N, N-Dimethylglycine decreases oxidative stress and improves &lt;i&gt;in vitro&lt;/i&gt; development of bovine embryos

Takahashi, T.; Sasaki, Kouya; Somfai, T.; Nagai, Takashi; Manabe, Noboru; Edashige, Keisuke

doi:10.1262/jrd.2015-149

Cited by 22 publications

(15 citation statements)

References 22 publications

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“…DMG is produced by metabolizing choline into glycine, and is a by-product of homocysteine metabolism where betaine is converted to methionine and DMG by betaine-homocysteine methyltransferase. Studies have shown that DMG decreases oxidative stress (Takahashi et al, 2016 ), improves immune response (Graber et al, 1981 ) and acts as anticonvulsant (Freed, 1985 ). Of note, the major portion of glycine and serine synthesis occurs in hepatic tissue via the “phosphorylated pathway,” therefore corresponding changes in brain may not be detectable in plasma.…”

Section: Discussionmentioning

confidence: 99%

Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

Stoessel

Schulte

Santos

et al. 2018

Front. Aging Neurosci.

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Parkinson's disease (PD) shows high heterogeneity with regard to the underlying molecular pathogenesis involving multiple pathways and mechanisms. Diagnosis is still challenging and rests entirely on clinical features. Thus, there is an urgent need for robust diagnostic biofluid markers. Untargeted metabolomics allows establishing low-molecular compound biomarkers in a wide range of complex diseases by the measurement of various molecular classes in biofluids such as blood plasma, serum, and cerebrospinal fluid (CSF). Here, we applied untargeted high-resolution mass spectrometry to determine plasma and CSF metabolite profiles. We semiquantitatively determined small-molecule levels (≤1.5 kDa) in the plasma and CSF from early PD patients (disease duration 0–4 years; n = 80 and 40, respectively), and sex- and age-matched controls (n = 76 and 38, respectively). We performed statistical analyses utilizing partial least square and random forest analysis with a 70/30 training and testing split approach, leading to the identification of 20 promising plasma and 14 CSF metabolites. These metabolites differentiated the test set with an AUC of 0.8 (plasma) and 0.9 (CSF). Characteristics of the metabolites indicate perturbations in the glycerophospholipid, sphingolipid, and amino acid metabolism in PD, which underscores the high power of metabolomic approaches. Further studies will enable to develop a potential metabolite-based biomarker panel specific for PD.

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Section: Discussionmentioning

confidence: 99%

Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

Stoessel

Schulte

Santos

et al. 2018

Front. Aging Neurosci.

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“…Dimethylglycine is oxidatively demethylated to form sarcosine 32 . It has been reported that N,N-dimethylglycine decreases oxidative stress 33 and improves immune responses 34 . Compared with the control group, emodin significantly increased the levels of N,N-dimethyglycine and betaine in the cell media samples and decreased the level of N,N-dimethyglycine in the cell extracts.…”

Section: Discussionmentioning

confidence: 99%

NMR-based Metabolomic Techniques Identify the Toxicity of Emodin in HepG2 Cells

Chang

Gao

Wang

et al. 2018

Sci Rep

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Emodin is a natural anthraquinone derivative that is present in various herbal preparations. The pharmacological effects of emodin include anticancer, hepatoprotective, anti-inflammatory, antioxidant and even antimicrobial activities. However, emodin also has been reported to induce hepatotoxicity, nephrotoxicity, genotoxicity and reproductive toxicity. The mechanism of emodin’s adverse effects is complicated and currently not well understood. This study aimed to establish a cell metabonomic method to investigate the toxicity of emodin and explore its potential mechanism and relevant targets. In the present study, metabonomic profiles of cell extracts and cell culture media obtained using the 1H NMR technique were used to assess emodin toxicity in HepG2 cells. Multivariate statistical analyses such as partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) were used to characterize the metabolites that differed between the control and emodin groups. The results indicated that emodin resulted in differences in 33 metabolites, including acetate, arginine, aspartate, creatine, isoleucine, leucine and histidine in the cell extract samples and 23 metabolites, including alanine, formate, glutamate, succinate and isoleucine, in the cell culture media samples. Approximately 8 pathways associated with these metabolites were disrupted in the emodin groups. These results demonstrated the potential for using cell metabonomics approaches to clarify the toxicological effects of emodin, the underlying mechanisms and potential biomarkers. Our findings may help with the development of novel strategies to discover targets for drug toxicity, elucidate the changes in regulatory signal networks and explore its potential mechanism of action.

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“…A previous study showed that NMDAR is critical to develop and rescue of ASD-like phenotypes observed in Shank2-mutant mice, and that, by modulating NMDAR, metabotropic glutamate receptor 5 can be a novel treatment target for ASD (38). DMG derivatives also have pharmacological activities in the central nervous system, and decrease oxidative stress (39), improve immune responses (40), and exhibit anticonvulsant activity in animal models (41). Psychotropic effects of DMG have also been reported by an animal study as having an antidepressant-like effect with reduction in ketamine-induced psychotomimetic behaviors (42).…”

Section: Discussionmentioning

confidence: 99%

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

Kato

Kuwabara

Okada

et al. 2020

Preprint

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Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)

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N, N-Dimethylglycine decreases oxidative stress and improves <i>in vitro</i> development of bovine embryos

Cited by 22 publications

References 22 publications

Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

Promising Metabolite Profiles in the Plasma and CSF of Early Clinical Parkinson's Disease

NMR-based Metabolomic Techniques Identify the Toxicity of Emodin in HepG2 Cells

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

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