scholarly journals Leucine–Histidine Dipeptide Attenuates Microglial Activation and Emotional Disturbances Induced by Brain Inflammation and Repeated Social Defeat Stress

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2161 ◽  
Author(s):  
Yasuhisa Ano ◽  
Masahiro Kita ◽  
Shiho Kitaoka ◽  
Tomoyuki Furuyashiki
Keyword(s):  
Inflammatory Cytokines ◽  
Social Defeat ◽  
Emotional Disturbances ◽  
Mental Illnesses ◽  
Brain Inflammation ◽  
Fermented Foods ◽  
Social Defeat Stress ◽  
Number Of Patients ◽  
The Brain ◽  
Pro Inflammatory Cytokines

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.

scholarly journals Attenuation of Inflammation and Leptin Resistance by Pyrogallol-Phloroglucinol-6,6-Bieckol on in the Brain of Obese Animal Models

Nutrients ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 2773 ◽  
Author(s):  
Myeongjoo Son ◽  
Seyeon Oh ◽  
Junwon Choi ◽  
Ji Tae Jang ◽  
Chang Hu Choi ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Cytokines ◽  
Brain Inflammation ◽  
Leptin Resistance ◽  
Diet Induced Obesity ◽  
Leptin Sensitivity ◽  
M1 Polarization ◽  
Activated Macrophage ◽  
The Brain ◽  
Pro Inflammatory Cytokines

Obesity induces inflammation both in the adipose tissue and the brain. Activated macrophage infiltration, polarization of macrophages to a more inflammatory type (M1), and increased levels of pro-inflammatory cytokines are related to brain inflammation, which induces leptin resistance in the brain. Pyrogallol-phloroglucinol-6,6-bieckol (PPB), a compound from Ecklonia cava, has anti-inflammatory effects. In this study, we evaluated the effects of PPB effect M1 polarization and inflammation and its ability to restore the effects of leptin, such as a decrease in appetite and body weight. We administered PPB to diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice, evaluated macrophage activation, polarization, and changes of inflammatory cytokine level in adipose tissue and brain, and determined the effect of PPB on leptin resistance or leptin sensitivity in the brain. The levels of activated macrophage marker, M1/M2, and pro-inflammatory cytokines were increased in the adipose tissue and brain of DIO and ob/ob mice than control. TLR4 expression, endoplasmic reticulum (ER) stress, and NF-κB expression in the brain of DIO and ob/ob mice were also increased; this increase was related to the upregulation of SOCS3 and decreased phosphorylated STAT3, which decreased leptin sensitivity in the brain. PPB decreased inflammation in the brain, restored leptin sensitivity, and decreased food intake and weight gain in both DIO and ob/ob mice.

scholarly journals Interaction Between Social Defeat Stress and Chronic Ethanol Exposure on Behaviors During Ethanol Withdrawal and Pro-Inflammatory Cytokines in Mice

2021 ◽  
Vol 2 ◽  
pp. 1-11
Author(s):  
Gessynger Morais-Silva ◽  
Pedro B. Portilho ◽  
Juliana Fernandes-Santos ◽  
Rafaella M. Queiroz ◽  
Simone R. Deconte ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Social Defeat ◽  
Ethanol Exposure ◽  
Ethanol Withdrawal ◽  
Chronic Ethanol ◽  
Social Defeat Stress ◽  
Chronic Ethanol Exposure ◽  
Pro Inflammatory Cytokines

scholarly journals Th17 Cells Interactions with the Brain Endothelium in Vitro

2017 ◽  
Author(s):  
Dagmara Weronika Wojkowska ◽  
Piotr Szpakowski ◽  
Andrzej Glabinski
Keyword(s):  
Inflammatory Cytokines ◽  
Th17 Cells ◽  
Inflammatory Cell ◽  
Early Stage ◽  
Brain Inflammation ◽  
Brain Endothelium ◽  
The Central Nervous System ◽  
The Brain ◽  
Pro Inflammatory Cytokines

