{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:50:34Z","timestamp":1790769034107,"version":"4.1.0"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T00:00:00Z","timestamp":1561680000000},"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."],"DOI":"10.3389\/fnins.2019.00669","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T06:06:41Z","timestamp":1561702001000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":60,"title":["Huntington\u2019s Disease Patient-Derived Astrocytes Display Electrophysiological Impairments and Reduced Neuronal Support"],"prefix":"10.3389","volume":"13","author":[{"given":"Veronica J.","family":"Garcia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Rushton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colton M.","family":"Tom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas D.","family":"Allen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kemp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clive N.","family":"Svendsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virginia B.","family":"Mattis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2019,6,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/(sici)1097-0029(19981001)43:1\u00a129::aid-jemt5\u00bf3.0.co;2-h","article-title":"Astrocyte changes in aging cerebral cortex and hippocampus: a quantitative immunohistochemical study.","volume":"43","author":"Amenta","year":"1998","journal-title":"Microsc. Res. Tech."},{"key":"B2","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1038\/ng0893-398","article-title":"The relationship between trinucleotide (CAG) repeat length.","volume":"4","author":"Andrew","year":"1993","journal-title":"Nat. Genet."},{"key":"B3","author":"Aschner","year":"1996","journal-title":"The Role of Glia in Neurotoxicity."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms11758","article-title":"Human glia can both induce and rescue aspects of disease phenotype in Huntington disease.","volume":"7","author":"Benraiss","year":"2016","journal-title":"Nat. Commun."},{"key":"B5","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1152\/jn.1997.78.1.461","article-title":"Postnatal development of ionic currents in rat hippocampal astrocytes in situ.","volume":"78","author":"Bordey","year":"1997","journal-title":"J. Neurophysiol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"22480","DOI":"10.1073\/pnas.0911503106","article-title":"Expression of mutant huntingtin in mouse brain astrocytes causes age-dependent neurological symptoms.","volume":"106","author":"Bradford","year":"2009","journal-title":"Proc. Natl. Acad Sci. U.S.A."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020370","article-title":"Astrocytes control synapse formation, function, and elimination.","volume":"7","author":"Chung","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.scr.2013.01.009","article-title":"EZ spheres: a stable and expandable culture system for the generation of pre-rosette multipotent stem cells from human ESCs and iPSCs.","volume":"10","author":"Ebert","year":"2013","journal-title":"Stem Cell Res."},{"key":"B9","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/nature07677","article-title":"Induced pluripotent stem cells from a spinal muscular atrophy patient.","volume":"457","author":"Ebert","year":"2009","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"3053","DOI":"10.1093\/hmg\/ddq212","article-title":"In vivo expression of polyglutamine-expanded huntingtin by mouse striatal astrocytes impairs glutamate transport: a correlation with Huntington\u2019s disease subjects.","volume":"19","author":"Faideau","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.stem.2012.04.027","article-title":"Induced pluripotent stem cells from patients with Huntington\u2019s disease show CAG-repeat-expansion-associated phenotypes.","volume":"11","year":"2012","journal-title":"Cell Stem Cell"},{"key":"B12","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/nn.4532","article-title":"Developmental alterations in Huntington\u2019s disease neural cells and pharmacological rescue in cells and mice.","volume":"20","year":"2017","journal-title":"Nat. Neurosci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"C922","DOI":"10.1152\/ajpcell.2001.281.3.C922","article-title":"An inwardly rectifying K(+) channel, Kir4.1, expressed in astrocytes surrounds synapses and blood vessels in brain.","volume":"281","author":"Higashi","year":"2001","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1038\/nn.4345","article-title":"ALS disrupts spinal motor neuron maturation and aging pathways within gene co-expression networks.","volume":"19","author":"Ho","year":"2016","journal-title":"Nat. Neurosci."},{"key":"B15","doi-asserted-by":"publisher","first-page":"4328","DOI":"10.1093\/hmg\/ddu151","article-title":"Inhibition of soluble tumor necrosis factor is therapeutic in Huntington\u2019s disease.","volume":"23","author":"Hsiao","year":"2014","journal-title":"Hum. Mol. Genet."},{"key":"B16","doi-asserted-by":"publisher","first-page":"3453","DOI":"10.1523\/JNEUROSCI.3693-15.2016","article-title":"Dysfunctional calcium and glutamate signaling in striatal astrocytes from Huntington\u2019s disease model mice.","volume":"36","author":"Jiang","year":"2016","journal-title":"J. Neurosci."},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024240","article-title":"Huntington\u2019s Disease: mechanisms of pathogenesis and therapeutic strategies.","volume":"7","author":"Jimenez-Sanchez","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B18","doi-asserted-by":"publisher","first-page":"886","DOI":"10.1038\/nm.3639","article-title":"GABA from reactive astrocytes impairs memory in mouse models of Alzheimer\u2019s disease.","volume":"20","author":"Jo","year":"2014","journal-title":"Nat. Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"3069","DOI":"10.1523\/JNEUROSCI.4562-06.2007","article-title":"Functional neural development from human embryonic stem cells: accelerated synaptic activity via astrocyte coculture.","volume":"27","author":"Johnson","year":"2007","journal-title":"J. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-5-17","article-title":"Astrocytes generated from patient induced pluripotent stem cells recapitulate features of Huntington\u2019s disease patient cells.","volume":"5","author":"Juopperi","year":"2012","journal-title":"Mol. brain"},{"key":"B21","doi-asserted-by":"publisher","first-page":"6583","DOI":"10.1113\/JP270655","article-title":"Improving and accelerating the differentiation and functional maturation of human stem cell-derived neurons: role of extracellular calcium and GABA.","volume":"594","author":"Kemp","year":"2016","journal-title":"J. Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.tins.2017.05.002","article-title":"Unravelling and exploiting astrocyte dysfunction in Huntington\u2019s disease.","volume":"40","author":"Khakh","year":"2017","journal-title":"Trends Neurosci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1021\/cn500100r","article-title":"Astrocytes and Huntington\u2019s disease.","volume":"5","author":"Khakh","year":"2014","journal-title":"ACS Chem. Neurosci."},{"key":"B24","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1002\/1097-4547(20000915)61:6\u00a1577::aid-jnr1\u00bf3.0.co;2-t","article-title":"Freshly isolated astrocyte (FIA) preparations: a useful single cell system for studying astrocyte properties.","volume":"61","author":"Kimelberg","year":"2000","journal-title":"J. Neurosci. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1016\/j.neuroscience.2004.06.008","article-title":"Potassium buffering in the central nervous system.","volume":"129","author":"Kofuji","year":"2004","journal-title":"Neuroscience"},{"key":"B26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.brainres.2010.04.057","article-title":"Electrophysiological properties of subventricular zone cells in adult mouse brain.","volume":"1340","author":"Lai","year":"2010","journal-title":"Brain Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1002\/glia.21087","article-title":"Astrocytes are GABAergic cells that modulate microglial activity.","volume":"59","author":"Lee","year":"2011","journal-title":"Glia"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5780","DOI":"10.1074\/jbc.M704704200","article-title":"Calcium homeostasis and mitochondrial dysfunction in striatal neurons of Huntington disease.","volume":"283","author":"Lim","year":"2008","journal-title":"J. Biol. Chem."},{"key":"B29","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1006\/nbdi.2002.0528","article-title":"Pyramidal cell loss in motor cortices in Huntington\u2019s disease.","volume":"10","author":"Macdonald","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"5245","DOI":"10.1523\/jneurosci.20-14-05245.2000","article-title":"Modulation of Kv1.5 currents by src tyrosine phosphorylation: potential role in the differentiation of astrocytes.","volume":"20","author":"MacFarlane","year":"2000","journal-title":"J. Neurosci."},{"key":"B31","doi-asserted-by":"publisher","first-page":"3257","DOI":"10.1093\/hmg\/ddv080","article-title":"HD iPSC-derived neural progenitors accumulate in culture and are susceptible to BDNF withdrawal due to glutamate toxicity.","volume":"24","author":"Mattis","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"B32","doi-asserted-by":"publisher","first-page":"6850","DOI":"10.1523\/jneurosci.17-18-06850.1997","article-title":"Heterogeneity of astrocyte resting membrane potentials and intercellular coupling revealed by whole-cell and gramicidin-perforated patch recordings from cultured neocortical and hippocampal slice astrocytes.","volume":"17","author":"McKhann","year":"1997","journal-title":"J. Neurosci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1016\/j.neuron.2010.01.008","article-title":"Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington\u2019s disease mice.","volume":"65","author":"Milnerwood","year":"2010","journal-title":"Neuron"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.5349.2","article-title":"Immunofluorescent visualization of mouse interneuron subtypes.","volume":"3","author":"Molgaard","year":"2014","journal-title":"F1000Res."},{"key":"B35","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1634\/stemcells.2007-0299","article-title":"A high concentration of epidermal growth factor increases the growth and survival of neurogenic radial glial cells within human neurosphere cultures.","volume":"26","author":"Nelson","year":"2008","journal-title":"Stem Cells"},{"key":"B36","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.brainresrev.2009.11.002","article-title":"Role of glial cells in the formation and maintenance of synapses.","volume":"63","author":"Pfrieger","year":"2010","journal-title":"Brain Res. Rev."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1684","DOI":"10.1126\/science.277.5332.1684","article-title":"Synaptic efficacy enhanced by glial cells in vitro.","volume":"277","author":"Pfrieger","year":"1997","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1152\/jn.1995.73.1.333","article-title":"Biophysical and pharmacological characterization of inwardly rectifying K+ currents in rat spinal cord astrocytes.","volume":"73","author":"Ransom","year":"1995","journal-title":"J. Neurophysiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1002\/glia.20445","article-title":"S100B expression defines a state in which GFAP-expressing cells lose their neural stem cell potential and acquire a more mature developmental stage.","volume":"55","author":"Raponi","year":"2007","journal-title":"Glia"},{"key":"B40","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1016\/j.stemcr.2015.11.005","article-title":"genomic analysis reveals disruption of striatal neuronal development and therapeutic targets in human Huntington\u2019s disease neural stem cells.","volume":"5","author":"Ring","year":"2015","journal-title":"Stem Cell Rep."