Motor and cognitive deficits in apolipoprotein E-deficient mice after closed head injury

Y. Chen, L. Lomnitski, D. M. Michaelson, E. Shohami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

195 Scopus citations

Abstract

Previous studies suggest that traumatic brain injury is associated with increased risk factor for developing Alzheimer's disease. Furthermore, the extent of the risk seems to be most pronounced in Alzheimer's disease patients who carry the ε4 allele of apolipoprotein E, suggesting a connection between susceptibility to head trauma and the apolipoprotein E genotype. Apolipoprotein E-deficient mice provide a useful model for investigating the role of this lipoprotein in neuronal maintenance and repair. In the present study apolipoprotein E-deficient mice and a closed head injury experimental paradigm were used to examine the role of apolipoprotein E in brain susceptibility to head trauma and in neuronal repair. Apolipoprotein E-deficient mice were assessed up to 40 days after closed head injury for neurological and cognitive functions, as well as for histopathological changes in the hippocampus. A neurological severity score used for clinical assessment revealed more severe motor and behavioural deficits in the apolipoprotein E-deficient mice than in the controls; the impairment persisting for at least 40 days after injury. Performance in the Morris water maze, which tests spatial memory, showed a marked learning deficit of the apolipoprotein E-deficient mice when compared with injured controls, which was apparent for at least 40 days. At this time, histopathological examination revealed overt neuronal cell death bilaterally in the hippocampus of the injured apolipoprotein E-deficient mice. The finding that apolipoprotein E-deficient mice exhibit an impaired ability to recover from closed head injury suggests that apolipoprotein E plays an important role in neuronal repair following injury and highlights the applicability of this mouse model to the study of the cellular and molecular mechanisms involved.

Original languageEnglish
Pages (from-to)1255-1262
Number of pages8
JournalNeuroscience
Volume80
Issue number4
DOIs
StatePublished - 11 Aug 1997

Keywords

  • Alzheimer's disease
  • Apolipoprotein E
  • Closed head injury
  • Histopathology
  • Memory
  • Motor function

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