Inhibition of Microglial Activation Protects Hippocampal Neurogenesis and Improves Cognitive Deficits in a Transgenic Mouse Model for Alzheimer's Disease
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2826902
- author
- Biscaro, Barbara ; Lindvall, Olle LU ; Tesco, Giuseppina ; Ekdahl Clementson, Christine LU and Nitsch, Roger M.
- organization
- publishing date
- 2012
- 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
- pmid:22584394
- 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
- 2016-04-01 11:05:50
- date last changed
- 2022-05-13 22:57:54
@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}}, keywords = {{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}}, doi = {{10.1159/000330363}}, volume = {{9}}, year = {{2012}}, }