{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T09:15:25Z","timestamp":1769937325043,"version":"3.49.0"},"reference-count":68,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T00:00:00Z","timestamp":1670025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Type 1 spinocerebellar ataxia (SCA1) is a progressive neurodegenerative disorder with no effective treatment to date. Using mice modeling SCA1, it has been demonstrated that a drug that amplifies mGlu1 receptor activation (mGlu1 receptor PAM, Ro0711401) improves motor coordination without the development of tolerance when cerebellar dysfunction manifests (i.e., in 30-week-old heterozygous ataxin-1 [154Q\/2Q] transgenic mice). SCA1 is also associated with cognitive dysfunction, which may precede cerebellar motor signs. Here, we report that otherwise healthy, 8-week-old SCA1 mice showed a defect in spatial learning and memory associated with reduced protein levels of mGlu1\u03b1 receptors, the GluN2B subunit of NMDA receptors, and cannabinoid CB1 receptors in the hippocampus. Systemic treatment with Ro0711401 (10 mg\/kg, s.c.) partially corrected the learning deficit in the Morris water maze and restored memory retention in the SCA1 mice model. This treatment also enhanced hippocampal levels of the endocannabinoid, anandamide, without changing the levels of 2-arachidonylglycerol. These findings suggest that mGlu1 receptor PAMs may be beneficial in the treatment of motor and nonmotor signs associated with SCA1 and encourage further studies in animal models of SCA1 and other types of SCAs.<\/jats:p>","DOI":"10.3390\/cells11233916","type":"journal-article","created":{"date-parts":[[2022,12,5]],"date-time":"2022-12-05T04:40:09Z","timestamp":1670215209000},"page":"3916","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting mGlu1 Receptors in the Treatment of Motor and Cognitive Dysfunctions in Mice Modeling Type 1 Spinocerebellar Ataxia"],"prefix":"10.3390","volume":"11","author":[{"given":"Francesca","family":"Liberatore","sequence":"first","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nico","family":"Antenucci","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"},{"name":"Department of Pharmacology and Neuroscience, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6704-9023","authenticated-orcid":false,"given":"Daniel","family":"Tortolani","sequence":"additional","affiliation":[{"name":"European Center for Brain Research (CERC)\/Santa Lucia Foundation IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"Mascio","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9235-5874","authenticated-orcid":false,"given":"Federico","family":"Fanti","sequence":"additional","affiliation":[{"name":"Faculty of Bioscience and Technology for Food Agriculture and Environment, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Sergi","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Battaglia","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria","family":"Bruno","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ferdinando","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"},{"name":"Department of Physiology and Pharmacology, Sapienza University, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3990-2963","authenticated-orcid":false,"given":"Mauro","family":"Maccarrone","sequence":"additional","affiliation":[{"name":"European Center for Brain Research (CERC)\/Santa Lucia Foundation IRCCS, 00143 Rome, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4374-9233","authenticated-orcid":false,"given":"Serena","family":"Notartomaso","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, 86077 Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wu, Q.-W., and Kapfhammer, J.P. 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