{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:14:09Z","timestamp":1787318049443,"version":"build-2736575974"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,4,10]],"date-time":"2018-04-10T00:00:00Z","timestamp":1523318400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"CIHR","doi-asserted-by":"crossref","award":["119437"],"award-info":[{"award-number":["119437"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Brain"],"published-print":{"date-parts":[[2018,12]]},"DOI":"10.1186\/s13041-018-0364-9","type":"journal-article","created":{"date-parts":[[2018,4,19]],"date-time":"2018-04-19T11:16:31Z","timestamp":1524136591000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Autophagy is increased following either pharmacological or genetic silencing of mGluR5 signaling in Alzheimer\u2019s disease mouse models"],"prefix":"10.1186","volume":"11","author":[{"given":"Khaled S.","family":"Abd-Elrahman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison","family":"Hamilton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Vasefi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0887-7312","authenticated-orcid":false,"given":"Stephen S. G.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2018,4,10]]},"reference":[{"key":"364_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.jalz.2016.03.001","volume":"12","author":"Alzheimer\u2019s Association","year":"2016","unstructured":"Alzheimer\u2019s Association. 2016 Alzheimer\u2019s disease facts and figures. Alzheimers Dement. 2016;12:459\u2013509. [cited 2017 Nov 16] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27570871","journal-title":"Alzheimers Dement"},{"key":"364_CR2","first-page":"208","volume":"35","author":"DA Casey","year":"2010","unstructured":"Casey DA, Antimisiaris D, O\u2019Brien J. Drugs for Alzheimer\u2019s disease: are they effective? P T. 2010;35:208\u201311. [cited 2017 Nov 16] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20498822 . MediMedia, USA","journal-title":"P T"},{"key":"364_CR3","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1177\/1756285609102724","volume":"2","author":"KL Lanct\u00f4t","year":"2009","unstructured":"Lanct\u00f4t KL, Rajaram RD, Herrmann N. Therapy for Alzheimer\u2019s disease: how effective are current treatments? Ther Adv Neurol Disord. 2009;2:163\u201380. [cited 2017 Nov 16] Available from: http:\/\/wwew.ncbi.nlm.nih.gov\/pubmed\/21179526 . SAGE Publications","journal-title":"Ther Adv Neurol Disord"},{"key":"#cr-split#-364_CR4.1","doi-asserted-by":"crossref","unstructured":"1. Hunter S, Brayne C. Understanding the roles of mutations in the amyloid precursor protein in Alzheimer disease. Mol Psychiatry. 2017","DOI":"10.1038\/mp.2017.218"},{"key":"#cr-split#-364_CR4.2","unstructured":"2. [cited 2017 Nov 16] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29112196"},{"key":"364_CR5","doi-asserted-by":"crossref","unstructured":"Kamenetz F, Tomita T, Hsieh H, Seabrook G, Borchelt D, Iwatsubo T, et al. APP processing and synaptic function. Neuron. 2003;37:925\u2013937. [cited 2017 Nov 16] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12670422 .","DOI":"10.1016\/S0896-6273(03)00124-7"},{"key":"364_CR6","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s13041-015-0107-0","volume":"8","author":"A Hamilton","year":"2015","unstructured":"Hamilton A, Zamponi GW, SSG F. Glutamate receptors function as scaffolds for the regulation of \u03b2-amyloid and cellular prion protein signaling complexes. Mol Brain. 2015;8:18. [cited 2017 Nov 15] Available from: http:\/\/www.molecularbrain.com\/content\/8\/1\/18","journal-title":"Mol Brain"},{"key":"364_CR7","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1523\/JNEUROSCI.4974-09.2010","volume":"30","author":"FM Ribeiro","year":"2010","unstructured":"Ribeiro FM, Paquet M, Ferreira LT, Cregan T, Swan P, Cregan SP, et al. Metabotropic glutamate receptor-mediated cell signaling pathways are altered in a mouse model of Huntington\u2019s disease. J Neurosci. 