Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein

Makoto Masumura, Ryuji Hata, Isao Nishimura, Taichi Uetsuki, Tohru Sawada, Kazuaki Yoshikawa

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

To elucidate the mechanism of neuronal death in Alzheimer's disease, we investigated the effects of overexpression of wild-type Alzheimer amyloid precursor protein (APP) on neuronal cells and glial cells in vivo. When an APP695-expressing adenovirus was injected into the dorsal hippocampal region, a number of neurons in remote areas were positively stained with anti-APP monoclonal antibody, and underwent severe degeneration from 3 to 7 days after viral inoculation. Most degenerating neurons were immunopositive with both APP and activated caspase-3, but some neurons that expressed activated caspase-3 were not expressing APP from 7 to 14 days after virus injection. In the neighborhood of the degenerating neurons, activated microglia/macrophages, which were identified by the phenotypic marker C3bi receptor (CD11b/c; OX-42), were observed, and some of them appeared to phagocytose the caspase-3-immunopositive degenerating neurons. In addition to microglia/macrophages, infiltrating leukocytes expressing CD45 or CD4 were also detected. These results suggest that the increased accumulation of APP induced not only caspase-3-mediated death machinery, but also inflammatory responses including microglial activation. These inflammatory responses might cause further neurodegeneration through the alternative pathway that might activate the caspase-3-mediated death machinery without APP expression. (C) 2000 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)219-227
Number of pages9
JournalMolecular Brain Research
Volume80
Issue number2
DOIs
Publication statusPublished - 15-09-2000

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Amyloid beta-Protein Precursor
Adenoviridae
Caspase 3
Hippocampus
Neurons
Microglia
Macrophages
Complement C3b
Phagocytosis
Neuroglia
Alzheimer Disease
Leukocytes
Monoclonal Antibodies
Viruses
Injections

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

Masumura, Makoto ; Hata, Ryuji ; Nishimura, Isao ; Uetsuki, Taichi ; Sawada, Tohru ; Yoshikawa, Kazuaki. / Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein. In: Molecular Brain Research. 2000 ; Vol. 80, No. 2. pp. 219-227.
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Caspase-3 activation and inflammatory responses in rat hippocampus inoculated with a recombinant adenovirus expressing the Alzheimer amyloid precursor protein. / Masumura, Makoto; Hata, Ryuji; Nishimura, Isao; Uetsuki, Taichi; Sawada, Tohru; Yoshikawa, Kazuaki.

In: Molecular Brain Research, Vol. 80, No. 2, 15.09.2000, p. 219-227.

Research output: Contribution to journalArticle

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