The nature of the interaction between Th17 cells and the blood-brain barrier (BBB) is critical for the development of autoimmune inflammation in the central nervous system (CNS). TNF-a or IL-17 stimulation is known to enhance the adherence of Th17 cells to the brain endothelium. The brain endothelial cells (bEnd.3) express VCAM-1, the receptor responsible for inflammatory cell adhesion, which binds VLA-4 on migrating effector lymphocytes at the early stage of brain inflammation. The present study examines the effect of the pro-inflammatory cytokines TNF-a and IL-17 on the adherence of Th17 cells to bEnd.3 The bEnd.3 cells were found to increase production of CCL2 and CXCL1 after stimulation by pro-inflammatory cytokines, while CCL2, CCL5, CCL20 and IL17 induced Th17 cell migration through a bEnd.3 monolayer. This interaction between Th17 cells and the brain endothelium appears to be mediated by VCAM-1 and some chemotactic cytokines. This observation may suggest potential therapeutic targets for the prevention of autoimmune neuroinflammation development in the CNS.

scholarly journals Hop Bitter Acids Increase Hippocampal Dopaminergic Activity in a Mouse Model of Social Defeat Stress

2020 ◽  
Vol 21 (24) ◽  
pp. 9612
Author(s):  
Yasuhisa Ano ◽  
Shiho Kitaoka ◽  
Rena Ohya ◽  
Keiji Kondo ◽  
Tomoyuki Furuyashiki
Keyword(s):  
Mouse Model ◽  
Chronic Administration ◽  
Social Defeat ◽  
Underlying Mechanism ◽  
Mental Illnesses ◽  
Social Avoidance ◽  
Social Defeat Stress ◽  
Dopaminergic Activity ◽  
Healthy Older Adults ◽  
Bitter Acids

As daily lifestyle is closely associated with mental illnesses, diet-based preventive approaches are receiving attention. Supplementation with hop bitter acids such as iso-α-acids (IAA) and mature hop bitter acids (MHBA) improves mood states in healthy older adults. However, the underlying mechanism remains unknown. Since acute oral consumption with IAA increases dopamine levels in hippocampus and improves memory impairment via vagal nerve activation, here we investigated the effects of chronic administration of hop bitter acids on the dopaminergic activity associated with emotional disturbance in a mouse model of repeated social defeat stress (R-SDS). Chronic administration of IAA and MHBA significantly increased dopaminergic activity based on the dopamine metabolite to dopamine ratio in the hippocampus and medial prefrontal cortex following R-SDS. Hippocampal dopaminergic activity was inversely correlated with the level of R-SDS-induced social avoidance with or without IAA administration. Therefore, chronic treatment with hop bitter acids enhances stress resilience-related hippocampal dopaminergic activity.

scholarly journals Roles of multiple lipid mediators in stress and depression

2019 ◽  
Vol 31 (9) ◽  
pp. 579-587 ◽  
Author(s):  
Tomoyuki Furuyashiki ◽  
Satoshi Akiyama ◽  
Shiho Kitaoka
Keyword(s):  
Chronic Stress ◽  
Social Defeat ◽  
Lipid Mediators ◽  
Mental Illnesses ◽  
Lipid Mediator ◽  
Receptor Subtype ◽  
Social Defeat Stress ◽  
Beneficial Effects ◽  
Prostaglandin Synthase ◽  
Depressive Patients

AbstractProlonged or excessive stress may induce emotional and cognitive disturbances, and is a risk factor for mental illnesses. Using rodent chronic stress models of depression, roles of multiple lipid mediators related to inflammation have been revealed in chronic stress-induced emotional alterations. Prostaglandin (PG) E2, an arachidonic acid (AA)-derived lipid mediator, and its receptor subtype EP1 mediate depression-like behavior induced by repeated social defeat stress through attenuating prefrontal dopaminergic activity. Repeated social defeat stress activates microglia through innate immune receptors, and induces PGE2 synthesis through cyclooxygenase-1, a prostaglandin synthase enriched in microglia. PGD2, another AA-derived lipid mediator, has been implicated in depression induced by chronic stress, although either pro-depressive or anti-depressive actions have been reported. Chronic stress up-regulates hippocampal expression of 5-lipoxygenase, hence synthesis of cysteinyl leukotrienes, thereby inducing depression through their receptors. Consistent with beneficial effects of n-3 fatty acids in the diet of depressive patients, resolvins—a novel class of pro-resolving lipid mediators—in the brain attenuate neuroinflammation-associated depression. These findings in animal models of depression offer lipid mediators and related molecules as novel therapeutic targets for treating depression. To translate these findings into clinics, translational biomarkers to visualize lipid mediator profiles in depressive patients need to be established.

