genes) expression patterns were observed in the brains of PLX3397- and/or MK-801-treated mice. Moreover, 10 common inflammation-related genes (
,
,
,
,
,
,
,
,
, and
) with very strong correlations were identified in the brain using hierarchical clustering analysis. Further correlation analysis demonstrated that the behavioral changes in the OFT were most significantly associated with the expression of inflammation-related genes (
,
,
,
,
, and
), but not glutamate- or GABA-related genes in PLX3397- and MK-801-treated mice. Thus, our results suggest that microglial depletion via a CSF1R/c-Kit kinase inhibitor can ameliorate the hyperactivity induced by an NMDAR antagonist, which is associated with modulation of immune-related genes in the brain.</description><identifier>ISSN: 2095-8137</identifier><identifier>ISSN: 0254-5853</identifier><identifier>DOI: 10.24272/j.issn.2095-8137.2022.389</identifier><identifier>PMID: 37147908</identifier><language>eng</language><publisher>China: Kunming Institute of Zoology, The Chinese Academy of Sciences</publisher><subject>Animal models ; Animals ; Behavior ; Brain ; Brain - metabolism ; c-Kit protein ; CD11b antigen ; CD163 antigen ; Cluster analysis ; Clustering ; Colonies ; Colony-stimulating factor ; Correlation analysis ; CX3CR1 protein ; Depletion ; Disorders ; Dizocilpine ; Dizocilpine Maleate - metabolism ; Dizocilpine Maleate - pharmacology ; Drinking water ; Enzyme inhibitors ; Field tests ; gamma-Aminobutyric Acid - metabolism ; Gene expression ; Genes ; Genetic engineering ; Glutamate receptors ; Hyperactivity ; Inflammation ; Inflammation - chemically induced ; Inflammation - drug therapy ; Inflammation - genetics ; Inflammation - veterinary ; Inhibitors ; Kinases ; Macrophage colony-stimulating factor ; Membrane Glycoproteins - metabolism ; Mental disorders ; Mice ; Microglia ; Microglia - metabolism ; Minocycline ; N-Methyl-D-aspartic acid receptors ; Open-field behavior ; Prefrontal cortex ; Receptors ; Receptors, Immunologic - metabolism ; Repopulation ; Schizophrenia ; γ-Aminobutyric acid</subject><ispartof>Dōngwùxué yánjiū, 2023-05, Vol.44 (3), p.543-555</ispartof><rights>Copyright Kunming Institute of Zoology, The Chinese Academy of Sciences May 2023</rights><rights>2023 Editorial Office of Zoological Research, Kunming Institute of Zoology, Chinese Academy of Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-c0d54b7ef47fa0a849d8903d4991cbccd2822c82936c772a64004877149c9d063</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,777,781,882,27905,27906</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37147908$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ni, Rong-Jun</creatorcontrib><creatorcontrib>Wang, Yi-Yan</creatorcontrib><creatorcontrib>Gao, Tian-Hao</creatorcontrib><creatorcontrib>Wang, Qi-Run</creatorcontrib><creatorcontrib>Wei, Jin-Xue</creatorcontrib><creatorcontrib>Zhao, Lian-Sheng</creatorcontrib><creatorcontrib>Ma, Yang-Rui</creatorcontrib><creatorcontrib>Ma, Xiao-Hong</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>粤港澳大湾区脑科学与类脑研究中心, 广东 广州 510799, 中国</creatorcontrib><creatorcontrib>Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China</creatorcontrib><creatorcontrib>NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310014, China</creatorcontrib><creatorcontrib>Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong 510799, China</creatorcontrib><creatorcontrib>金苹果锦城第一中学, 四川 成都, 中国</creatorcontrib><creatorcontrib>浙江大学医学院附属精神卫生中心, 杭州市第七人民医院, 浙江 杭州310013, 中国</creatorcontrib><creatorcontrib>浙江大学脑科学与脑医学学院NHC和CAMS医学神经生物学重点实验室, 教育部脑与脑机融合前沿科学中心, 浙江 杭州 310014, 中国</creatorcontrib><creatorcontrib>四川省精神心理疾病临床医学研究中心, 