{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T18:54:14Z","timestamp":1787165654760,"version":"build-2736575974"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T00:00:00Z","timestamp":1598227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["RG\/14\/4\/30736"],"award-info":[{"award-number":["RG\/14\/4\/30736"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["IRP of NINDS"],"award-info":[{"award-number":["IRP of NINDS"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/13\/5\/29927"],"award-info":[{"award-number":["FS\/13\/5\/29927"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Synuclein (\u03b1, \u03b2, and \u03b3) proteins are highly expressed in presynaptic terminals, and significant data exist supporting their role in regulating neurotransmitter release. Targeting the gene encoding \u03b1-synuclein is the basis of many animal models of Parkinson\u2019s disease (PD). However, the physiological role of this family of proteins in not well understood and could be especially relevant as interfering with accumulation of \u03b1-synuclein level has therapeutic potential in limiting PD progression. The long-term effects of their removal are unknown and given the complex pathophysiology of PD, could exacerbate other clinical features of the disease, for example dysautonomia. In the present study, we sought to characterize the autonomic phenotypes of mice lacking all synucleins (\u03b1, \u03b2, and \u03b3; \u03b1\u03b2\u03b3\u2212\/\u2212) in order to better understand the role of synuclein-family proteins in autonomic function. We probed respiratory and cardiovascular reflexes in conscious and anesthetized, young (4 months) and aged (18\u201320 months) \u03b1\u03b2\u03b3\u2212\/\u2212 male mice. Aged mice displayed impaired respiratory responses to both hypoxia and hypercapnia when breathing activities were recorded in conscious animals using whole-body plethysmography. These animals were also found to be hypertensive from conscious blood pressure recordings, to have reduced pressor baroreflex gain under anesthesia, and showed reduced termination of both pressor and depressor reflexes. The present data demonstrate the importance of synuclein in the normal function of respiratory and cardiovascular reflexes during aging.<\/jats:p>","DOI":"10.3390\/brainsci10090583","type":"journal-article","created":{"date-parts":[[2020,8,24]],"date-time":"2020-08-24T10:37:32Z","timestamp":1598265452000},"page":"583","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Synuclein Deficiency Results in Age-Related Respiratory and Cardiovascular Dysfunctions in Mice"],"prefix":"10.3390","volume":"10","author":[{"given":"Patrick S.","family":"Hosford","sequence":"first","affiliation":[{"name":"Department of Neuroscience Physiology and Pharmacology, Center for Cardiovascular and Metabolic Neuroscience, University College London (UCL), London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Ninkina","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"},{"name":"Institute of Physiologically Active Compounds, Russian Academy of Sciences (IPAC RAS), 1 Severniy proezd, 142432 Chernogolovka, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir L.","family":"Buchman","sequence":"additional","affiliation":[{"name":"School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK"},{"name":"Institute of Physiologically Active Compounds, Russian Academy of Sciences (IPAC RAS), 1 Severniy proezd, 142432 Chernogolovka, Moscow Region, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nephtali","family":"Marina","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Physiology and Pharmacology, Center for Cardiovascular and Metabolic Neuroscience, University College London (UCL), London WC1E 6BT, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4119-9979","authenticated-orcid":false,"given":"Shahriar","family":"SheikhBahaei","sequence":"additional","affiliation":[{"name":"Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892, USA"},{"name":"Neuron-Glia Signaling and Circuits Unit, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH), Bethesda, MD 20892, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1002\/(SICI)1097-4547(19991001)58:1<120::AID-JNR12>3.0.CO;2-E","article-title":"Synucleins in synaptic plasticity and neurodegenerative disorders","volume":"58","author":"Clayton","year":"1999","journal-title":"J. Neurosci. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1663","DOI":"10.1126\/science.1195227","article-title":"\u03b1-Synuclein promotes SNARE-complex assembly in vivo and in vitro","volume":"329","author":"Sharma","year":"2010","journal-title":"Science"},{"key":"ref_3","first-page":"699","article-title":"The Synaptic Function of \u03b1-Synuclein","volume":"5","year":"2015","journal-title":"J. Park. