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Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease

Biscaro, Barbara; Lindvall, Olle LU ; Tesco, Giuseppina; Ekdahl Clementson, Christine LU and Nitsch, Roger M. (2012) In Neurodegenerative Diseases 9(4). p.187-198
Abstract
Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of microglia on neurogenesis in brains with A beta pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). Results: Minocycline increased the survival of new dentate granule cells in APP/PS1 mice... (More)
Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of microglia on neurogenesis in brains with A beta pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). Results: Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of A beta and A beta-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice. Conclusions: These results suggest a role for microglia in A beta-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of A beta pathology. Copyright (C) 2012 S. Karger AG, Basel (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Microglia, Minocycline, Amyloid precursor protein, Presenilin, beta-Amyloid, Inflammation
in
Neurodegenerative Diseases
volume
9
issue
4
pages
187 - 198
publisher
Karger
external identifiers
  • wos:000303862100004
  • scopus:84862088615
ISSN
1660-2862
DOI
10.1159/000330363
language
English
LU publication?
yes
id
d3790da7-c9d8-4e4a-9cf1-87f2b10f0432 (old id 2826902)
date added to LUP
2012-07-03 10:27:17
date last changed
2017-11-19 03:21:55
@article{d3790da7-c9d8-4e4a-9cf1-87f2b10f0432,
  abstract     = {Background: Activated microglia with macrophage-like functions invade and surround beta-amyloid (A beta) plaques in Alzheimer's disease (AD), possibly contributing to the turnover of A beta, but they can also secrete proinflammatory factors that may be involved in the pathogenesis of AD. Microglia are known to modulate adult hippocampal neurogenesis. Objectives/Methods: To determine the role of microglia on neurogenesis in brains with A beta pathology, we inhibited microglial activation with the tetracycline derivative minocycline in doubly transgenic mice expressing mutant human amyloid precursor protein (APP) and mutant human presenilin-1 (PS1). Results: Minocycline increased the survival of new dentate granule cells in APP/PS1 mice indicated by more BrdU+/NeuN+ cells as compared to vehicle-treated transgenic littermates, accompanied by improved behavioral performance in a hippocampus-dependent learning task. Both brain levels of A beta and A beta-related morphological deficits in the new neurons labeled with GFP-expressing retrovirus were unaffected in minocycline-treated mice. Conclusions: These results suggest a role for microglia in A beta-related functional deficits and in suppressing the survival of new neurons, and show that modulation of microglial function with minocycline can protect hippocampal neurogenesis in the presence of A beta pathology. Copyright (C) 2012 S. Karger AG, Basel},
  author       = {Biscaro, Barbara and Lindvall, Olle and Tesco, Giuseppina and Ekdahl Clementson, Christine and Nitsch, Roger M.},
  issn         = {1660-2862},
  keyword      = {Microglia,Minocycline,Amyloid precursor protein,Presenilin,beta-Amyloid,Inflammation},
  language     = {eng},
  number       = {4},
  pages        = {187--198},
  publisher    = {Karger},
  series       = {Neurodegenerative Diseases},
  title        = {Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease},
  url          = {http://dx.doi.org/10.1159/000330363},
  volume       = {9},
  year         = {2012},
}