Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis

Catherine Kielar, Lucy Maddox, Ellen Bible, Charlie C. Pontikis, Shannon L. Macauley, Megan A. Griffey, Michael Wong, Mark S. Sands, Jonathan D. Cooper

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.

Original languageEnglish
Pages (from-to)150-162
Number of pages13
JournalNeurobiology of Disease
Issue number1
StatePublished - Jan 2007

Bibliographical note

Funding Information:
These studies were supported by National Institutes of Health grants NS41930 (JDC), NS043205 (MSS), European Commission 6th Framework Research Grant LSHM-CT-2003-503051 (JDC). The following non-profit agencies also contributed financially to this work: The Batten Disease Support and Research Association (MSS, JDC, CK, EB), The Natalie Fund (JDC), The Batten Disease Family Association (JDC) and the Remy Fund (JDC). We would like to thank the other members of the PSDL for their valuable contributions; Noreen Alexander for her expert advice; Drs. David Pearce, Jaana Tyynelä, Tomas Gillingwater, Gerald Finnerty and Alison Barnwell for constructive comments on the manuscript.


  • Batten disease
  • GABAergic interneurons
  • Infantile neuronal ceroid lipofuscinosis
  • Lysosomal storage disorder
  • PPT1
  • Seizures
  • Thalamic neurodegeneration

ASJC Scopus subject areas

  • Neurology


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