{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T13:26:12Z","timestamp":1790774772779,"version":"4.1.0"},"reference-count":78,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,9,15]],"date-time":"2016-09-15T00:00:00Z","timestamp":1473897600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003478","name":"Ministry of Health, Labour and Welfare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003478","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease caused by a gene defect, leading to movement disorder such as cerebellar ataxia.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>It remains largely unknown which functional defect contributes to the cerebellar ataxic phenotype in SCA1.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>\n                            In this study, we report progressive dysfunction of metabotropic glutamate receptor (mGluR) signalling, which leads to smaller slow synaptic responses, reduced dendritic Ca\n                            <jats:sup>2+<\/jats:sup>\n                            signals and impaired synaptic plasticity at cerebellar synapses, in the early disease stage of SCA1 model mice.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>We also show that enhancement of mGluR signalling by a clinically available drug, baclofen, leads to improvement of motor performance in SCA1 mice.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>SCA1 is an incurable disease with no effective treatment, and our results may provide mechanistic grounds for targeting mGluRs and a novel drug therapy with baclofen to treat SCA1 patients in the future.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Spinocerebellar ataxia type 1 (SCA1) is a progressive neurodegenerative disease that presents with cerebellar ataxia and motor learning defects. Previous studies have indicated that the pathology of SCA1, as well as other ataxic diseases, is related to signalling pathways mediated by the metabotropic glutamate receptor type 1 (mGluR1), which is indispensable for proper motor coordination and learning. However, the functional contribution of mGluR signalling to SCA1 pathology is unclear. In the present study, we show that SCA1 model mice develop a functional impairment of mGluR signalling which mediates slow synaptic responses, dendritic Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signals, and short\u2010 and long\u2010term synaptic plasticity at parallel fibre (PF)\u2013Purkinje cell (PC) synapses in a progressive manner from the early disease stage (5 postnatal weeks) prior to PC death. Notably, impairment of mGluR\u2010mediated dendritic Ca\n                      <jats:sup>2+<\/jats:sup>\n                      signals linearly correlated with a reduction of PC capacitance (cell surface area) in disease progression. Enhancement of mGluR signalling by baclofen, a clinically available GABA\n                      <jats:sub>B<\/jats:sub>\n                      receptor agonist, led to an improvement of motor performance in SCA1 mice and the improvement lasted \u223c1 week after a single application of baclofen. Moreover, the restoration of motor performance in baclofen\u2010treated SCA1 mice matched the functional recovery of mGluR\u2010mediated slow synaptic currents and mGluR\u2010dependent short\u2010 and long\u2010term synaptic plasticity. These results suggest that impairment of synaptic mGluR cascades is one of the important contributing factors to cerebellar ataxia in early and middle stages of SCA1 pathology, and that modulation of mGluR signalling by baclofen or other clinical interventions may be therapeutic targets to treat SCA1.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1113\/jp272950","type":"journal-article","created":{"date-parts":[[2016,7,21]],"date-time":"2016-07-21T03:22:52Z","timestamp":1469071372000},"page":"141-164","source":"Crossref","is-referenced-by-count":78,"title":["Progressive impairment of cerebellar mGluR signalling and its therapeutic potential for cerebellar ataxia in spinocerebellar ataxia type 1 model mice"],"prefix":"10.1113","volume":"595","author":[{"given":"Anton N.","family":"Shuvaev","sequence":"first","affiliation":[{"name":"Department of Neurophysiology and Neural Repair Gunma University Graduate School of Medicine  Maebashi Gunma 371\u20108511 Japan"},{"name":"Research Institute of Molecular Medicine and Pathobiochemistry Krasnoyarsk State Medical University named after Prof. V. F. Voino\u2010Yasenetsky  Krasnoyarsk 660022 Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobutake","family":"Hosoi","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neural Repair Gunma University Graduate School of Medicine  Maebashi Gunma 371\u20108511 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yamato","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Graduate School of Arts and Sciences University of Tokyo  Tokyo 153\u20108902 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dai","family":"Yanagihara","sequence":"additional","affiliation":[{"name":"Department of Life Sciences Graduate School of Arts and Sciences University of Tokyo  Tokyo 153\u20108902 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirokazu","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Neurophysiology and Neural Repair Gunma University Graduate School of Medicine  Maebashi Gunma 371\u20108511 Japan"},{"name":"Research Program for Neural Signalling Division of Endocrinology, Metabolism and Signal Research Gunma University Initiative for Advanced Research  Maebashi Gunma 371\u20108511 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,9,15]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90205-4"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0876-14.2014"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2579-11.2011"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-08-03469.2003"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-014-0564-5"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2014.756"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-010-0393-y"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-013-1550-7"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1752-0509-6-70"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1529\/biophysj.108.130195"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90273-2"},{"key":"e_1_2_6_13_1","doi-asserted-by":"crossref","first-page":"7664","DOI":"10.1523\/JNEUROSCI.21-19-07664.2001","article-title":"Endogenous