Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer’s disease β-secretase (BACE-1) (original) (raw)

Summary.

Traumatic brain injury (TBI) is a risk factor for the development of Alzheimer’s disease (AD). After a traumatic brain injury depositions of amyloid beta (Aβ) in the brain parenchyma were found. In this study we investigated the expression pattern of β-secretase (BACE-1) in ipsi- or contralateral hippocampus and cortex following controlled cortical TBI in rats. BACE-1 mRNA levels, estimated by real time RT-PCR, were elevated 24 h post injury, and persisting up to 72 h, in the ipsi- and contralateral hippocampus and cerebral cortex as compared to the sham-treated animals (p<0.01). The TBI-induced changes in BACE-1 mRNA are due to enhanced hippocampal and cortical expression of BACE-1 mRNA in neurons and reactive astrocytes as revealed by in situ hybridization. The alterations in hippocampal BACE-1 mRNA levels are accompanied by corresponding increases in BACE-1 protein levels in ipsi- and contralateral hippocampus and ipsilateral cortex as demonstrated by Western blot analysis. In contrast, in the contralateral cortex only a weak increase of traumatically induced BACE-1 protein production was found. The activity of BACE-1 as measured by the formation of the cleavage product of amyloid beta precursor protein, transiently increased up to 48 h after injury, but returned to basal level 7 days post injury. This study demonstrates that the β-secretase is stimulated following TBI and may suggest a mechanism for the temporal increase of Aβ levels observed in patients with brain trauma.

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Authors and Affiliations

  1. Department of Psychiatry, University Hospital of Innsbruck, Innsbruck, Austria
    I. Blasko & D. Rudzki
  2. Department of Neurology, University Hospital of Innsbruck, Innsbruck, Austria
    I. Blasko, R. Beer, G. Franz, G. Ransmayr & A. Kampfl
  3. Paul Flechsig Institute of Brain Research, University of Leipzig, Germany
    J. Apelt & R. Schliebs
  4. Institute of Biochemistry, Medical Faculty, University of Leipzig, Germany
    M. Bigl

Authors

  1. I. Blasko
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  2. R. Beer
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  3. M. Bigl
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  4. J. Apelt
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  5. G. Franz
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  6. D. Rudzki
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  7. G. Ransmayr
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  8. A. Kampfl
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  9. R. Schliebs
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Blasko, I., Beer, R., Bigl, M. et al. Experimental traumatic brain injury in rats stimulates the expression, production and activity of Alzheimer’s disease β-secretase (BACE-1).J Neural Transm 111, 523–536 (2004). https://doi.org/10.1007/s00702-003-0095-6

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