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1126\/science.276.5321.2045","article-title":"Mutation in the \u03b1-Synuclein Gene Identified in Families with Parkinson\u2019s Disease","volume":"276","author":"Polymeropoulos","year":"1997","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.tins.2016.09.003","article-title":"\u03b1-Synuclein-Based Animal Models of Parkinson\u2019s Disease: Challenges and Opportunities in a New Era","volume":"39","author":"Visanji","year":"2016","journal-title":"Trends Neurosci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/j.tins.2010.09.004","article-title":"\u03b1-Synuclein and dopamine at the crossroads of Parkinson\u2019s disease","volume":"33","author":"Venda","year":"2010","journal-title":"Trends Neurosci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"14966","DOI":"10.1073\/pnas.0406283101","article-title":"Double-knockout mice for alpha- and beta-synucleins: Effect on synaptic functions","volume":"101","author":"Chandra","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/j.1471-4159.2004.02378.x","article-title":"Developmental loss and resistance to MPTP toxicity of dopaminergic neurones in substantia nigra pars compacta of \u03b3-synuclein, \u03b1-synuclein and double \u03b1\/\u03b3-synuclein null mutant mice","volume":"89","author":"Robertson","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2804","DOI":"10.1523\/JNEUROSCI.08-08-02804.1988","article-title":"Synuclein: A neuron-specific protein localized to the nucleus and presynaptic nerve terminal","volume":"8","author":"Maroteaux","year":"1988","journal-title":"J. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1016\/j.neurobiolaging.2008.11.001","article-title":"Absence of \u03b1-synuclein affects dopamine metabolism and synaptic markers in the striatum of aging mice","volume":"31","author":"Ninkina","year":"2010","journal-title":"Neurobiol. Aging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.neurobiolaging.2016.06.020","article-title":"Combinational losses of synucleins reveal their differential requirements for compensating age-dependent alterations in motor behavior and dopamine metabolism","volume":"46","author":"Peters","year":"2016","journal-title":"Neurobiol. Aging"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neurobiolaging.2020.02.026","article-title":"Alterations in the nigrostriatal system following conditional inactivation of \u03b1-synuclein in neurons of adult and aging mice","volume":"91","author":"Ninkina","year":"2020","journal-title":"Neurobiol. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"19573","DOI":"10.1073\/pnas.1005005107","article-title":"\u03b1\u03b2\u03b3-Synuclein triple knockout mice reveal age-dependent neuronal dysfunction","volume":"107","author":"Polydoro","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7264","DOI":"10.1523\/JNEUROSCI.6194-10.2011","article-title":"Functional alterations to the nigrostriatal system in mice lacking all three members of the synuclein family","volume":"31","author":"Anwar","year":"2011","journal-title":"J. Neurosci."},{"key":"ref_15","first-page":"207","article-title":"Impact of autonomic dysfunctions on the quality of life in Parkinson\u2019s disease patients","volume":"117","author":"Rajkovaca","year":"2016","journal-title":"Acta Neurol. Belg."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1002\/mds.27268","article-title":"Autonomic dysfunction in Parkinson\u2019s disease: A prospective cohort study","volume":"33","author":"Merola","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"s32","DOI":"10.1007\/s100720300035","article-title":"Autonomic dysfunction in Parkinson\u2019s disease","volume":"24","author":"Micieli","year":"2003","journal-title":"Neurol. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/S0197-4580(02)00065-9","article-title":"Staging of brain pathology related to sporadic Parkinson\u2019s disease","volume":"24","author":"Braak","year":"2003","journal-title":"Neurobiol. Aging"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00401-007-0193-x","article-title":"Parkinson\u2019s disease: Lesions in dorsal horn layer I, involvement of parasympathetic and sympathetic pre- and postganglionic neurons","volume":"113","author":"Braak","year":"2007","journal-title":"Acta Neuropathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1212\/01.WNL.0000138500.73671.DC","article-title":"Autonomic failure as the initial presentation of Parkinson disease and dementia with Lewy bodies","volume":"63","author":"Kaufmann","year":"2004","journal-title":"Neurology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10286-018-00584-7","article-title":"Autonomic dysfunction in Parkinson disease and animal models","volume":"29","author":"Metzger","year":"2019","journal-title":"Clin. Auton. