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Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome
Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of t...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736620/ https://www.ncbi.nlm.nih.gov/pubmed/33027640 http://dx.doi.org/10.1016/j.neuron.2020.09.010 |
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author | Pinto, Bruno Morelli, Giovanni Rastogi, Mohit Savardi, Annalisa Fumagalli, Amos Petretto, Andrea Bartolucci, Martina Varea, Emilio Catelani, Tiziano Contestabile, Andrea Perlini, Laura E. Cancedda, Laura |
author_facet | Pinto, Bruno Morelli, Giovanni Rastogi, Mohit Savardi, Annalisa Fumagalli, Amos Petretto, Andrea Bartolucci, Martina Varea, Emilio Catelani, Tiziano Contestabile, Andrea Perlini, Laura E. Cancedda, Laura |
author_sort | Pinto, Bruno |
collection | PubMed |
description | Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals. |
format | Online Article Text |
id | pubmed-7736620 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-77366202020-12-18 Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome Pinto, Bruno Morelli, Giovanni Rastogi, Mohit Savardi, Annalisa Fumagalli, Amos Petretto, Andrea Bartolucci, Martina Varea, Emilio Catelani, Tiziano Contestabile, Andrea Perlini, Laura E. Cancedda, Laura Neuron Article Microglia are brain-resident immune cells and regulate mechanisms essential for cognitive functions. Down syndrome (DS), the most frequent cause of genetic intellectual disability, is caused by a supernumerary chromosome 21, containing also genes related to the immune system. In the hippocampus of the Dp(16) mouse model of DS and DS individuals, we found activated microglia, as assessed by their morphology; activation markers; and, for DS mice, electrophysiological profile. Accordingly, we found increased pro-inflammatory cytokine levels and altered interferon signaling in Dp(16) hippocampi. DS mice also showed decreased spine density and activity of hippocampal neurons and hippocampus-dependent cognitive behavioral deficits. Depletion of defective microglia or treatment with a commonly used anti-inflammatory drug rescued the neuronal spine and activity impairments and cognitive deficits in juvenile Dp(16) mice. Our results suggest an involvement of microglia in Dp(16)-mouse cognitive deficits and identify a new potential therapeutic approach for cognitive disabilities in DS individuals. Cell Press 2020-12-09 /pmc/articles/PMC7736620/ /pubmed/33027640 http://dx.doi.org/10.1016/j.neuron.2020.09.010 Text en © 2020 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Pinto, Bruno Morelli, Giovanni Rastogi, Mohit Savardi, Annalisa Fumagalli, Amos Petretto, Andrea Bartolucci, Martina Varea, Emilio Catelani, Tiziano Contestabile, Andrea Perlini, Laura E. Cancedda, Laura Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title | Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title_full | Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title_fullStr | Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title_full_unstemmed | Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title_short | Rescuing Over-activated Microglia Restores Cognitive Performance in Juvenile Animals of the Dp(16) Mouse Model of Down Syndrome |
title_sort | rescuing over-activated microglia restores cognitive performance in juvenile animals of the dp(16) mouse model of down syndrome |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7736620/ https://www.ncbi.nlm.nih.gov/pubmed/33027640 http://dx.doi.org/10.1016/j.neuron.2020.09.010 |
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