activation of group\u2010I metabotropic glutamate receptors is required for differentiation and survival of cerebellar Purkinje cells","volume":"21","author":"Catania MV","year":"2001","journal-title":"J Neurosci"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3909-08.2008"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.17-19-07385.1997"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.10451"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/372237a0"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3011"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1357-15.2015"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/373155a0"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0813341106"},{"issue":"5","key":"e_1_2_6_22_1","first-page":"9","article-title":"The chemistry and kinetics of Lioresal","volume":"48","author":"Faigle JW","year":"1972","journal-title":"Postgrad Med J"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1124\/pr.108.000166"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3125"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/25541"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-011-0314-x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26096"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(10)58002-5"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1212673"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3312"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2005.11.080"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.019"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.009"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a006726"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2005.01.014"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0905-11.2011"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.85.4.1750"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neunet.2010.02.004"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-010-0195-4"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5567-12.2013"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2007.141010"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(01)80047-7"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.2270"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12311-013-0516-5"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/72101"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0660-09.2009"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2012.00182"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.207563"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-6-48"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2011.08.056"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2012.04.003"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2008.09.025"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2009.10.009"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1080\/14734220600791477"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00013.x"},{"key":"e_1_2_6_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2010.02.005"},{"key":"e_1_2_6_57_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddh268"},{"key":"e_1_2_6_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.09.036"},{"key":"e_1_2_6_59_1","doi-asserted-by":"publisher","DOI":"10.1248\/yakushi.13-00233"},{"key":"e_1_2_6_60_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.137.3530.610"},{"key":"e_1_2_6_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/40153"},{"key":"e_1_2_6_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)61766-X"},{"key":"e_1_2_6_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2611"},{"key":"e_1_2_6_64_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0405387101"},{"key":"e_1_2_6_65_1","doi-asserted-by":"publisher","DOI":"10.1080\/14734220600788911"},{"key":"e_1_2_6_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.07.058"},{"key":"e_1_2_6_67_1","doi-asserted-by":"publisher","DOI":"10.1038\/25547"},{"key":"e_1_2_6_68_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2001.86.3.1389"},{"key":"e_1_2_6_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06841.x"},{"key":"e_1_2_6_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2006.01.104"},{"key":"e_1_2_6_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/81792"},{"key":"e_1_2_6_72_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040182"},{"key":"e_1_2_6_73_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00733-X"},{"key":"e_1_2_6_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2009.03.011"},{"key":"e_1_2_6_75_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1076"},{"key":"e_1_2_6_76_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2014.00012"},{"key":"e_1_2_6_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-3940(99)00852-6"},{"key":"e_1_2_6_78_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02536"},{"key":"e_1_2_6_79_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2978-04.2004"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP272950","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2FJP272950","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/JP272950","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T20:04:09Z","timestamp":1696190649000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/JP272950"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,9,15]]},"references-count":78,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,1]]}},"alternative-id":["10.1113\/JP272950"],"URL":"https:\/\/doi.org\/10.1113\/jp272950","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.726569394.793529548","asserted-by":"object"}]},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,9,15]]}}}