2010;30:316\u201324. [cited 2016 Oct 20] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/20053912","journal-title":"J Neurosci"},{"key":"364_CR8","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1016\/j.neuron.2013.06.036","volume":"79","author":"JW Um","year":"2013","unstructured":"Um JW, Kaufman AC, Kostylev M, Heiss JK, Stagi M, Takahashi H, et al. Metabotropic glutamate receptor 5 is a Coreceptor for Alzheimer A\u03b2 oligomer bound to cellular prion protein. Neuron. 2013;79:887\u2013902. [cited 2016 Nov 15] Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627313005527","journal-title":"Neuron"},{"key":"364_CR9","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.neuron.2010.04.029","volume":"66","author":"M Renner","year":"2010","unstructured":"Renner M, Lacor PN, Velasco PT, Xu J, Contractor A, Klein WL, et al. Deleterious effects of amyloid beta oligomers acting as an extracellular scaffold for mGluR5. Neuron. 2010;66:739\u201354. [cited 2017 Nov 15] Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0896627310003223","journal-title":"Neuron"},{"key":"364_CR10","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1212\/WNL.0b013e3182166dc7","volume":"76","author":"DK Sokol","year":"2011","unstructured":"Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology. 2011;76:1344\u201352. [cited 2017 Nov 15] Available from: http:\/\/www.neurology.org\/cgi\/doi\/10.1212\/WNL.0b013e3182166dc7","journal-title":"Neurology"},{"key":"364_CR11","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1756-6606-7-40","volume":"7","author":"A Hamilton","year":"2014","unstructured":"Hamilton A, Esseltine JL, DeVries RA, Cregan SP, SSG F. Metabotropic glutamate receptor 5 knockout reduces cognitive impairment and pathogenesis in a mouse model of Alzheimer\u2019s disease. Mol. Brain. 2014;7:40. [cited 2016 Oct 19] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24886239","journal-title":"Mol. Brain"},{"key":"364_CR12","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.1016\/j.celrep.2016.04.077","volume":"15","author":"A Hamilton","year":"2016","unstructured":"Hamilton A, Vasefi M, Vander Tuin C, RJ MQ, Anisman H, SSG F. Chronic pharmacological mGluR5 inhibition prevents cognitive impairment and reduces pathogenesis in an Alzheimer disease mouse model. Cell Rep. 2016;15:1859\u201365. [cited 2016 Oct 19] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/27210751","journal-title":"Cell Rep"},{"key":"364_CR13","doi-asserted-by":"publisher","first-page":"2030","DOI":"10.1093\/hmg\/ddt598","volume":"23","author":"FM Ribeiro","year":"2014","unstructured":"Ribeiro FM, Devries RA, Hamilton A, Guimaraes IM, Cregan SP, Pires RGW, et al. Metabotropic glutamate receptor 5 knockout promotes motor and biochemical alterations in a mouse model of Huntington\u2019s disease. Hum Mol Genet. 2014;23:2030\u201342. [cited 2016 Oct 19] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24282028","journal-title":"Hum Mol Genet"},{"key":"364_CR14","doi-asserted-by":"publisher","first-page":"eaan6387","DOI":"10.1126\/scisignal.aan6387","volume":"10","author":"KS Abd-Elrahman","year":"2017","unstructured":"Abd-Elrahman KS, Hamilton A, Hutchinson SR, Liu F, Russell RC, SSG F. mGluR5 antagonism increases autophagy and prevents disease progression in the zQ175 mouse model of Huntington\u2019s disease. Sci Signal. 2017;10:eaan6387. [cited 2018 Jan 30] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29259100","journal-title":"Sci Signal"},{"key":"364_CR15","doi-asserted-by":"publisher","first-page":"12297","DOI":"10.1074\/jbc.M900573200","volume":"284","author":"IG Ganley","year":"2009","unstructured":"Ganley IG, Lam DH, Wang J, Ding X, Chen S, Jiang X. ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009;284:12297\u2013305. [cited 2017 Aug 3] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/19258318 . American Society for Biochemistry and Molecular Biology","journal-title":"J Biol Chem"},{"key":"364_CR16","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1124\/jpet.111.185660","volume":"339","author":"L Lindemann","year":"2011","unstructured":"Lindemann L, Jaeschke G, Michalon A, Vieira E, Honer M, Spooren W, et al. CTEP: a novel, potent, long-acting, and orally bioavailable metabotropic glutamate receptor 5 inhibitor. J Pharmacol Exp Ther. 2011;339:474\u201386. [cited 2016 Oct 21] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21849627","journal-title":"J Pharmacol Exp Ther"},{"key":"364_CR17","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1001\/jamapsychiatry.2016.0838","volume":"73","author":"JA Quiroz","year":"2016","unstructured":"Quiroz JA, Tamburri P, Deptula D, Banken L, Beyer U, Rabbia M, et al. Efficacy and safety of basimglurant as adjunctive therapy for major depression. JAMA Psychiatry. 