四川 成都 610044, 中国</creatorcontrib><creatorcontrib>Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China</creatorcontrib><creatorcontrib>四川大学华西医院精神卫生中心和精神医学研究室, 四川 成都 610041, 中国</creatorcontrib><creatorcontrib>Golden Apple Jincheng NO.1 Secondary School, Chengdu, Sichuan 610213, China</creatorcontrib><creatorcontrib>Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, Sichuan 610044, China</creatorcontrib><title>Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain</title><title>Dōngwùxué yánjiū</title><addtitle>Zool Res</addtitle><description>Acute administration of MK-801 (dizocilpine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, can establish animal models of psychiatric disorders. However, the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain unknown. Here, we found rapid elimination of microglia in the prefrontal cortex (PFC) and hippocampus (HPC) of mice following administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor PLX3397 (pexidartinib) in drinking water. Single administration of MK-801 induced hyperactivity in the open-field test (OFT). Importantly, PLX3397-induced depletion of microglia prevented the hyperactivity and schizophrenia-like behaviors induced by MK-801. However, neither repopulation of microglia nor inhibition of microglial activation by minocycline affected MK-801-induced hyperactivity. Importantly, microglial density in the PFC and HPC was significantly correlated with behavioral changes. In addition, common and distinct glutamate-, GABA-, and inflammation-related gene (116 genes) expression patterns were observed in the brains of PLX3397- and/or MK-801-treated mice. Moreover, 10 common inflammation-related genes (
,
,
,
,
,
,
,
,
, and
) with very strong correlations were identified in the brain using hierarchical clustering analysis. Further correlation analysis demonstrated that the behavioral changes in the OFT were most significantly associated with the expression of inflammation-related genes (
,
,
,
,
, and
), but not glutamate- or GABA-related genes in PLX3397- and MK-801-treated mice. Thus, our results suggest that microglial depletion via a CSF1R/c-Kit kinase inhibitor can ameliorate the hyperactivity induced by an NMDAR antagonist, which is associated with modulation of immune-related genes in the brain.</description><subject>Animal models</subject><subject>Animals</subject><subject>Behavior</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>c-Kit protein</subject><subject>CD11b antigen</subject><subject>CD163 antigen</subject><subject>Cluster analysis</subject><subject>Clustering</subject><subject>Colonies</subject><subject>Colony-stimulating factor</subject><subject>Correlation analysis</subject><subject>CX3CR1 protein</subject><subject>Depletion</subject><subject>Disorders</subject><subject>Dizocilpine</subject><subject>Dizocilpine Maleate - metabolism</subject><subject>Dizocilpine Maleate - pharmacology</subject><subject>Drinking water</subject><subject>Enzyme inhibitors</subject><subject>Field tests</subject><subject>gamma-Aminobutyric Acid - metabolism</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic engineering</subject><subject>Glutamate receptors</subject><subject>Hyperactivity</subject><subject>Inflammation</subject><subject>Inflammation - chemically induced</subject><subject>Inflammation - drug therapy</subject><subject>Inflammation - genetics</subject><subject>Inflammation - veterinary</subject><subject>Inhibitors</subject><subject>Kinases</subject><subject>Macrophage colony-stimulating factor</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>Microglia</subject><subject>Microglia - metabolism</subject><subject>Minocycline</subject><subject>N-Methyl-D-aspartic acid receptors</subject><subject>Open-field behavior</subject><subject>Prefrontal cortex</subject><subject>Receptors</subject><subject>Receptors, Immunologic - metabolism</subject><subject>Repopulation</subject><subject>Schizophrenia</subject><subject>γ-Aminobutyric acid</subject><issn>2095-8137</issn><issn>0254-5853</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkctu1DAUhrMAtVXpKyALNmwy-JbYZoNQy01MVRYgsbMc28l4lNiD7RTNS_DMODNlVFj5yP7Of3z0VdULBFeYYoZfb1cuJb_CUDQ1R4SVCuMV4eJJdXG6PK-uUnIdbEoNMWrPqnPCEGUC8ovq943djTa74EHoweR0DMPoFPjl8gZ8Xf8gRDCgcrZ-VtkmcPul5hDVzptZWwM2-52NSmd37_IeqJSCdoUzx_5oh3lU2fkBON-PaprUMqmOdjxAg_Ul0nmQNxZ0UTn_rHraqzHZq4fzsvr-4f2360_1-u7j5-t361oT3uRaQ9PQjtmesl5BxakwXEBiqBBId1obzDHWHAvSasawaimElLOytdDCwJZcVm-Pubu5m6zR1ueoRrmLblJxL4Ny8t8X7zZyCPcSQUxaAkVJePWQEMPP2aYsJ5e0HUflbZiTxBxBgRjiC_ryP3Qb5ujLfoWilFMsGlKoN0eqKEgp2v70GwTlQbfcykW3XMzKxaxcdEtyGPH88T6n1r-iyR8AD6wN</recordid><startdate>20230518</startdate><enddate>20230518</enddate><creator>Ni, Rong-Jun</creator><creator>Wang, Yi-Yan</creator><creator>Gao, Tian-Hao</creator><creator>Wang, Qi-Run</creator><creator>Wei, Jin-Xue</creator><creator>Zhao, Lian-Sheng</creator><creator>Ma, Yang-Rui</creator><creator>Ma, Xiao-Hong</creator><creator>Li, Tao</creator><general>Kunming Institute of Zoology, The Chinese Academy of Sciences</general><general>Science Press</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BVBZV</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H95</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230518</creationdate><title>Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain</title><author>Ni, Rong-Jun ; Wang, Yi-Yan ; Gao, Tian-Hao ; Wang, Qi-Run ; Wei, Jin-Xue ; Zhao, Lian-Sheng ; Ma, Yang-Rui ; Ma, Xiao-Hong ; Li, Tao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c385t-c0d54b7ef47fa0a849d8903d4991cbccd2822c82936c772a64004877149c9d063</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Behavior</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>c-Kit protein</topic><topic>CD11b antigen</topic><topic>CD163 antigen</topic><topic>Cluster analysis</topic><topic>Clustering</topic><topic>Colonies</topic><topic>Colony-stimulating factor</topic><topic>Correlation analysis</topic><topic>CX3CR1 protein</topic><topic>Depletion</topic><topic>Disorders</topic><topic>Dizocilpine</topic><topic>Dizocilpine Maleate - metabolism</topic><topic>Dizocilpine Maleate - pharmacology</topic><topic>Drinking water</topic><topic>Enzyme inhibitors</topic><topic>Field tests</topic><topic>gamma-Aminobutyric Acid - metabolism</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Genetic engineering</topic><topic>Glutamate receptors</topic><topic>Hyperactivity</topic><topic>Inflammation</topic><topic>Inflammation - chemically induced</topic><topic>Inflammation - drug therapy</topic><topic>Inflammation - genetics</topic><topic>Inflammation - veterinary</topic><topic>Inhibitors</topic><topic>Kinases</topic><topic>Macrophage colony-stimulating factor</topic><topic>Membrane Glycoproteins - metabolism</topic><topic>Mental disorders</topic><topic>Mice</topic><topic>Microglia</topic><topic>Microglia - metabolism</topic><topic>Minocycline</topic><topic>N-Methyl-D-aspartic acid receptors</topic><topic>Open-field behavior</topic><topic>Prefrontal cortex</topic><topic>Receptors</topic><topic>Receptors, Immunologic - metabolism</topic><topic>Repopulation</topic><topic>Schizophrenia</topic><topic>γ-Aminobutyric acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ni, Rong-Jun</creatorcontrib><creatorcontrib>Wang, Yi-Yan</creatorcontrib><creatorcontrib>Gao, Tian-Hao</creatorcontrib><creatorcontrib>Wang, Qi-Run</creatorcontrib><creatorcontrib>Wei, Jin-Xue</creatorcontrib><creatorcontrib>Zhao, Lian-Sheng</creatorcontrib><creatorcontrib>Ma, Yang-Rui</creatorcontrib><creatorcontrib>Ma, Xiao-Hong</creatorcontrib><creatorcontrib>Li, Tao</creatorcontrib><creatorcontrib>粤港澳大湾区脑科学与类脑研究中心, 广东 广州 510799, 中国</creatorcontrib><creatorcontrib>Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China</creatorcontrib><creatorcontrib>NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310014, China</creatorcontrib><creatorcontrib>Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong 510799, China</creatorcontrib><creatorcontrib>金苹果锦城第一中学, 四川 成都, 中国</creatorcontrib><creatorcontrib>浙江大学医学院附属精神卫生中心, 杭州市第七人民医院, 浙江 杭州310013, 中国</creatorcontrib><creatorcontrib>浙江大学脑科学与脑医学学院NHC和CAMS医学神经生物学重点实验室, 教育部脑与脑机融合前沿科学中心, 浙江 杭州 310014, 中国</creatorcontrib><creatorcontrib>四川省精神心理疾病临床医学研究中心, 四川 成都 610044, 中国</creatorcontrib><creatorcontrib>Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China</creatorcontrib><creatorcontrib>四川大学华西医院精神卫生中心和精神医学研究室, 四川 成都 610041, 中国</creatorcontrib><creatorcontrib>Golden Apple Jincheng NO.1 Secondary School, Chengdu, Sichuan 610213, China</creatorcontrib><creatorcontrib>Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, Sichuan 610044, China</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>East & South Asia Database</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Dōngwùxué yánjiū</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ni, Rong-Jun</au><au>Wang, Yi-Yan</au><au>Gao, Tian-Hao</au><au>Wang, Qi-Run</au><au>Wei, Jin-Xue</au><au>Zhao, Lian-Sheng</au><au>Ma, Yang-Rui</au><au>Ma, Xiao-Hong</au><au>Li, Tao</au><aucorp>粤港澳大湾区脑科学与类脑研究中心, 广东 广州 510799, 中国</aucorp><aucorp>Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China</aucorp><aucorp>NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science and Brain-machine Integration, School of Brain Science and Brain Medicine, Zhejiang University, Hangzhou, Zhejiang 310014, China</aucorp><aucorp>Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, Guangdong 510799, China</aucorp><aucorp>金苹果锦城第一中学, 四川 成都, 中国</aucorp><aucorp>浙江大学医学院附属精神卫生中心, 杭州市第七人民医院, 浙江 杭州310013, 中国</aucorp><aucorp>浙江大学脑科学与脑医学学院NHC和CAMS医学神经生物学重点实验室, 教育部脑与脑机融合前沿科学中心, 浙江 杭州 310014, 中国</aucorp><aucorp>四川省精神心理疾病临床医学研究中心, 四川 成都 610044, 中国</aucorp><aucorp>Mental Health Center and Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China</aucorp><aucorp>四川大学华西医院精神卫生中心和精神医学研究室, 四川 成都 610041, 中国</aucorp><aucorp>Golden Apple Jincheng NO.1 Secondary School, Chengdu, Sichuan 610213, China</aucorp><aucorp>Sichuan Clinical Medical Research Center for Mental Disorders, Chengdu, Sichuan 610044, China</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain</atitle><jtitle>Dōngwùxué yánjiū</jtitle><addtitle>Zool Res</addtitle><date>2023-05-18</date><risdate>2023</risdate><volume>44</volume><issue>3</issue><spage>543</spage><epage>555</epage><pages>543-555</pages><issn>2095-8137</issn><issn>0254-5853</issn><abstract>Acute administration of MK-801 (dizocilpine), an N-methyl-D-aspartate receptor (NMDAR) antagonist, can establish animal models of psychiatric disorders. However, the roles of microglia and inflammation-related genes in these animal models of psychiatric disorders remain unknown. Here, we found rapid elimination of microglia in the prefrontal cortex (PFC) and hippocampus (HPC) of mice following administration of the dual colony-stimulating factor 1 receptor (CSF1R)/c-Kit kinase inhibitor PLX3397 (pexidartinib) in drinking water. Single administration of MK-801 induced hyperactivity