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 journalArticle

22 Citations (Scopus)

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

Fingerprint

Transgenic Mice
Up-Regulation
Dentate Gyrus
Brain
Amyloid
Western Blotting
Immunohistochemistry
Apoptosis
Polymerase Chain Reaction
Injections
Bax protein (53-86)
Neuroprotection
Proteins

Keywords

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

ASJC Scopus subject areas

  • Neurology

Cite this

Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection. / Karlnoski, Rachel; Wilcock, Donna; Dickey, Chad; Ronan, Victoria; Gordon, Marcia N.; Zhang, Wenru; Morgan, Dave; Taglialatela, Giulio.

In: Neurobiology of Disease, Vol. 25, No. 1, 01.2007, p. 179-188.

Research output: Contribution to journalArticle

Karlnoski, R, Wilcock, D, Dickey, C, Ronan, V, Gordon, MN, Zhang, W, Morgan, D & Taglialatela, G 2007, 'Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection', Neurobiology of Disease, vol. 25, no. 1, pp. 179-188. https://doi.org/10.1016/j.nbd.2006.09.007
Karlnoski R, Wilcock D, Dickey C, Ronan V, Gordon MN, Zhang W et al. Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection. Neurobiology of Disease. 2007 Jan;25(1):179-188. https://doi.org/10.1016/j.nbd.2006.09.007
Karlnoski, Rachel ; Wilcock, Donna ; Dickey, Chad ; Ronan, Victoria ; Gordon, Marcia N. ; Zhang, Wenru ; Morgan, Dave ; Taglialatela, Giulio. / Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection. In: Neurobiology of Disease. 2007 ; Vol. 25, No. 1. pp. 179-188.
@article{10b9405999b6472b925541b8dc31e02a,
title = "Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection",
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.",
keywords = "Aβ, Alzheimer's disease, Apoptosis, APP + PS1 transgenic mice, Bax, Neurotoxicity",
author = "Rachel Karlnoski and Donna Wilcock and Chad Dickey and Victoria Ronan and Gordon, {Marcia N.} and Wenru Zhang and Dave Morgan and Giulio Taglialatela",
year = "2007",
month = "1",
doi = "10.1016/j.nbd.2006.09.007",
language = "English (US)",
volume = "25",
pages = "179--188",
journal = "Neurobiology of Disease",
issn = "0969-9961",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Up-regulation of Bcl-2 in APP transgenic mice is associated with neuroprotection

AU - Karlnoski, Rachel

AU - Wilcock, Donna

AU - Dickey, Chad

AU - Ronan, Victoria

AU - Gordon, Marcia N.

AU - Zhang, Wenru

AU - Morgan, Dave

AU - Taglialatela, Giulio

PY - 2007/1

Y1 - 2007/1

N2 - 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.

AB - 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.

KW - Aβ

KW - Alzheimer's disease

KW - Apoptosis

KW - APP + PS1 transgenic mice

KW - Bax

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=33751098042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751098042&partnerID=8YFLogxK

U2 - 10.1016/j.nbd.2006.09.007

DO - 10.1016/j.nbd.2006.09.007

M3 - Article

VL - 25

SP - 179

EP - 188

JO - Neurobiology of Disease

JF - Neurobiology of Disease

SN - 0969-9961

IS - 1

ER -