2016;73:675. [cited 2016 Nov 15] Available from: http:\/\/archpsyc.jamanetwork.com\/article.aspx?doi=10.1001\/jamapsychiatry.2016.0838","journal-title":"JAMA Psychiatry"},{"key":"364_CR18","doi-asserted-by":"crossref","first-page":"e06734","DOI":"10.7554\/eLife.06734","volume":"4","author":"T Zhang","year":"2015","unstructured":"Zhang T, Dong K, Liang W, Xu D, Xia H, Geng J, et al. G-protein-coupled receptors regulate autophagy by ZBTB16-mediated ubiquitination and proteasomal degradation of Atg14L. elife. 2015;4:e06734. [cited 2016 Oct 21] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25821988","journal-title":"elife"},{"key":"364_CR19","doi-asserted-by":"publisher","first-page":"25464","DOI":"10.1074\/jbc.M703663200","volume":"282","author":"C EYW","year":"2007","unstructured":"EYW C, Kir S, Tooze SA. siRNA screening of the kinome identifies ULK1 as a multidomain modulator of autophagy. J Biol Chem. 2007;282:25464\u201374. [cited 2017 Aug 3] Available from: http:\/\/www.jbc.org\/lookup\/doi\/10.1074\/jbc.M703663200","journal-title":"J Biol Chem"},{"key":"364_CR20","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1083\/jcb.200712064","volume":"181","author":"T Hara","year":"2008","unstructured":"Hara T, Takamura A, Kishi C, Iemura S, Natsume T, Guan J-L, et al. FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells. J Cell Biol. 2008;181:497\u2013510. [cited 2017 Aug 3] Available from: http:\/\/www.jcb.org\/lookup\/doi\/10.1083\/jcb.200712064","journal-title":"J Cell Biol"},{"key":"364_CR21","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1016\/j.neuint.2006.01.020","volume":"49","author":"G Page","year":"2006","unstructured":"Page G, Khidir FAL, Pain S, Barrier L, Fauconneau B, Guillard O, et al. Group I metabotropic glutamate receptors activate the p70S6 kinase via both mammalian target of rapamycin (mTOR) and extracellular signal-regulated kinase (ERK 1\/2) signaling pathways in rat striatal and hippocampal synaptoneurosomes. Neurochem Int. 2006;49:413\u201321. [cited 2017 Aug 3] Available from: http:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S019701860600088X","journal-title":"Neurochem Int"},{"key":"364_CR22","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1038\/nature04724","volume":"441","author":"T Hara","year":"2006","unstructured":"Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006;441:885\u20139. [cited 2017 Nov 15] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16625204","journal-title":"Nature"},{"key":"364_CR23","doi-asserted-by":"crossref","unstructured":"Orr ME, Oddo S. Autophagic\/lysosomal dysfunction in Alzheimer\u2019s disease. Alzheimers Res Ther. 2013;5:\u201353. [cited 2017 Nov 15] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/24171818","DOI":"10.1186\/alzrt217"},{"key":"364_CR24","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1039\/b804606a","volume":"4","author":"S Sarkar","year":"2008","unstructured":"Sarkar S, Rubinsztein DC. Small molecule enhancers of autophagy for neurodegenerative diseases. Mol BioSyst. 2008;4:895\u2013901. [cited 2017 Jan 11] Available from: http:\/\/xlink.rsc.org\/?DOI=b804606a","journal-title":"Mol BioSyst"},{"key":"364_CR25","doi-asserted-by":"publisher","first-page":"11","DOI":"10.4161\/auto.1.1.1513","volume":"1","author":"DC Rubinsztein","year":"2005","unstructured":"Rubinsztein DC, DiFiglia M, Heintz N, Nixon RA, Qin Z-H, Ravikumar B, et al. Autophagy and its possible roles in nervous system diseases, damage and repair. Autophagy. 2005;1:11\u201322. [cited 2017 Nov 15] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/16874045","journal-title":"Autophagy"},{"key":"364_CR26","doi-asserted-by":"publisher","first-page":"381","DOI":"10.14348\/molcells.2015.0034","volume":"38","author":"J Nah","year":"2015","unstructured":"Nah J, Yuan J, Jung Y-K. Autophagy in neurodegenerative diseases: from mechanism to therapeutic approach. Mol Cells. 