Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection

Rachel Karlnoski, Donna Wilcock, Chad Dickey, Victoria Ronan, Marcia N. Gordon, Wenru Zhang, Dave Morgan, Giulio Taglialatela

Research output: Contribution to journalArticlepeer-review

31 Scopus citations

Abstract

Aβ-induced neurodegeneration is limited in APP and APP + PS1 transgenic mice. In middle-aged APP + PS1 transgenic mice, we found significantly increased Bcl-2 expression. The increase in Bcl-2 is restricted to amyloid-containing brain regions and is not found at young ages, suggesting that Aβ deposition is the stimulus for increased Bcl-2. Western blot results were confirmed with immunohistochemistry and qRT-PCR. In addition, we found that APP transgenic mice were protected from neurotoxicity caused by an injection of bak BH3 fusion peptides, known to induce apoptosis by antagonizing bcl protein activity. Nissl and fluorojade-stained slides showed that the active bak BH3 peptide caused substantial neuronal loss in the dentate gyrus and CA3 regions of nontransgenic, but not APP mice. The inactive mutant bak BH3 peptide did not cause degeneration in any mice. These data demonstrate that the increased Bcl-2 expression in brain regions containing Aβ deposits is associated with neuroprotection.

Original languageEnglish
Pages (from-to)179-188
Number of pages10
JournalNeurobiology of Disease
Volume25
Issue number1
DOIs
StatePublished - Jan 2007

Bibliographical note

Funding Information:
This work was supported by AG 15490 and 18478 to DM and MNG and by a Sealy Endowed Fund for Biomedical Research Development Grant to GT. DM also receives salary support from AG25711 and NS 48355. RK is the Thorne Scholar for Alzheimer’s Research. DW is the Benjamin fellow for Alzheimer’s Research. We thank Karen Hsiao Ashe and Karen Duff for early access to the APP and APP + PS1 mice.

Keywords

  • APP + PS1 transgenic mice
  • Alzheimer's disease
  • Apoptosis
  • Bax
  • Neurotoxicity

ASJC Scopus subject areas

  • Neurology

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