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2170\/jjphysiol.47.317","article-title":"Determination of Ventilatory Volume in Mice by Whole Body Plethysmography","volume":"47","author":"Onodera","year":"1997","journal-title":"Jpn. J. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.resp.2017.08.001","article-title":"Respiratory rhythm irregularity after carotid body denervation in rats","volume":"246","author":"Sheikhbahaei","year":"2017","journal-title":"Respir. Physiol. Neurobiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/s41467-017-02723-6","article-title":"Astrocytes modulate brainstem respiratory rhythm-generating circuits and determine exercise capacity","volume":"9","author":"Sheikhbahaei","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1038\/ajh.2008.301","article-title":"Validation of Volume-Pressure Recording Tail-Cuff Blood Pressure Measurements","volume":"21","author":"Feng","year":"2008","journal-title":"Am. J. Hypertens."},{"key":"ref_26","first-page":"386","article-title":"The Hidden Cost of Housing Practices: Using Noninvasive Imaging to Quantify the Metabolic Demands of Chronic Cold Stress of Laboratory Mice","volume":"63","author":"David","year":"2013","journal-title":"Comp. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2160","DOI":"10.1002\/mds.23948","article-title":"Parkinson\u2019s disease and \u03b1-synuclein expression","volume":"26","author":"Devine","year":"2011","journal-title":"Mov. Disord."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1146\/annurev-genom-082410-101440","article-title":"Recent advances in the genetics of Parkinson\u2019s disease","volume":"12","author":"Martin","year":"2011","journal-title":"Annu. Rev. Genom. Hum. Genet."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000354615","article-title":"\u03b1-Synuclein in Parkinson\u2019s disease: Pathogenic function and translation into animal models","volume":"14","author":"Eschbach","year":"2014","journal-title":"Neurodegener. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"a009324","DOI":"10.1101\/cshperspect.a009324","article-title":"Animal Models of Parkinson\u2019s Disease: Vertebrate Genetics","volume":"2","author":"Lee","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.brainresbull.2011.07.019","article-title":"Genetically engineered mouse models of Parkinson\u2019s disease","volume":"88","author":"Crabtree","year":"2012","journal-title":"Brain Res. Bull."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/S1474-4422(11)70227-7","article-title":"Modelling of Parkinson\u2019s disease in mice","volume":"10","author":"Chesselet","year":"2011","journal-title":"Lancet Neurol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1111\/j.1476-5381.2011.01426.x","article-title":"Animal models of Parkinson\u2019s disease: A source of novel treatments and clues to the cause of the disease","volume":"164","author":"Duty","year":"2011","journal-title":"Br. J. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.neulet.2010.09.061","article-title":"Mitochondrial alpha-synuclein accumulation impairs complex I function in dopaminergic neurons and results in increased mitophagy in vivo","volume":"486","author":"Chinta","year":"2010","journal-title":"Neurosci. Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s12035-013-8394-x","article-title":"\u03b1-Synuclein and mitochondrial dysfunction in Parkinson\u2019s disease","volume":"47","author":"Mullin","year":"2013","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.freeradbiomed.2013.03.018","article-title":"Mitochondrial Diseases of the Brain","volume":"63","author":"Chaturvedi","year":"2013","journal-title":"Free Radic. Boil. Med."},{"key":"ref_37","first-page":"342ra78","article-title":"\u03b1-Synuclein binds to TOM20 and inhibits mitochondrial protein import in Parkinson\u2019s disease","volume":"8","author":"Barrett","year":"2016","journal-title":"Sci. Transl. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10460","DOI":"10.1523\/JNEUROSCI.0045-15.2015","article-title":"Functional Oxygen Sensitivity of Astrocytes","volume":"35","author":"Angelova","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1152\/japplphysiol.00194.2017","article-title":"On the existence of a central respiratory oxygen sensor","volume":"123","author":"Gourine","year":"2017","journal-title":"J. Appl. Physiol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1126\/science.1683005","article-title":"Pre-Botzinger complex: A brainstem region that may generate respiratory rhythm in mammals","volume":"254","author":"Smith","year":"1991","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/s41583-018-0003-6","article-title":"Breathing