Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease

Dwight C. German, E. Matthew Quintero, Chang Lin Liang, Benton Ng, Surender Punia, Chonglun Xie, John M. Dietschy

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

The BALB/c mouse model of Niemann-Pick type C (NPC) disease exhibits neuropathological similarities to the human condition. There is an age-related cerebral atrophy, demyelination of the corpus callosum, and degeneration of cerebellar Purkinje cells in the NPC mouse. In human NPC, many cortical and subcortical neurons contain neurofibrillary tangles, which are thought by some investigators to play an important role in the neurodegenerative process. The purpose of the present study was to determine whether neurodegeneration occurs in the NPC mouse, in brain regions other than the cerebellum and whether the degeneration is related to the presence of neurofibrillary tangles. Using light microscopic methods with immunohistochemistry, electron microscopy, and cell counting methods, 11-week-old NPC+/+ and NPC-/- animals were examined. In the NPC-/- mice, there were 96% fewer Purkinje cells, 28% fewer neurons in the prefrontal cortex, 20% fewer neurons in the thalamus, and 63% fewer glial cells in the corpus callosum. On the other hand, previous studies indicate normal numbers of neurons and glial cells in these same neuroanatomical regions in young NPC-/- mice. There were normal numbers of cholinergic neurons in sections assessed in the striatum and basal forebrain in the 11-week-old animals and no evidence of neurofibrillary tangles within cells. The present data indicate that both neurons and glial cells die in the NPC mouse but that all cells are not equally vulnerable. There was no evidence for neurofibrillary tangles in the NPC mouse, and therefore the degenerative process in the mouse is unrelated to the neurofibrillary tangle.

Original languageEnglish (US)
Pages (from-to)415-425
Number of pages11
JournalJournal of Comparative Neurology
Volume433
Issue number3
DOIs
StatePublished - May 7 2001

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Niemann-Pick Diseases
Neurofibrillary Tangles
Neurons
Neuroglia
Corpus Callosum
Purkinje Cells
Type C Niemann-Pick Disease
Cholinergic Neurons
Demyelinating Diseases
Prefrontal Cortex
Thalamus
Cerebellum
Atrophy
Electron Microscopy
Immunohistochemistry
Research Personnel
Light

Keywords

  • Cholinergic neurons
  • Corpus callosum
  • Glial cells
  • Prefrontal cortex
  • Purkinje cells
  • Stereology
  • Thalamus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease. / German, Dwight C.; Matthew Quintero, E.; Liang, Chang Lin; Ng, Benton; Punia, Surender; Xie, Chonglun; Dietschy, John M.

In: Journal of Comparative Neurology, Vol. 433, No. 3, 07.05.2001, p. 415-425.

Research output: Contribution to journalArticle

German, Dwight C. ; Matthew Quintero, E. ; Liang, Chang Lin ; Ng, Benton ; Punia, Surender ; Xie, Chonglun ; Dietschy, John M. / Selective neurodegeneration, without neurofibrillary tangles, in a mouse model of Niemann-Pick C disease. In: Journal of Comparative Neurology. 2001 ; Vol. 433, No. 3. pp. 415-425.
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