Social defeat stress affects resident’s clock gene and bdnf expression in the brain

Stress ◽  
2020 ◽  
pp. 1-7
Author(s):  
Simona Moravcová ◽  
Kateřina Červená ◽  
Hana Míková ◽  
Dominika Pačesová ◽  
Gergely Pallag ◽  
...  
Keyword(s):  
Clock Gene ◽  
Social Defeat ◽  
Social Defeat Stress ◽  
Bdnf Expression ◽  
The Brain

scholarly journals Electroacupuncture improves repeated social defeat stress-elicited social avoidance and anxiety-like behaviors by reducing Lipocalin-2 in the hippocampus

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yi-Hung Chen ◽  
Sheng-Yun Xie ◽  
Chao-Wei Chen ◽  
Dah-Yuu Lu
Keyword(s):  
Monoamine Oxidase ◽  
Social Defeat ◽  
Monoamine Oxidase A ◽  
Sequencing Analysis ◽  
Social Avoidance ◽  
Lipocalin 2 ◽  
Social Defeat Stress ◽  
Astrocyte Activation ◽  
Related Disorder ◽  
The Brain

Abstract Background Post-traumatic stress disorder (PTSD) is a trauma-related disorder that is associated with pro-inflammatory activation and neurobiological impairments in the brain and leads to a series of affective-like behaviors. Electroacupuncture (EA) has been proposed as a clinically useful therapy for several brain diseases. However, the potential role of EA treatment in PTSD and its molecular and cellular mechanisms has rarely been investigated. Methods We used an established preclinical social defeat stress mouse model to study whether EA treatment modulates PTSD-like symptoms and understand its underlying mechanisms. To this end, male C57BL/6 mice were subjected to repeated social defeat stress (RSDS) for 6 consecutive days to induce symptoms of PTSD and treated with EA at Baihui (GV 20) and Dazhui (GV 14) acupoints. Results The stimulation of EA, but not needle insertion at Baihui (GV 20) and Dazhui (GV 14) acupoints effectively improved PTSD-like behaviors such as, social avoidance and anxiety-like behaviors. However, EA stimulation at the bilateral Tianzong (SI11) acupoints did not affect the PTSD-like behaviors obtained by RSDS. EA stimulation also markedly inhibited astrocyte activation in both the dorsal and ventral hippocampi of RSDS-treated mice. Using next-generation sequencing analysis, our results showed that EA stimulation attenuated RSDS-enhanced lipocalin 2 expression in the hippocampus. Importantly, using double-staining immunofluorescence, we observed that the increased lipocalin 2 expression in astrocytes by RSDS was also reduced by EA stimulation. In addition, intracerebroventricular injection of mouse recombinant lipocalin 2 protein in the lateral ventricles provoked social avoidance, anxiety-like behaviors, and the activation of astrocytes in the hippocampus. Interestingly, the overexpression of lipocalin 2 in the brain also altered the expression of stress-related genes, including monoamine oxidase A, monoamine oxidase B, mineralocorticoid receptor, and glucocorticoid receptor in the hippocampus. Conclusions This study suggests that the treatment of EA at Baihui (GV 20) and Dazhui (GV 14) acupoints improves RSDS-induced social avoidance, anxiety-like behaviors, astrocyte activation, and lipocalin 2 expression. Furthermore, our findings also indicate that lipocalin 2 expression in the brain may be an important biomarker for the development of PTSD-related symptoms.

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