Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6)

Manfred J. Oswald, David N. Palmer, Graham W. Kay, Stephen J.A. Shemilt, Payam Rezaie, Jonathan D. Cooper

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

The neuronal ceroid lipofuscinoses (NCLs, Batten disease) are fatal inherited neurodegenerative diseases characterized by gross brain atrophy, blindness, and intracellular accumulation of lysosome-derived storage bodies. A CLN6 form in sheep is studied as a large animal model of the human diseases. This study describes neuropathological changes in brains from presymptomatic affected sheep. Activated astrocytes and focal clusters of activated microglia were present in outer layers of occipital and somatosensory cortical regions as early as 12 days of age, together with activated perivascular macrophages. Astrocytic activation and progressive transformation of microglia to brain macrophages preceded neurodegeneration and spread to different cortical areas, most prominently in regions associated with clinical symptoms. In contrast, storage body accumulation was much more evenly spread across regions. These data support suggestions that neurodegeneration and storage body accumulation may be independent manifestations of CLN6 mutation and indicate that glial cell activation may be an important mediator in pathogenesis.

Original languageEnglish
Pages (from-to)49-63
Number of pages15
JournalNeurobiology of Disease
Volume20
Issue number1
DOIs
StatePublished - Oct 1 2005
Externally publishedYes

Keywords

  • Astrocytosis
  • Batten disease
  • Brain macrophages
  • Fluorescent
  • Lysosomal storage disease
  • Microglia
  • NCL
  • Neuropathology
  • Storage body accumulation
  • Subunit c

Fingerprint Dive into the research topics of 'Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6)'. Together they form a unique fingerprint.

  • Cite this