Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ano, Yasuhisa, Kita, Masahiro, Kitaoka, Shiho, Furuyashiki, Tomoyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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
_version_ 1783455427743186944
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
work_keys_str_mv AT anoyasuhisa leucinehistidinedipeptideattenuatesmicroglialactivationandemotionaldisturbancesinducedbybraininflammationandrepeatedsocialdefeatstress
AT kitamasahiro leucinehistidinedipeptideattenuatesmicroglialactivationandemotionaldisturbancesinducedbybraininflammationandrepeatedsocialdefeatstress
AT kitaokashiho leucinehistidinedipeptideattenuatesmicroglialactivationandemotionaldisturbancesinducedbybraininflammationandrepeatedsocialdefeatstress
AT furuyashikitomoyuki leucinehistidinedipeptideattenuatesmicroglialactivationandemotionaldisturbancesinducedbybraininflammationandrepeatedsocialdefeatstress