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

Neurobiol Dis. 2007 Jan;25(1):150-62. doi: 10.1016/j.nbd.2006.09.001. Epub 2006 Oct 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / pathology
  • Animals
  • Astrocytes / pathology
  • Atrophy / pathology
  • Cerebral Cortex / pathology*
  • Disease Models, Animal
  • Disease Progression
  • Electroencephalography
  • Gliosis / pathology
  • Interneurons / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Fluorescence
  • Neuroglia / pathology
  • Neuronal Ceroid-Lipofuscinoses / pathology*
  • Neurons / pathology*
  • Phenotype
  • Seizures / etiology
  • Synapses / pathology
  • Thalamic Nuclei / pathology
  • Thalamus / pathology*
  • Thiolester Hydrolases / genetics
  • Thiolester Hydrolases / physiology*


  • Thiolester Hydrolases
  • palmitoyl-protein thioesterase