Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection.
Abeta-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 Abeta 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 Abeta deposits is associated with neuroprotection.
Karlnoski
Rachel
R
Alzheimer's Research Laboratory, Department of Molecular Pharmacology and Physiology, University of South Florida, 12901 Bruce B. Downs Boulevard, MDC Box 9, Tampa, FL 33612, USA.
Wilcock
Donna
D
Dickey
Chad
C
Ronan
Victoria
V
Gordon
Marcia N
MN
Zhang
Wenru
W
Morgan
Dave
D
Taglialatela
Giulio
G
D016229:Amyloid beta-Peptides / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D051023:BH3 Interacting Domain Death Agonist Protein / Q000494:pharmacology; D015153:Blotting, Western; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology; D053764:Presenilin-1 / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013788:Thalamus / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D016229:Amyloid beta-Peptides; D051023:BH3 Interacting Domain Death Agonist Protein; D053764:Presenilin-1; D019253:Proto-Oncogene Proteins c-bcl-2