Journal of Neural Transmission

, Volume 111, Issue 4, pp 523–536

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

  • I. Blasko
  • R. Beer
  • M. Bigl
  • J. Apelt
  • G. Franz
  • D. Rudzki
  • G. Ransmayr
  • A. Kampfl
  • R. Schliebs
Article

DOI: 10.1007/s00702-003-0095-6

Cite this article as:
Blasko, I., Beer, R., Bigl, M. et al. J Neural Transm (2004) 111: 523. doi:10.1007/s00702-003-0095-6

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.

Keywords: Brain trauma, Alzheimer’s disease, BACE-1, BACE-1 activity, AβPP 

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Copyright information

© Springer-Verlag/Wien 2004

Authors and Affiliations

  • I. Blasko
    • 1
    • 2
  • R. Beer
    • 2
  • M. Bigl
    • 4
  • J. Apelt
    • 3
  • G. Franz
    • 2
  • D. Rudzki
    • 1
  • G. Ransmayr
    • 2
  • A. Kampfl
    • 2
  • R. Schliebs
    • 3
  1. 1.Department of PsychiatryUniversity Hospital of InnsbruckInnsbruckAustria
  2. 2.Department of NeurologyUniversity Hospital of InnsbruckInnsbruckAustria
  3. 3.Paul Flechsig Institute of Brain Research, University of LeipzigGermany
  4. 4.Institute of Biochemistry, Medical Faculty, University of LeipzigGermany

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