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Children with <jats:styled-content style=\"fixed-case\">JNCL<\/jats:styled-content> experience progressive visual, cognitive, and motor deterioration with a decreased life expectancy (late teens\u2010early 20s). Neuronal loss is thought to occur, in part, via glutamate excitotoxicity; however, little is known about astrocyte glutamate regulation in <jats:styled-content style=\"fixed-case\">JNCL<\/jats:styled-content>. Spontaneous Ca<jats:sup>2+<\/jats:sup> oscillations were reduced in murine <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes, which were also observed following glutamate or cytokine exposure. Astrocyte glutamate transport is an energy\u2010demanding process and disruptions in metabolic pathways could influence glutamate homeostasis in <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes. Indeed, basal mitochondrial respiration and <jats:styled-content style=\"fixed-case\">ATP<\/jats:styled-content> production were significantly reduced in <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes. These changes were not attributable to reduced mitochondria, since mitochondrial <jats:styled-content style=\"fixed-case\">DNA<\/jats:styled-content> levels were similar between wild type and <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes. Interestingly, despite these functional deficits in <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes, glutamate transporter expression and glutamate uptake were not dramatically affected. Concurrent with impaired astrocyte metabolism and Ca<jats:sup>2+<\/jats:sup> signaling, murine <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> neurons were hyper\u2010responsive to glutamate, as reflected by heightened and prolonged Ca<jats:sup>2+<\/jats:sup> signals. These findings identify intrinsic metabolic and Ca<jats:sup>2+<\/jats:sup> signaling defects in <jats:italic>Cln3<\/jats:italic><jats:sup><jats:italic>\u0394ex7\/8<\/jats:italic><\/jats:sup> astrocytes that may contribute to neuronal dysfunction in CLN3 disease.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14545-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/onlinelibrary.wiley.com\/page\/journal\/14714159\/homepage\/virtual_issues.htm\">This article is part of the Special Issue \u201cLysosomal Storage Disorders\u201d<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14545","type":"journal-article","created":{"date-parts":[[2018,7,2]],"date-time":"2018-07-02T15:08:30Z","timestamp":1530544110000},"page":"612-624","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Astrocytes in juvenile neuronal ceroid lipofuscinosis (CLN3) display metabolic and calcium signaling abnormalities"],"prefix":"10.1111","volume":"148","author":[{"given":"Megan E.","family":"Bosch","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of Nebraska Medical Center Omaha Nebraska USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7624-670X","authenticated-orcid":false,"given":"Tammy","family":"Kielian","sequence":"additional","affiliation":[{"name":"Department of Pathology and Microbiology University of Nebraska Medical Center 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