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Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress
The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discov...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770249/ https://www.ncbi.nlm.nih.gov/pubmed/31505850 http://dx.doi.org/10.3390/nu11092161 |
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author | Ano, Yasuhisa Kita, Masahiro Kitaoka, Shiho Furuyashiki, Tomoyuki |
author_facet | Ano, Yasuhisa Kita, Masahiro Kitaoka, Shiho Furuyashiki, Tomoyuki |
author_sort | Ano, Yasuhisa |
collection | PubMed |
description | The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine–histidine (LH) dipeptide suppressed activation of primary microglia. The effects of LH dipeptide orally administered were measured using tail suspension test (TST) in mice injected with lipopolysaccharide and social interaction test in mice received social defeat stress. LH dipeptide reduced pro-inflammatory cytokines upon stimulation in microglia. Orally administered LH dipeptide was delivered to the brain and suppressed the production of pro-inflammatory cytokines in the brain and concomitant depression-like behavior in the TST. Moreover, oral administration of LH dipeptide suppressed the induction of depression- and anxiety-like behaviors induced by repeated social defeat stress. These results indicate that LH dipeptide suppressed the activation of microglia and ameliorated depression-associated emotional disturbances. Further, we found that LH dipeptide was abundant in various fermented products. Together with previous epidemiological reports that daily intake of these fermented foods is negatively associated with the incidence of psychiatric diseases, our findings suggest that food rich in LH dipeptide may improve mental health. |
format | Online Article Text |
id | pubmed-6770249 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67702492019-10-30 Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress Ano, Yasuhisa Kita, Masahiro Kitaoka, Shiho Furuyashiki, Tomoyuki Nutrients Article The number of patients with mental illnesses is rapidly increasing, and daily lifestyle is closely associated with the development of symptoms. It is suggested that inflammatory molecules derived from microglia play crucial roles for the pathophysiology of depression. In the present study, we discovered that leucine–histidine (LH) dipeptide suppressed activation of primary microglia. The effects of LH dipeptide orally administered were measured using tail suspension test (TST) in mice injected with lipopolysaccharide and social interaction test in mice received social defeat stress. LH dipeptide reduced pro-inflammatory cytokines upon stimulation in microglia. Orally administered LH dipeptide was delivered to the brain and suppressed the production of pro-inflammatory cytokines in the brain and concomitant depression-like behavior in the TST. Moreover, oral administration of LH dipeptide suppressed the induction of depression- and anxiety-like behaviors induced by repeated social defeat stress. These results indicate that LH dipeptide suppressed the activation of microglia and ameliorated depression-associated emotional disturbances. Further, we found that LH dipeptide was abundant in various fermented products. Together with previous epidemiological reports that daily intake of these fermented foods is negatively associated with the incidence of psychiatric diseases, our findings suggest that food rich in LH dipeptide may improve mental health. MDPI 2019-09-09 /pmc/articles/PMC6770249/ /pubmed/31505850 http://dx.doi.org/10.3390/nu11092161 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ano, Yasuhisa Kita, Masahiro Kitaoka, Shiho Furuyashiki, Tomoyuki Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title | Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title_full | Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title_fullStr | Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title_full_unstemmed | Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title_short | Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress |
title_sort | leucine–histidine dipeptide attenuates microglial activation and emotional disturbances induced by brain inflammation and repeated social defeat stress |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770249/ https://www.ncbi.nlm.nih.gov/pubmed/31505850 http://dx.doi.org/10.3390/nu11092161 |
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