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Kim HY, Lee YJ, Kim SJ, et al. Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model. J Toxicol Environ Health A. 2021;85(1):1-13doi: 10.1080/15287394.2021.1967821.
Kim, H. Y., Lee, Y. J., Kim, S. J., Lee, J. D., Kim, S., Ko, M. J., Kim, J. W., Shin, C. Y., & Kim, K. B. (2022). Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model. Journal of toxicology and environmental health. Part A, 85(1), 1-13. https://doi.org/10.1080/15287394.2021.1967821
Kim, Hyang Yeon, et al. "Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model." Journal of toxicology and environmental health. Part A vol. 85,1 (2022): 1-13. doi: https://doi.org/10.1080/15287394.2021.1967821
Kim HY, Lee YJ, Kim SJ, Lee JD, Kim S, Ko MJ, Kim JW, Shin CY, Kim KB. Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model. J Toxicol Environ Health A. 2022 Jan 02;85(1):1-13. doi: 10.1080/15287394.2021.1967821. Epub 2021 Aug 27. PMID: 34445937.
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J Toxicol Environ Health A. 2022 Jan 02;85(1):1-13. doi: 10.1080/15287394.2021.1967821. Epub 2021 Aug 27.

Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model.

Journal of toxicology and environmental health. Part A

Hyang Yeon Kim, Yong-Jae Lee, Sun Jae Kim, Jung Dae Lee, Suhkmann Kim, Mee Jung Ko, Ji-Woon Kim, Chan Young Shin, Kyu-Bong Kim

Affiliations

  1. College of Pharmacy, Dankook University, Cheonan, Chungnam, Republic of Korea.
  2. Center for Human Risk Assessment, Dankook University, Cheonan, Chungnam Republic of Korea.
  3. Department of Chemistry and Chemistry Institute for Functional Materials, Pusan National University, Busan Republic of Korea.
  4. Department Of Neuroscience, School Of Medicine, Konkuk University, Seoul, Republic of Korea.

PMID: 34445937 DOI: 10.1080/15287394.2021.1967821

Abstract

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Keywords: Metabolomics; autism spectrum disorders (ASD); rat; valproic acid (VPA)

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