Sodium butyrate improves memory and modulates the activity of histone deacetylases in aged rats after the administration of d-galactose

Garcez, Michelle Lima; Carvalho, Carlos Alberto de; Mina, Francielle; Bellettini-Santos, Tatiani; Schiavo, Gustavo Luis; Silva, Sabrina da; Campos, Ana Carolina Brunatto Falchetti; Varela, Roger B.; Valvassori, Samira S.; Damiani, Adriani Paganini; Longaretti, Luiza Martins; Andrade, Vanessa Moraes de; Budni, Josiane

doi:10.1016/j.exger.2018.10.005

Cited by 27 publications

(13 citation statements)

References 57 publications

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“…Moreover, other studies have shown beneficial effects of butyrate and probiotic treatment on cognition and memory in a D-galactose model of aging, a condition known to correlate with AD occurrence and progression (137,167). The model consists of a long term administration of Dgalactose, which can readily be metabolized but eventually leads to an overproduction of reactive oxygen species, thus causing genetic and cell damage impairing cognition (137,168). Finally, through HDAC inhibition, butyrate administration recovered memory function and increased expression of genes implicated in associative learning in the APP/PS1 mouse model of AD (158).…”

Section: Scfas and Alzheimer's Diseasementioning

confidence: 98%

“…Given the HDAC inhibition property of SCFAs, several animal studies have focused mainly on the use of butyrate to elevate histone acetylation in the brain during a critical phase of memory formation. These studies have reported an enhancement of long-term potentiation (LTP) and contextual fear memory induced by HDAC inhibition (124,127,136,137), pointing out enteric SCFAs as a promising learning and memory modulators. Therefore, the discovery that the microbiota can influence brain physiology has led to a plethora of experiments involving neurological disorders.…”

Section: Scfas and Brain Disordersmentioning

confidence: 99%

“…Accordingly, the 3xTg mouse model of AD treated with probiotics in the early stage showed a promising reduction of inflammatory cytokines and decreased cognitive decline associated with reduced brain damage and Aβ aggregate accumulation (166). Moreover, other studies have shown beneficial effects of butyrate and probiotic treatment on cognition and memory in a D-galactose model of aging, a condition known to correlate with AD occurrence and progression (137,167). The model consists of a long term administration of Dgalactose, which can readily be metabolized but eventually leads to an overproduction of reactive oxygen species, thus causing genetic and cell damage impairing cognition (137,168).…”

Section: Scfas and Alzheimer's Diseasementioning

confidence: 99%

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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

2020

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A substantial body of evidence supports that the gut microbiota plays a pivotal role in the regulation of metabolic, endocrine and immune functions. In recent years, there has been growing recognition of the involvement of the gut microbiota in the modulation of multiple neurochemical pathways through the highly interconnected gut-brain axis. Although amazing scientific breakthroughs over the last few years have expanded our knowledge on the communication between microbes and their hosts, the underpinnings of microbiota-gut-brain crosstalk remain to be determined. Short-chain fatty acids (SCFAs), the main metabolites produced in the colon by bacterial fermentation of dietary fibers and resistant starch, are speculated to play a key role in neuro-immunoendocrine regulation. However, the underlying mechanisms through which SCFAs might influence brain physiology and behavior have not been fully elucidated. In this review, we outline the current knowledge about the involvement of SCFAs in microbiota-gut-brain interactions. We also highlight how the development of future treatments for central nervous system (CNS) disorders can take advantage of the intimate and mutual interactions of the gut microbiota with the brain by exploring the role of SCFAs in the regulation of neuro-immunoendocrine function.