in the open-field test (OFT). Importantly, PLX3397-induced depletion of microglia prevented the hyperactivity and schizophrenia-like behaviors induced by MK-801. However, neither repopulation of microglia nor inhibition of microglial activation by minocycline affected MK-801-induced hyperactivity. Importantly, microglial density in the PFC and HPC was significantly correlated with behavioral changes. In addition, common and distinct glutamate-, GABA-, and inflammation-related gene (116 genes) expression patterns were observed in the brains of PLX3397- and/or MK-801-treated mice. Moreover, 10 common inflammation-related genes (
,
,
,
,
,
,
,
,
, and
) with very strong correlations were identified in the brain using hierarchical clustering analysis. Further correlation analysis demonstrated that the behavioral changes in the OFT were most significantly associated with the expression of inflammation-related genes (
,
,
,
,
, and
), but not glutamate- or GABA-related genes in PLX3397- and MK-801-treated mice. Thus, our results suggest that microglial depletion via a CSF1R/c-Kit kinase inhibitor can ameliorate the hyperactivity induced by an NMDAR antagonist, which is associated with modulation of immune-related genes in the brain.</abstract><cop>China</cop><pub>Kunming Institute of Zoology, The Chinese Academy of Sciences</pub><pmid>37147908</pmid><doi>10.24272/j.issn.2095-8137.2022.389</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2095-8137 |
| ispartof | Dōngwùxué yánjiū, 2023-05, Vol.44 (3), p.543-555 |
| issn | 2095-8137 0254-5853 |
| language | eng |
| recordid | cdi_proquest_journals_2844842953 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animal models Animals Behavior Brain Brain - metabolism c-Kit protein CD11b antigen CD163 antigen Cluster analysis Clustering Colonies Colony-stimulating factor Correlation analysis CX3CR1 protein Depletion Disorders Dizocilpine Dizocilpine Maleate - metabolism Dizocilpine Maleate - pharmacology Drinking water Enzyme inhibitors Field tests gamma-Aminobutyric Acid - metabolism Gene expression Genes Genetic engineering Glutamate receptors Hyperactivity Inflammation Inflammation - chemically induced Inflammation - drug therapy Inflammation - genetics Inflammation - veterinary Inhibitors Kinases Macrophage colony-stimulating factor Membrane Glycoproteins - metabolism Mental disorders Mice Microglia Microglia - metabolism Minocycline N-Methyl-D-aspartic acid receptors Open-field behavior Prefrontal cortex Receptors Receptors, Immunologic - metabolism Repopulation Schizophrenia γ-Aminobutyric acid |
| title | Depletion of microglia with PLX3397 attenuates MK-801-induced hyperactivity associated with regulating inflammation-related genes in the brain |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-18T08%3A10%3A59IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Depletion%20of%20microglia%20with%20PLX3397%20attenuates%20MK-801-induced%20hyperactivity%20associated%20with%20regulating%20inflammation-related%20genes%20in%20the%20brain&rft.jtitle=D%C5%8Dngw%C3%B9xu%C3%A9%20y%C3%A1nji%C5%AB&rft.au=Ni,%20Rong-Jun&rft.aucorp=%E7%B2%A4%E6%B8%AF%E6%BE%B3%E5%A4%A7%E6%B9%BE%E5%8C%BA%E8%84%91%E7%A7%91%E5%AD%A6%E4%B8%8E%E7%B1%BB%E8%84%91%E7%A0%94%E7%A9%B6%E4%B8%AD%E5%BF%83,%20%E5%B9%BF%E4%B8%9C%20%E5%B9%BF%E5%B7%9E%20510799,%20%E4%B8%AD%E5%9B%BD&rft.date=2023-05-18&rft.volume=44&rft.issue=3&rft.spage=543&rft.epage=555&rft.pages=543-555&rft.issn=2095-8137&rft_id=info:doi/10.24272/j.issn.2095-8137.2022.389&rft_dat=%3Cproquest_pubme%3E2810917189%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2844842953&rft_id=info:pmid/37147908&rfr_iscdi=true |