Cargando…
Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events
Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits comp...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657487/ https://www.ncbi.nlm.nih.gov/pubmed/36361832 http://dx.doi.org/10.3390/ijms232113052 |
_version_ | 1784829707286478848 |
---|---|
author | Sah, Anupam Rooney, Sinead Kharitonova, Maria Sartori, Simone B. Wolf, Susanne A. Singewald, Nicolas |
author_facet | Sah, Anupam Rooney, Sinead Kharitonova, Maria Sartori, Simone B. Wolf, Susanne A. Singewald, Nicolas |
author_sort | Sah, Anupam |
collection | PubMed |
description | Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, “positive environmental stimuli”, which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety. |
format | Online Article Text |
id | pubmed-9657487 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-96574872022-11-15 Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events Sah, Anupam Rooney, Sinead Kharitonova, Maria Sartori, Simone B. Wolf, Susanne A. Singewald, Nicolas Int J Mol Sci Article Neuroinflammation is discussed to play a role in specific subgroups of different psychiatric disorders, including anxiety disorders. We have previously shown that a mouse model of trait anxiety (HAB) displays enhanced microglial density and phagocytic activity in key regions of anxiety circuits compared to normal-anxiety controls (NAB). Using minocycline, we provided causal evidence that reducing microglial activation within the dentate gyrus (DG) attenuated enhanced anxiety in HABs. Besides pharmacological intervention, “positive environmental stimuli”, which have the advantage of exerting no side-effects, have been shown to modulate inflammation-related markers in human beings. Therefore, we now investigated whether environmental enrichment (EE) would be sufficient to modulate upregulated neuroinflammation in high-anxiety HABs. We show for the first time that EE can indeed attenuate enhanced trait anxiety, even when presented as late as adulthood. We further found that EE-induced anxiolysis was associated with the attenuation of enhanced microglial density (using Iba-1 as the marker) in the DG and medial prefrontal cortex. Additionally, EE reduced Iba1 + CD68+ microglia density within the anterior DG. Hence, the successful attenuation of trait anxiety by EE was associated in part with the normalization of neuro-inflammatory imbalances. These results suggest that pharmacological and/or positive behavioral therapies triggering microglia-targeted anti-inflammatory effects could be promising as novel alternatives or complimentary anxiolytic therapeutic approaches in specific subgroups of individuals predisposed to trait anxiety. MDPI 2022-10-27 /pmc/articles/PMC9657487/ /pubmed/36361832 http://dx.doi.org/10.3390/ijms232113052 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Sah, Anupam Rooney, Sinead Kharitonova, Maria Sartori, Simone B. Wolf, Susanne A. Singewald, Nicolas Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title | Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title_full | Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title_fullStr | Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title_full_unstemmed | Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title_short | Enriched Environment Attenuates Enhanced Trait Anxiety in Association with Normalization of Aberrant Neuro-Inflammatory Events |
title_sort | enriched environment attenuates enhanced trait anxiety in association with normalization of aberrant neuro-inflammatory events |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9657487/ https://www.ncbi.nlm.nih.gov/pubmed/36361832 http://dx.doi.org/10.3390/ijms232113052 |
work_keys_str_mv | AT sahanupam enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents AT rooneysinead enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents AT kharitonovamaria enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents AT sartorisimoneb enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents AT wolfsusannea enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents AT singewaldnicolas enrichedenvironmentattenuatesenhancedtraitanxietyinassociationwithnormalizationofaberrantneuroinflammatoryevents |