2015;38:381\u20139. [cited 2018 Mar 7] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/25896254 . Korean Society for Molecular and Cellular Biology","journal-title":"Mol Cells"},{"key":"364_CR27","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1038\/nm.3232","volume":"19","author":"RA Nixon","year":"2013","unstructured":"Nixon RA. The role of autophagy in neurodegenerative disease. Nat Med. 2013;19:983\u201397. [cited 2018 Mar 7] Available from: http:\/\/www.nature.com\/articles\/nm.3232 . Nature Publishing Group","journal-title":"Nat Med"},{"key":"364_CR28","doi-asserted-by":"publisher","first-page":"133","DOI":"10.5607\/en.2013.22.3.133","volume":"22","author":"K-M Lee","year":"2013","unstructured":"Lee K-M, Hwang S-K, Lee J-A. Neuronal autophagy and neurodevelopmental disorders. Exp Neurobiol. 2013;22:133. [cited 2018 Feb 2] Available from: https:\/\/synapse.koreamed.org\/DOIx.php?id=10.5607\/en.2013.22.3.133","journal-title":"Exp Neurobiol"},{"key":"364_CR29","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1212\/WNL.0b013e3182166dc7","volume":"76","author":"DK Sokol","year":"2011","unstructured":"Sokol DK, Maloney B, Long JM, Ray B, Lahiri DK. Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology. 2011;76:1344\u201352. [cited 2018 Feb 2] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/21482951 . American Academy of Neurology","journal-title":"Neurology"},{"key":"364_CR30","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1093\/hmg\/ddh019","volume":"13","author":"JL Jankowsky","year":"2004","unstructured":"Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, et al. Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum Mol Genet. 2004;13:159\u201370. [cited 2018 Feb 1] Available from: https:\/\/academic.oup.com\/hmg\/article-lookup\/doi\/10.1093\/hmg\/ddh019","journal-title":"Hum Mol Genet"},{"key":"364_CR31","doi-asserted-by":"publisher","first-page":"5196","DOI":"10.1523\/JNEUROSCI.17-13-05196.1997","volume":"17","author":"YM Lu","year":"1997","unstructured":"Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM, et al. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP. J Neurosci. 1997;17:5196\u2013205. [cited 2018 Feb 1]Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/9185557","journal-title":"J Neurosci"},{"key":"364_CR32","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1016\/S0896-6273(03)00434-3","volume":"39","author":"S Oddo","year":"2003","unstructured":"Oddo S, Caccamo A, Shepherd JD, Murphy MP, Golde TE, Kayed R, et al. Triple-transgenic model of Alzheimer\u2019s disease with plaques and tangles: intracellular Abeta and synaptic dysfunction. Neuron. 2003;39:409\u201321. [cited 2018 Feb 1] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/12895417","journal-title":"Neuron"}],"container-title":["Molecular Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-018-0364-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s13041-018-0364-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s13041-018-0364-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,10,16]],"date-time":"2019-10-16T01:54:19Z","timestamp":1571190859000},"score":1,"resource":{"primary":{"URL":"https:\/\/molecularbrain.biomedcentral.com\/articles\/10.1186\/s13041-018-0364-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,10]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,12]]}},"alternative-id":["364"],"URL":"https:\/\/doi.org\/10.1186\/s13041-018-0364-9","relation":{},"ISSN":["1756-6606"],"issn-type":[{"value":"1756-6606","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,10]]},"assertion":[{"value":"8 March 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 March 2018","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 April 2018","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal experiments were conducted in accordance with the University of Western Ontario and University of Ottawa animal care committees.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"19"}}