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Section: Scfas and Alzheimer's Diseasementioning

confidence: 98%

Section: Scfas and Brain Disordersmentioning

confidence: 99%

Section: Scfas and Alzheimer's Diseasementioning

confidence: 99%

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The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

2020

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“…SCFAs, mainly comprised of acetate, propionate, and butyrate, function through either G-protein-coupled receptors (GPCRs) or histone deacetylases (HDACs) (36,37). Taking into consideration, the HDAC inhibition activity of SCFAs, several studies have reported an enhancement of memory functions through the increased long-term potentiation through HDAC inhibition by butyrate (38)(39)(40). However, mice deficient in SCFAs receptor Free fatty acid receptor 2 (FFAR2)--normally not expressed in the brain-show comparable hyper-ramified morphological phenotype while microglia density remains unaffected, suggesting a partial signal relay mediated by peripheral FFAR2-expressing cells (34).…”

Section: Gut Microbiota Modulates Prenatal and Adult Microgliamentioning

confidence: 99%

The microbiota–microglia axis in central nervous system disorders

Mossad

Erny

2020

Brain Pathology

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The innate immune system in the central nervous system (CNS) is mainly represented by specialized tissue‐resident macrophages, called microglia. In the past years, various species‐, host‐ and tissue‐specific as well as environmental factors were recognized that essentially affect microglial properties and functions in the healthy and diseased brain. Host microbiota are mostly residing in the gut and contribute to microglial activation states, for example, via short‐chain fatty acids (SCFAs) or aryl hydrocarbon receptor (AhR) ligands. Thereby, the gut microorganisms are deemed to influence numerous CNS diseases mediated by microglia. In this review, we summarize recent findings of the interaction between the host microbiota and the CNS in health and disease, where we specifically highlight the resident gut microbiota as a crucial environmental factor for microglial function as what we coin “the microbiota‐microglia axis.”

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“…SB has been studied for its neuroprotective effect in an AD mouse model 32 and in vitro [33][34][35] where it has shown an ability to protect against DNA damage in aged mice. 36,37 Low levels of key butyrate-producing bacteria, in addition to higher relative abundances of taxa known to cause pro-inflammatory states, were found in stool samples from AD patients in comparison with samples from non-dementia subjects. 38 Although the evidence suggests that IPA and SB have protective effects with potential therapeutic implications for neurodegenerative diseases, there are no studies evaluating the anti-inflammatory effects of these compounds in vitro on human primary astrocytes.…”

mentioning

confidence: 99%

Sodium Butyrate and Indole-3-propionic Acid Prevent the Increase of Cytokines and Kynurenine Levels in LPS-induced Human Primary Astrocytes

Garcez

Tan

Heng

et al. 2020

Int J�Tryptophan�Res

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The crosstalk between central nervous system (CNS) and gut microbiota plays key roles in neuroinflammation and chronic immune activation that are common features of all neurodegenerative diseases. Imbalance in the microbiota can lead to an increase in the intestinal permeability allowing toxins to diffuse and reach the CNS, as well as impairing the production of neuroprotective metabolites such as sodium butyrate (SB) and indole-3-propionic acid (IPA). The aim of the present study was to evaluate the effect of SB and IPA on LPS-induced production of cytokines and tryptophan metabolites in human astrocytes. Primary cultures of human astrocytes were pre-incubated with SB or IPA for 1 hour before treatment with LPS. Cell viability was not affected at 24, 48 or 72 hours after pre-treatment with SB, IPA or LPS treatment. SB was able to significantly prevent the increase of GM-CSF, MCP-1, IL-6 IL-12, and IL-13 triggered by LPS. SB and IPA also prevented inflammation indicated by the increase in kynurenine and kynurenine/tryptophan ratio induced by LPS treatment. IPA pre-treatment prevented the LPS-induced increase in MCP-1, IL-12, IL-13, and TNF-α levels 24 hours after pre-treatment, but had no effect on tryptophan metabolites. The present study showed for the first time that bacterial metabolites SB and IPA have potential anti-inflammatory effect on primary human astrocytes with potential therapeutic benefit in neurodegenerative disease characterized by the presence of chronic low-grade inflammation.

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Sodium butyrate improves memory and modulates the activity of histone deacetylases in aged rats after the administration of d-galactose

Cited by 27 publications

References 57 publications

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication

The microbiota–microglia axis in central nervous system disorders

Sodium Butyrate and Indole-3-propionic Acid Prevent the Increase of Cytokines and Kynurenine Levels in LPS-induced Human Primary Astrocytes

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