matters","volume":"19","author":"Funk","year":"2018","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3245","DOI":"10.1113\/JP274727","article-title":"Release of ATP by pre-B\u00f6tzinger complex astrocytes contributes to the hypoxic ventilatory response via a Ca2+ -dependent P2Y1 receptor mechanism","volume":"596","author":"Rajani","year":"2017","journal-title":"J. Physiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"10510","DOI":"10.1523\/JNEUROSCI.1659-16.2016","article-title":"Monomeric Alpha-Synuclein Exerts a Physiological Role on Brain ATP Synthase","volume":"36","author":"Ludtmann","year":"2016","journal-title":"J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s13311-013-0182-9","article-title":"\u03b1-Synuclein and Mitochondria: Partners in Crime?","volume":"10","author":"Nakamura","year":"2013","journal-title":"Neurotherapeutics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.neuroscience.2015.03.048","article-title":"Respiratory deficits in a rat model of Parkinson\u2019s disease","volume":"297","author":"Tuppy","year":"2015","journal-title":"Neuroscience"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.lfs.2017.05.020","article-title":"Phrenic and hypoglossal nerve activity during respiratory response to hypoxia in 6-OHDA unilateral model of Parkinson\u2019s disease","volume":"180","author":"Andrzejewski","year":"2017","journal-title":"Life Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.expneurol.2017.04.006","article-title":"Role of the locus coeruleus catecholaminergic neurons in the chemosensory control of breathing in a Parkinson\u2019s disease model","volume":"293","author":"Oliveira","year":"2017","journal-title":"Exp. Neurol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.expneurol.2018.01.003","article-title":"The involvement of the pathway connecting the substantia nigra, the periaqueductal gray matter and the retrotrapezoid nucleus in breathing control in a rat model of Parkinson\u2019s disease","volume":"302","author":"Lima","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1113\/EP087507","article-title":"Respiratory disturbances in a mouse model of Parkinson\u2019s disease","volume":"104","author":"Oliveira","year":"2019","journal-title":"Exp. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2285","DOI":"10.1016\/j.hrthm.2015.06.005","article-title":"Control of ventricular excitability by neurons of the dorsal motor nucleus of the vagus nerve","volume":"12","author":"Machhada","year":"2015","journal-title":"Hear. Rhythm."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1093\/cvr\/cvv249","article-title":"Age-dependent blood pressure elevation is due to increased vascular smooth muscle tone mediated by G-protein signaling","volume":"109","author":"Wirth","year":"2015","journal-title":"Cardiovasc. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1097\/HJH.0000000000001871","article-title":"Long-term stimulation of cardiac vagal preganglionic neurons reduces blood pressure in the spontaneously hypertensive rat","volume":"36","author":"Moreira","year":"2018","journal-title":"J. Hypertens."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"S127","DOI":"10.1111\/j.1447-0594.2010.00592.x","article-title":"Aging of the autonomic nervous system and possible improvements in autonomic activity using somatic afferent stimulation","volume":"10","author":"Hotta","year":"2010","journal-title":"Geriatr. Gerontol. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1161\/CIRCRESAHA.114.302524","article-title":"The Autonomic Nervous System and Hypertension","volume":"114","author":"Mancia","year":"2014","journal-title":"Circ. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1002\/mds.27344","article-title":"Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies","volume":"33","author":"Palma","year":"2018","journal-title":"Mov. Disord."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"910","DOI":"10.1161\/HYPERTENSIONAHA.118.12642","article-title":"Alpha-Synuclein Deposition Within Sympathetic Noradrenergic Neurons Is Associated With Myocardial Noradrenergic Deficiency in Neurogenic Orthostatic Hypotension","volume":"73","author":"Isonaka","year":"2019","journal-title":"Hypertension"}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/9\/583\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:05:32Z","timestamp":1760177132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/10\/9\/583"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,8,24]]},"references-count":56,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2020,9]]}},"alternative-id":["brainsci10090583"],"URL":"https:\/\/doi.org\/10.3390\/brainsci10090583","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,8,24]]}}}