Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats

Shida, Yukari; Endo, Hitoshi; Owada, Satoshi; Inagaki, Yutaka; Sumiyoshi, Hideaki; Kamiya, Akihide; Eto, Tomoo; Tatemichi, Masayuki

doi:10.1038/s41598-021-02591-7

Cited by 4 publications

(1 citation statement)

References 74 publications

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“…Excessive BCAA concentrations are considered toxic and can cause tissue damage, particularly in the CNS ( 338 ). Although exploratory studies remain in their infancy, evidence suggests that BCAA modulation may be useful in cognition disorders ( 339 – 341 ). Further research is required to determine the relationship between the GM, BCAAs, HPA axis, and cognition.…”

Section: Mechanisms and Pathways Of The Mgb Axismentioning

confidence: 99%

Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

2023

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Cognitive function in humans depends on the complex and interplay between multiple body systems, including the hypothalamic-pituitary-adrenal (HPA) axis. The gut microbiota, which vastly outnumbers human cells and has a genetic potential that exceeds that of the human genome, plays a crucial role in this interplay. The microbiota-gut-brain (MGB) axis is a bidirectional signalling pathway that operates through neural, endocrine, immune, and metabolic pathways. One of the major neuroendocrine systems responding to stress is the HPA axis which produces glucocorticoids such as cortisol in humans and corticosterone in rodents. Appropriate concentrations of cortisol are essential for normal neurodevelopment and function, as well as cognitive processes such as learning and memory, and studies have shown that microbes modulate the HPA axis throughout life. Stress can significantly impact the MGB axis via the HPA axis and other pathways. Animal research has advanced our understanding of these mechanisms and pathways, leading to a paradigm shift in conceptual thinking about the influence of the microbiota on human health and disease. Preclinical and human trials are currently underway to determine how these animal models translate to humans. In this review article, we summarize the current knowledge of the relationship between the gut microbiota, HPA axis, and cognition, and provide an overview of the main findings and conclusions in this broad field.

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Section: Mechanisms and Pathways Of The Mgb Axismentioning

confidence: 99%

Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

2023

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Superovulation with an anti-inhibin monoclonal antibody improves the reproductive performance of rat strains by increasing the pregnancy rate and the litter size

Mochida,

Morita,

Sasaoka

et al. 2024

Sci Rep

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Rats are multiparous rodents that have been used extensively in research; however, the low reproductive performance of some rat strains hampers the broader use of rats as a biomedical model. In this study, the possibility of increasing the litter size after natural mating in rats through superovulation using an anti-inhibin monoclonal antibody (AIMA) was examined. In outbred Wistar rats, AIMA increased the number of ovulated oocytes by 1.3-fold. AIMA did not affect fertilization and subsequent embryonic development, resulting in a 1.4-fold increase in litter size and a high pregnancy rate (86%). In contrast, conventional superovulation by eCG/hCG administration decreased the pregnancy rate to 6–40% and did not increase the litter size. In inbred Brown Norway rats, AIMA increased the litter size by 1.2-fold, and the pregnancy rate increased more than twice (86% versus 38% in controls). AIMA also increased the litter size by 1.5-fold in inbred Tokai High Avoiders and Fischer 344 rats. AIMA increased the efficiency of offspring production by 1.5-, 2.7-, 1.4-, and 1.4-fold, respectively, in the four rat strains. Thus, AIMA may consistently improve the reproductive performance through natural mating in rats, which could promote the use of AIMA in biomedical research.

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The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

Ekwudo,

Gubert,

Hannan

2024

The FEBS Journal

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Huntington's disease (HD) is a currently incurable neurogenerative disorder and is typically characterized by progressive movement disorder (including chorea), cognitive deficits (culminating in dementia), psychiatric abnormalities (the most common of which is depression), and peripheral symptoms (including gastrointestinal dysfunction). There are currently no approved disease‐modifying therapies available for HD, with death usually occurring approximately 10–25 years after onset, but some therapies hold promising potential. HD subjects are often burdened by chronic diarrhea, constipation, esophageal and gastric inflammation, and a susceptibility to diabetes. Our understanding of the microbiota–gut–brain axis in HD is in its infancy and growing evidence from preclinical and clinical studies suggests a role of gut microbial population imbalance (gut dysbiosis) in HD pathophysiology. The gut and the brain can communicate through the enteric nervous system, immune system, vagus nerve, and microbiota‐derived‐metabolites including short‐chain fatty acids, bile acids, and branched‐chain amino acids. This review summarizes supporting evidence demonstrating the alterations in bacterial and fungal composition that may be associated with HD. We focus on mechanisms through which gut dysbiosis may compromise brain and gut health, thus triggering neuroinflammatory responses, and further highlight outcomes of attempts to modulate the gut microbiota as promising therapeutic strategies for HD. Ultimately, we discuss the dearth of data and the need for more longitudinal and translational studies in this nascent field. We suggest future directions to improve our understanding of the association between gut microbes and the pathogenesis of HD, and other ‘brain and body disorders’.

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Branched-chain amino acids govern the high learning ability phenotype in Tokai high avoider (THA) rats

Cited by 4 publications

References 74 publications

Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

Signalling cognition: the gut microbiota and hypothalamic-pituitary-adrenal axis

Superovulation with an anti-inhibin monoclonal antibody improves the reproductive performance of rat strains by increasing the pregnancy rate and the litter size

The microbiota–gut–brain axis in Huntington's disease: pathogenic mechanisms and therapeutic targets

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