{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T15:02:29Z","timestamp":1788966149668,"version":"build-2803163510"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Streptozotocin-induced diabetic rats (STZ rats), an established animal model of type 1 diabetes mellitus, develop cognitive decline, which has been linked to impairments in hippocampal synaptic plasticity. Long-term depression (LTD) in the hippocampus may be induced by the activation of different types of G protein-coupled receptors, particularly metabotropic glutamate receptors (mGluRs) and muscarinic acetylcholine receptors. We previously demonstrated that acetylcholine receptor activation-dependent LTD was impaired in STZ rats, and herein investigated group I mGluR (mGluR1\/5)-dependent LTD in the Schaffer collateral-CA1 synapses of STZ rats. Extracellular field recordings revealed that the chemical activation of mGluR1\/5 with (S)-3,5-dihydroxyphenylglycine (DHPG, 50\u202f\u03bcM, 10\u202fmin) induced sustained LTD in both control and STZ rats; however, the magnitude of DHPG-LTD was significantly smaller in STZ rats. Moreover, the paired-pulse ratio between before and 80\u202fmin after the application of DHPG increased in both control and STZ rats, and DHPG-LTD was independent of NMDA receptor activation. A Western blot analysis showed that DHPG-induced extracellular signal-regulated kinase (ERK) phosphorylation was reduced in STZ rats, whereas DHPG-induced phosphoinositide-dependent kinase 1 phosphorylation and the expression level of the scaffold protein, Homer1, were unchanged. Collectively, these results suggest that impaired ERK\/MAPK signaling affected hippocampal mGluR1\/5-dependent LTD in STZ rats, and the dysregulation of ERK may contribute to diabetes-associated cognitive decline because of its crucial role in protein synthesis-dependent synaptic plasticity.<\/jats:p>","DOI":"10.3389\/fnins.2026.1814915","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T05:42:58Z","timestamp":1775022178000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Attenuation of mGluR1\/5-dependent synaptic plasticity and ERK pathway dysfunction in the hippocampus of diabetic rats"],"prefix":"10.3389","volume":"20","author":[{"given":"Hayuma","family":"Otsuka","sequence":"first","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science","place":["Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sachie","family":"Sasaki-Hamada","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science","place":["Chiba, Japan"]},{"name":"Department of Physiology, School of Allied Health Sciences, Kitasato University","place":["Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Ishibashi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Allied Health Sciences, Kitasato University","place":["Kanagawa, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ichiro","family":"Oka","sequence":"additional","affiliation":[{"name":"Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences, Tokyo University of Science","place":["Chiba, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2996","DOI":"10.1128\/MCB.00201-08","article-title":"mGluR-dependent long-term depression is associated with increased phosphorylation of S6 and synthesis of elongation factor 1A but remains expressed in S6K-deficient mice","volume":"28","author":"Antion","year":"2008","journal-title":"Mol. 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