Late onset neurodegeneration in the Cln3 -/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation

Charlie C. Pontikis, Claire V. Cella, Nisha Parihar, Ming J. Lim, Shubhodeep Chakrabarti, Hannah M. Mitchison, William C. Mobley, Payam Rezaie, David A. Pearce, Jonathan D. Cooper

Research output: Contribution to journalArticlepeer-review

127 Scopus citations

Abstract

Mouse models of neuronal ceroid lipofuscinosis (NCL) exhibit many features of the human disorder, with widespread regional atrophy and significant loss of GABAergic interneurons in the hippocampus and neocortex. Reactive gliosis is a characteristic of all forms of NCL, but it is unclear whether glial activation precedes or is triggered by neuronal loss. To explore this issue we undertook detailed morphological characterization of the Cln3 null mutant (Cln3- /-) mouse model of juvenile NCL (JNCL) that revealed a delayed onset neurodegenerative phenotype with no significant regional atrophy, but with widespread loss of hippocampal interneurons that was first evident at 14 months of age. Quantitative image analysis demonstrated upregulation of markers of astrocytic and microglial activation in presymptomatic Cln3 -/- mice at 5 months of age, many months before significant neuronal loss occurs. These data provide evidence for subtle glial responses early in JNCL pathogenesis.

Original languageEnglish
Pages (from-to)231-242
Number of pages12
JournalBrain Research
Volume1023
Issue number2
DOIs
StatePublished - Oct 15 2004

Keywords

  • Astrocytosis
  • CLN3
  • GABAergic interneuron
  • JNCL
  • Microglial activation

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