{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,2]],"date-time":"2025-08-02T14:41:29Z","timestamp":1754145689452,"version":"3.41.2"},"reference-count":72,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,6,12]],"date-time":"2025-06-12T00:00:00Z","timestamp":1749686400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32200950"],"award-info":[{"award-number":["32200950"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515011106"],"award-info":[{"award-number":["2022A1515011106"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic stress causes variable profiles of physiological deficits, including mood disorders, sleep disorders, and memory deficits. However, the neural mechanisms and potential drug targets of chronic stress\u2010induced memory deficit remain elusive.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>This study aimed to explore the function and regulatory mechanisms of metabotropic glutamate receptor 5 (mGluR5) in chronic stress\u2010induced memory deficit and investigate the potential therapeutic target for stress\u2010related memory deficit.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Behavioral tests were used to assess the effects of chronic stress on memory. Electrophysiological recordings were conducted to examine the synaptic inputs after chronic stress. RNA sequencing was employed to achieve transcriptional alterations in the hippocampus after stress or mGluR5 knockdown. Enrichment analysis was performed to identify the downstream effector of chronic stress\u2010induced memory deficits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chronic restraint stress (CRS) impairs hippocampal\u2010dependent memory and electrophysiological recordings reveal that chronic stress impairs synaptic inputs. Subsequently, we observe that the mGluR5 level declines after CRS, which is an important molecule for learning and memory. mGluR5 knockdown induces memory deficits and impairs synaptic inputs. Enhancement of mGluR5 activity by CDPPB could restore chronic stress\u2010induced memory deficits and rescue impaired synaptic inputs. Furthermore, we identify that pituitary adenylyl cyclase activating peptide (PACAP) is down\u2010regulated after CRS and mGluR5 knockdown. PACAP application could restore the impaired inhibitory synaptic inputs after CRS.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results illuminate that the mGluR5 mediates chronic stress\u2010induced memory deficits, which may provide promising strategies for treating stress\u2010related memory deficits.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70477","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T02:15:02Z","timestamp":1749780902000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["mGluR5 in Pyramidal Neurons in the Hippocampus Mediates Chronic Stress\u2010Induced Memory Deficits"],"prefix":"10.1111","volume":"31","author":[{"given":"Hong\u2010Cheng","family":"Lu","sequence":"first","affiliation":[{"name":"Pingshan District Peoples' Hospital of Shenzhen  Shenzhen Guangdong People's Republic of China"},{"name":"Pingshan Hospital Southern Medical University  Shenzhen Guangdong People's Republic of China"},{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Center for Brain Science and Brain\u2010Inspired Intelligence, Guangdong\u2010Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences Southern Medical University  Guangzhou..."},{"name":"State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhuo\u2010Jun","family":"Du","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Center for Brain Science and Brain\u2010Inspired Intelligence, Guangdong\u2010Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences Southern Medical University  Guangzhou..."},{"name":"State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Center for Brain Science and Brain\u2010Inspired Intelligence, Guangdong\u2010Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences Southern Medical University  Guangzhou..."},{"name":"State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Guo","sequence":"additional","affiliation":[{"name":"Key Laboratory of Mental Health of the Ministry of Education, Guangdong\u2010Hong Kong\u2010Macao Greater Bay Area Center for Brain Science and Brain\u2010Inspired Intelligence, Guangdong\u2010Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Province Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences Southern Medical University  Guangzhou..."},{"name":"State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shu\u2010Cai","family":"Yang","sequence":"additional","affiliation":[{"name":"Pingshan District Peoples' Hospital of Shenzhen  Shenzhen Guangdong People's Republic of China"},{"name":"Pingshan Hospital Southern Medical University  Shenzhen Guangdong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-0198","authenticated-orcid":false,"given":"Xin","family":"Li","sequence":"additional","affiliation":[{"name":"Pingshan District Peoples' Hospital of Shenzhen  Shenzhen Guangdong People's Republic of China"},{"name":"Pingshan Hospital Southern Medical University  Shenzhen Guangdong People's Republic of China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,12]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-018-0031-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.70187"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14486"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2009.04.013"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2009.09040461"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn849"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.02.020"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2016.155"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2023674118"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-024-00806-0"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2023.03.017"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0666-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.12.004"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.09.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264-022-00968-w"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-022-00599-0"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2009.11.003"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22604"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2016.11.017"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2018.02.005"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01548-w"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0076-6"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.07.017"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2184"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.14695"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108799"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2016.08.007"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.308"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.02.045"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhq093"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-05925.2001"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5716-08.2009"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.05.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2018.00318"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00524"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-018-0972-5"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2023.107792"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-010-9372-7"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.10.061"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.34200"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12181"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107752"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00594.2014"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2021.173273"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2014.08.002"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.079244"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14555"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/ejn.13285"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2012.10.010"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107785"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.031666.113"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2009.07.022"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aba7394"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2009.11.007"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.147"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-020-0652-9"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-018-0295-2"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2015.112"},{"key":"e_1_2_10_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2006.10.011"},{"key":"e_1_2_10_61_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708644104"},{"key":"e_1_2_10_62_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-13-05196.1997"},{"key":"e_1_2_10_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2018.03.007"},{"key":"e_1_2_10_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01441-y"},{"key":"e_1_2_10_65_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2224-18.2019"},{"key":"e_1_2_10_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2020.09.008"},{"key":"e_1_2_10_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2019.109682"},{"key":"e_1_2_10_68_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.08.010"},{"key":"e_1_2_10_69_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5474-05.2006"},{"key":"e_1_2_10_70_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1076-17.2017"},{"key":"e_1_2_10_71_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2007.01.031"},{"key":"e_1_2_10_72_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0567-18.2018"},{"key":"e_1_2_10_73_1","first-page":"1011","article-title":"Inconsistent Effects of Sleep Deprivation on Memory Function","volume":"20","author":"Vaseghi S.","year":"2021","journal-title":"EXCLI Journal"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.70477","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T08:29:16Z","timestamp":1752740956000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.70477"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6]]},"references-count":72,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1111\/cns.70477"],"URL":"https:\/\/doi.org\/10.1111\/cns.70477","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"type":"print","value":"1755-5930"},{"type":"electronic","value":"1755-5949"}],"subject":[],"published":{"date-parts":[[2025,6]]},"assertion":[{"value":"2025-02-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-03","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70477"}}