},{"key":"B41","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1016\/S1474-4422(10)70245-3","article-title":"Huntington\u2019s disease: from molecular pathogenesis to clinical treatment.","volume":"10","author":"Ross","year":"2011","journal-title":"Lancet Neurol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"7474","DOI":"10.1523\/JNEUROSCI.3790-08.2009","article-title":"Analysis of astroglial K+ channel expression in the developing hippocampus reveals a predominant role of the Kir4.1 subunit.","volume":"29","author":"Seifert","year":"2009","journal-title":"J. Neurosci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1002\/(sici)1098-1136(199903)26:1\u00a11::aid-glia1\u00bf3.0.co;2-z","article-title":"Mature hippocampal astrocytes exhibit functional metabotropic and ionotropic glutamate receptors in situ.","volume":"26","author":"Shelton","year":"1999","journal-title":"Glia"},{"key":"B44","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1083\/jcb.200508072","article-title":"Expression of mutant huntingtin in glial cells contributes to neuronal excitotoxicity.","volume":"171","author":"Shin","year":"2005","journal-title":"J. Cell Biol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"2211","DOI":"10.1016\/j.celrep.2018.04.052","article-title":"Integrative characterization of the R6\/2 mouse model of huntington\u2019s disease reveals dysfunctional astrocyte metabolism.","volume":"23","author":"Skotte","year":"2018","journal-title":"Cell Rep."},{"key":"B46","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/glia.440110210","article-title":"Voltage-dependent ion channels in glial cells.","volume":"11","author":"Sontheimer","year":"1994","journal-title":"Glia"},{"key":"B47","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1038\/nnano.2012.265","article-title":"Multi-electrode array technologies for neuroscience and cardiology.","volume":"8","author":"Spira","year":"2013","journal-title":"Nat. Nanotechnol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/j.cell.2006.07.024","article-title":"Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors.","volume":"126","author":"Takahashi","year":"2006","journal-title":"Cell"},{"key":"B49","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/j.scr.2013.05.002","article-title":"Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells.","volume":"11","author":"Tang","year":"2013","journal-title":"Stem Cell Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"C520","DOI":"10.1152\/ajpcell.00166.2015","article-title":"Forced cell cycle exit and modulation of GABAA, CREB, and GSK3\u03b2 signaling promote functional maturation of induced pluripotent stem cell-derived neurons.","volume":"310","author":"Telezhkin","year":"2016","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1093\/brain\/awq047","article-title":"Cell loss in the motor and cingulate cortex correlates with symptomatology in Huntington\u2019s disease.","volume":"133","author":"Thu","year":"2010","journal-title":"Brain"},{"key":"B52","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nn.3691","article-title":"Astrocyte Kir4.1 ion channel deficits contribute to neuronal dysfunction in Huntington\u2019s disease model mice.","volume":"17","author":"Tong","year":"2014","journal-title":"Nat. Neurosci."},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fncir.2013.00188","article-title":"Reduced tonic inhibition in striatal output neurons from Huntington mice due to loss of astrocytic GABA release through GAT-3.","volume":"7","author":"W\u00f3jtowicz","year":"2013","journal-title":"Front. Neural. Circuits"},{"key":"B54","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1046\/j.1471-4159.2003.01826.x","article-title":"Gene expression in human neural stem cells: effects of leukemia inhibitory factor.","volume":"86","author":"Wright","year":"2003","journal-title":"J. Neurochem."},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1186\/1756-6606-4-42","article-title":"The amount of astrocytic GABA positively correlates with the degree of tonic inhibition in hippocampal CA1 and cerebellum.","volume":"4","author":"Yoon","year":"2011","journal-title":"Mol. Brain"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1186\/s13041-016-0213-7","article-title":"Electrophysiological behavior of neonatal astrocytes in hippocampal stratum radiatum.","volume":"9","author":"Zhong","year":"2016","journal-title":"Mol. Brain"},{"key":"B57","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1152\/jn.00570.2005","article-title":"Development of GLAST(+) astrocytes and NG2(+) glia in rat hippocampus CA1: mature astrocytes are electrophysiologically passive.","volume":"95","author":"Zhou","year":"2006","journal-title":"J. Neurophysiol."}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fnins.2019.00669\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T06:06:44Z","timestamp":1561702004000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fnins.2019.00669\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,28]]},"references-count":57,"alternative-id":["10.3389\/fnins.2019.00669"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2019.00669","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,28]]},"article-number":"669"}}