Pipecolic acid enhancement of GABA response in single neurons of rat brain

Takahama, Kazuo; Hashimoto, Tadatoshi; Wang, M.-W.; Akaike, Norio; Hitoshi, Taizo; Okano, Yoshiro; Kasé, Yoshitoshi; Miyata, Takeshi

doi:10.1016/0028-3908(86)90263-7

Cited by 24 publications

(12 citation statements)

References 11 publications

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“…Considering the function of taurine as an osmolyte, this result suggests high importance of cell volume regulation for neuron's survival. Accumulated data also shows a significant neuroprotective role of taurine against stroke pathophysiology [40].…”

Section: Discussionmentioning

confidence: 97%

Hippocampal Sector–Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance

et al. 2020

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The gerbil is a well-known model for studying cerebral ischemia. The CA1 of the hippocampus is vulnerable to 5 min of ischemia, while the CA2–4 and dentate gyrus (DG) are resistant to it. Short-lasting ischemia, a model of transient ischemic attacks in men, results in CA1 neuron death within 2–4 days of reperfusion. Untargeted metabolomics, using LC-QTOF-MS, was used to enrich the knowledge about intrinsic vulnerability and resistance of hippocampal regions and their early post-ischemic response (IR). In total, 30 significant metabolites were detected. In controls, taurine was significantly lower and guanosine monophosphate was higher in CA1, as compared to that in CA2–4,DG. LysoPG and LysoPE were more abundant in CA1, while LysoPI 18:0 was detected only in CA2–4,DG. After IR, a substantial decrease in the citric acid level in CA1, an accumulation of pipecolic acid in both regions, and opposite changes in the amount of PE and LysoPE were observed. The following metabolic pathways were identified as being differentially active in control CA1 vs. CA2–4,DG: metabolism of taurine and hypotaurine, glycerophospholipid, and purine. These results may indicate that a regulation of cell volume, altered structure of cell membranes, and energy metabolism differentiate hippocampal regions. Early post-ischemia, spatial differences in the metabolism of aminoacyl-tRNA biosynthesis, and amino acids and their metabolites with a predominance of those which upkeep their well-being in CA2–4,DG are shown. Presented results are consistent with genetic, morphological, and functional data, which may be useful in further study on endogenous mechanisms of neuroprotection and search for new targets for therapeutic interventions.

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Section: Discussionmentioning

confidence: 97%

Hippocampal Sector–Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance

et al. 2020

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“…Pipecolic acid is a major metabolic intermediate of lysine [37], although we could not measure serotonin levels in epi WAT in the current study. In the brain, pipecolic acid enhances GABA response [38]. In addition, antagonist of GABA receptor restored suppressed food intake by pipecolic acid [39], indicating that pipecolic acid activates GABA receptors.…”

Section: Discussionmentioning

confidence: 92%

Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid

Nishitani

Fukuhara

Jinno

et al. 2018

Exp Clin Endocrinol Diabetes

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Eicosapentaenoic acid (EPA) is an omega-3 fatty acid with anti-inflammatory effects. To determine the effects of EPA on metabolic pathways in obese adipose tissues and liver, mice were fed normal chow diet (NCD), high-fat diet (HFD), or 3% EPA-containing high fat diet (HFD+EPA) for 8 weeks. Metabolomic analysis was performed using epididymal adipose tissues (epi WAT) and liver. Metabolites that were specifically elevated in HFD+EPA, were assessed for their anti-inflammatory properties using RAW264.7 macrophage cells. Body and adipose tissue weights were significantly higher in HFD than NCD, and lower in HFD+EPA than HFD. Plasma insulin levels were significantly higher in HFD than NCD, and lower in HFD+EPA compared with HFD. Plasma monocyte chemotactic protein-1 (MCP-1) levels were higher in HFD than NCD, and tended to be lower in HFD+EPA than HFD. The levels of intermediate metabolites in the glycolytic pathways were lower in HFD compared with NCD and HFD+EPA in both epi WAT and liver, while intermediate metabolites of the TCA cycles were elevated in HFD and HFD+EPA compared with NCD in epi WAT. Among the metabolites in epi WAT, the levels of thiaproline, phenaceturic acid, and pipecolic acid were specifically elevated in HFD+EPA, but not in HFD or NCD. Treatment of RAW264.7 cells with thiaproline significantly ameliorated LPS-induced iNOS expression, while pipecolic acid inhibited LPS-induced IL-1β expression. These results suggest that EPA normalizes glycolytic pathway intermediates in both epi WAT and liver, and induces metabolites with anti-inflammatory properties.

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“…In our multi-omics integration analysis, we focused on ATP and pipecolic acid, in addition to butyrate, since there is evidence supporting their role in CNS and they can be microbially derived (12,(48)(49)(50)(51)(52)(53)(54).…”

Section: Discussionmentioning

confidence: 99%

An integrated metagenomics and metabolomics approach implicates the microbiome-gut-brain-axis in the pathogenesis of Huntington’s disease transgenic mice

Kong¹,

Ellul²,

Narayana³

et al. 2020

Preprint

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Background: Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder with onset and severity of symptoms influenced by various environmental factors. Recent discoveries have highlighted the importance of the gastrointestinal microbiome in mediating the bidirectional communication between the central and enteric nervous system via circulating factors. Using shotgun sequencing, we investigated the gut microbiome composition in the R6/1 transgenic mouse model of HD from 4 to 12 weeks of age (early adolescent through to adult stages). Targeted metabolomics was also performed on the blood plasma of these mice (n=9 per group) at 12 weeks of age to investigate potential effects of gut dysbiosis on the plasma metabolome profile. The short-chain fatty acid (SCFA) concentrations in the plasma were validated using LCMS. Results: Beta diversity differed between HD mice compared to their WT littermates at 12 weeks of age, suggesting that gut dysbiosis occurs prior to overt motor symptoms. Modelled time profiles of each species, KEGG Orthologs and bacterial genes, revealed heightened volatility in the HD mice, indicating potential early effects of HD mutation in the gut prior to significant cognitive and motor dysfunction. In addition to gut dysbiosis at 12 weeks of age, we also found functional differences between the WT and HD mice. The butanoate metabolism pathway, which leads to the production of the protective short-chain fatty acid, butyrate, was increased in the gut. However, the plasma concentration of butyrate and propionate were both decreased in the HD mice, as determined by the SCFA validation. The concentrations of ATP were increased by over 4-fold in the HD plasma, which was contrary to expectations. The statistical integration of the metagenomics and metabolomics unraveled several Bacteroides species that were positively correlated with butyrate levels, and negatively correlated with ATP and pipecolic acid in the plasma. Blautia producta and Prevotella scopos were found to be negatively correlated with the butyrate and ATP respectively. Conclusions: Our study has revealed a previously unknown relationship between the gut bacteria and plasma metabolome, suggesting the potential role of gut in modulating the pathogenesis of HD via specific altered plasma metabolites which mediate gut-brain signalling.

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Pipecolic acid enhancement of GABA response in single neurons of rat brain

Cited by 24 publications

References 11 publications

Hippocampal Sector–Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance

Hippocampal Sector–Specific Metabolic Profiles Reflect Endogenous Strategy for Ischemia-Reperfusion Insult Resistance

Metabolomic Analysis of Diet-Induced Obese Mice Supplemented with Eicosapentaenoic Acid

An integrated metagenomics and metabolomics approach implicates the microbiome-gut-brain-axis in the pathogenesis of Huntington’s disease transgenic mice

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