{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T20:45:27Z","timestamp":1780778727470,"version":"3.54.1"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201322"],"award-info":[{"award-number":["82201322"]}],"id":[{"id":"10.13039\/501100001809","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":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aberrant metabotropic glutamate receptor 2\/3 (mGluR2\/3) signaling has been implicated in the synaptic and cognitive deficits observed in Alzheimer's disease (AD), yet the underlying regulatory mechanisms remain unclear. This study investigated the therapeutic potential of LY341495, a selective mGluR2\/3 antagonist, in APP\/PS1 transgenic mice, a widely used AD model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male APP\/PS1 mice were treated with the selective mGluR2\/3 antagonist LY341495. Cognitive performance was evaluated using behavioral tests. Hippocampal dentate gyrus (DG) alterations were examined by immunohistochemistry and electrophysiology, including analyses of mGluR2\/3 expression, excitatory synaptic activity, adult neurogenesis, calbindin expression, and amyloid\u2010\u03b2 plaque burden.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>APP\/PS1 mice exhibited pathological upregulation of mGluR2\/3 in the DG, accompanied by altered presynaptic glutamatergic transmission, reduced neurogenesis, decreased calbindin expression, and deficits in recognition and spatial memory. LY341495 treatment attenuated the aberrant mGluR2\/3 upregulation, enhanced excitatory synaptic activity, and improved calbindin levels and neurogenesis in the DG. Importantly, these changes were associated with significant reductions in DG amyloid\u2010\u03b2 plaque burden and marked improvements in cognitive performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study highlights the novelty of linking mGluR2\/3 inhibition to the restoration of calcium\u2010buffering capacity, as reflected by calbindin expression and neurogenesis, processes critical for DG plasticity and resilience. These findings underscore the therapeutic potential of LY341495 as a novel intervention targeting mGluR2\/3 signaling in AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70916","type":"journal-article","created":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T09:23:22Z","timestamp":1778837002000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Targeting\n                    <scp>mGluR2<\/scp>\n                    \/3 Signaling With\n                    <scp>LY341495<\/scp>\n                    Restores Dentate Gyrus Function and Cognitive Performance in a Male Mouse Model of Alzheimer's Disease"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0254-855X","authenticated-orcid":false,"given":"Cui\u2010Ping","family":"Chen","sequence":"first","affiliation":[{"name":"Cerebrovascular Disease Center, Ningbo Key Laboratory of Nervous System and Brain Function The 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