Intervention mechanism of repeated oral GABA administration on anxiety-like behaviors induced by emotional stress in rats

He, Yongjian; Ouyang, Junyan; Hu, Zhuoyan; Yang, Jie; Chu, Yue; Huang, Shaowen; Yang, Yichao; Liu, Chunhong

doi:10.1016/j.psychres.2018.12.025

Cited by 24 publications

(10 citation statements)

References 54 publications

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“…Empty bottles are often used to induce an ES model in both rats and mice 23,24 . In the present study, the mice subjected to empty bottle intervention showed attacking behaviors, which were similar to those in patients with anxiety 25 .…”

Section: Discussionsupporting

confidence: 69%

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Wang

Zhang

et al. 2020

Journal of Leukocyte Biology

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Psoriasis is a common, chronic multifactorial inflammatory skin disease with both genetic and environmental components. A number of studies have suggested that psoriasis episodes are often preceded by stressful life events. Nevertheless, the underline mechanisms of stress in psoriasis remain unexplored. To address this question, we established an emotional stress mouse model induced by empty bottle stimulation, and applied imiquimod (IMQ), a ligand of TLR7/8 and effective potent immune activator, on the dorsal skin to induce psoriasis‐like lesions. We found that empty bottles induced emotional stress exaggerated and prolonged psoriasiform dermatitis, which appeared as more prominent epidermal hyperplasia in the emotional stress mice compared with the control mice. Higher mRNA expression of Il‐1β, Il‐17a, and Il‐22, as well as higher secretion of IL‐1β, IL‐12p40, IL‐17, and IL‐22 were observed in the skin lesion of emotional stress mice. The emotional stress condition and IMQ treatment synergistically led to higher expression levels of neurotransmitters and their receptors in the skin, especially substance P (SP), we also found that SP could stimulate DCs to secrete more IL‐23p40 in vitro. In addition, NK‐1R antagonist partially abrogated enhanced epidermal thickness and the level of neurotransmitters in emotional stress mice. Taken together, these results indicate that stress exacerbates and prolongs psoriasiform dermatitis in mice by up‐regulating IL‐1β and IL‐23p40, which were related to local DCs stimulated by abnormal SP.

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Section: Discussionsupporting

confidence: 69%

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Wang

Zhang

et al. 2020

Journal of Leukocyte Biology

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“…Supporting a critical role of GABA in COVID-19-associated pneumonia, GABA administration attenuates severity of disease and reduced rate of death in an experimental coronavirus mouse hepatitis virus (MHV)-1 pneumonia model [39]. GABA was administered orally to infected mice and the agent was safe and efficiently absorbed by oral administration in humans [40], indicating a potential prophylactic or therapeutic application of the amino acid in COVID-19 patients [41]. Moreover, GABA stabilizes endothelial metabolism by regulating ATP synthesis as well as fatty acid and pyruvate oxidation [42].…”

Section: Discussionmentioning

confidence: 99%

Disturbed lipid and amino acid metabolisms in COVID-19 patients

et al. 2022

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The Coronavirus disease 2019 (COVID-19) pandemic is overwhelming the healthcare systems. Identification of systemic reactions underlying COVID-19 will lead to new biomarkers and therapeutic targets for monitoring and early intervention in this viral infection. We performed targeted metabolomics covering up to 630 metabolites within several key metabolic pathways in plasma samples of 20 hospitalized COVID-19 patients and 37 matched controls. Plasma metabolic signatures specifically differentiated severe COVID-19 from control patients. The identified metabolic signatures indicated distinct alterations in both lipid and amino acid metabolisms in COVID-19 compared to control patient plasma. Systems biology-based analyses identified sphingolipid, tryptophan, tyrosine, glutamine, arginine, and arachidonic acid metabolism as mostly impacted pathways in COVID-19 patients. Notably, gamma-aminobutyric acid (GABA) was significantly reduced in COVID-19 patients and GABA plasma levels allowed for stratification of COVID-19 patients with high sensitivity and specificity. The data reveal large metabolic disturbances in COVID-19 patients and suggest use of GABA as potential biomarker and therapeutic target for the infection.

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“…To achieve this, three engineered L. lactis strains are designed to separately produce gamma-aminobutyric acid (GABA), granulocyte-colony stimulating factor (GCSF), or glucagon-like peptide-1 (GLP1) upon blue light exposure. The reason why we choose these three components is that they have been reported to work on anxiety behavior, − Parkinson’s disease, − and nerve signaling through oral administration. The recombinant bacteria are first delivered to the gut by an small-intestine-targeting and pH-sensitive microsphere system, which is then manipulated by an NIR-light triggered upconversion optogenetic nanosystem.…”

mentioning

confidence: 99%

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

et al. 2022

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The discovery of the gut–brain axis has proven that brain functions can be affected by the gut microbiota’s metabolites, so there are significant opportunities to explore new tools to regulate gut microbiota and thus work on the brain functions. Meanwhile, engineered bacteria as oral live biotherapeutic agents to regulate the host’s healthy homeostasis have attracted much attention in microbial therapy. However, whether this strategy is able to remotely regulate the host’s brain function in vivo has not been investigated. Here, we engineered three blue-light-responsive probiotics as oral live biotherapeutic agents. They are spatiotemporally delivered and controlled by the upconversion optogenetic micro–nano system. This micro–nano system promotes the small intestine targeting and production of the exogenous L. lactis in the intestines, which realizes precise manipulation of brain functions including anxiety behavior, Parkinson’s disease, and vagal afferent. The noninvasive and real-time probiotic intervention strategy makes the communiation from the gut to the host more controllable, which will enable the potential for engineered microbes accurately and effectively regulating a host’s health.

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Intervention mechanism of repeated oral GABA administration on anxiety-like behaviors induced by emotional stress in rats

Cited by 24 publications

References 54 publications

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Stress aggravates and prolongs imiquimod-induced psoriasis-like epidermal hyperplasis and IL-1β/IL-23p40 production

Disturbed lipid and amino acid metabolisms in COVID-19 patients

Light-Sensitive Lactococcus lactis for Microbe–Gut–Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System

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