Astrocytes in juvenile neuronal ceroid lipofuscinosis (CLN3) display metabolic and calcium signaling abnormalities

Megan E. Bosch, Tammy Kielian

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Juvenile neuronal ceroid lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in ceroid lipofuscinosis 3 (CLN3). Children with JNCL experience progressive visual, cognitive, and motor deterioration with a decreased life expectancy (late teens-early 20s). Neuronal loss is thought to occur, in part, via glutamate excitotoxicity; however, little is known about astrocyte glutamate regulation in JNCL. Spontaneous Ca 2+ oscillations were reduced in murine Cln3 Δex7/8 astrocytes, which were also observed following glutamate or cytokine exposure. Astrocyte glutamate transport is an energy-demanding process and disruptions in metabolic pathways could influence glutamate homeostasis in Cln3 Δex7/8 astrocytes. Indeed, basal mitochondrial respiration and ATP production were significantly reduced in Cln3 Δex7/8 astrocytes. These changes were not attributable to reduced mitochondria, since mitochondrial DNA levels were similar between wild type and Cln3 Δex7/8 astrocytes. Interestingly, despite these functional deficits in Cln3 Δex7/8 astrocytes, glutamate transporter expression and glutamate uptake were not dramatically affected. Concurrent with impaired astrocyte metabolism and Ca 2+ signaling, murine Cln3 Δex7/8 neurons were hyper-responsive to glutamate, as reflected by heightened and prolonged Ca 2+ signals. These findings identify intrinsic metabolic and Ca 2+ signaling defects in Cln3 Δex7/8 astrocytes that may contribute to neuronal dysfunction in CLN3 disease. (Figure presented.). This article is part of the Special Issue “Lysosomal Storage Disorders”.

Original languageEnglish (US)
Pages (from-to)612-624
Number of pages13
JournalJournal of Neurochemistry
Issue number5
StatePublished - Mar 2019


  • Astrocyte
  • CLN3
  • calcium signaling
  • mitochondrial dysfunction

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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