GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study,...

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Main Authors: In Gyoung Ju, Mee Youn Lee, Seung Ho Jeon, Eugene Huh, Jin Hee Kim, Jong Kil Lee, Choong Hwan Lee, Myung Sook Oh
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/12/10/3027
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author In Gyoung Ju
Mee Youn Lee
Seung Ho Jeon
Eugene Huh
Jin Hee Kim
Jong Kil Lee
Choong Hwan Lee
Myung Sook Oh
author_facet In Gyoung Ju
Mee Youn Lee
Seung Ho Jeon
Eugene Huh
Jin Hee Kim
Jong Kil Lee
Choong Hwan Lee
Myung Sook Oh
author_sort In Gyoung Ju
collection DOAJ
description Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study, we hypothesized that metabolic disturbance would involve in ADHD neuropathology and aimed to investigate the changes in metabolite profile in PAE-induced ADHD-like model and the effects of HX106, a nutraceutical, on ADHD-like pathophysiology and metabolite changes. To this end, we administered HX106 to the mouse offspring affected by PAE (OPAE) and assessed the hyperactivity using the open field test. We observed that HX106-treated OPAE showed less hyperactive behavior than vehicle-treated OPAE. The effects of HX106 were found to be related to the regulation of dopamine transporter and D2 dopamine receptor expression. Furthermore, using gas chromatography time-of-flight mass spectrometry-based metabolomics, we explored the metabolite changes among the experimental groups. The metabolite profile, particularly related with the amino acids, linoleic acid and amino sugar pathways, was altered by PAE and reversed by HX106 treatment partially similar to that observed in the control group. Overall, this study suggest that metabolite alteration would be involved in ADHD pathology and that HX106 can be an efficient supplement to overcome ADHD by regulating dopamine signaling-related protein expression and metabolite changes.
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spelling doaj.art-c8ac38a943614d1ab05073fa60de33a52023-11-20T15:56:41ZengMDPI AGNutrients2072-66432020-10-011210302710.3390/nu12103027GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed MiceIn Gyoung Ju0Mee Youn Lee1Seung Ho Jeon2Eugene Huh3Jin Hee Kim4Jong Kil Lee5Choong Hwan Lee6Myung Sook Oh7Department of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Fundamental Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Fundamental Pharmaceutical Science, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Bioscience and Biotechnology, Konkuk University, Seoul 05029, KoreaDepartment of Life and Nanopharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul 02447, KoreaAttention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that occurs in children characterized by inattention and hyperactivity. Prenatal alcohol exposure (PAE) can disrupt fetal neuronal development and cause an ADHD-like hyperactive behavior in the offspring. In this study, we hypothesized that metabolic disturbance would involve in ADHD neuropathology and aimed to investigate the changes in metabolite profile in PAE-induced ADHD-like model and the effects of HX106, a nutraceutical, on ADHD-like pathophysiology and metabolite changes. To this end, we administered HX106 to the mouse offspring affected by PAE (OPAE) and assessed the hyperactivity using the open field test. We observed that HX106-treated OPAE showed less hyperactive behavior than vehicle-treated OPAE. The effects of HX106 were found to be related to the regulation of dopamine transporter and D2 dopamine receptor expression. Furthermore, using gas chromatography time-of-flight mass spectrometry-based metabolomics, we explored the metabolite changes among the experimental groups. The metabolite profile, particularly related with the amino acids, linoleic acid and amino sugar pathways, was altered by PAE and reversed by HX106 treatment partially similar to that observed in the control group. Overall, this study suggest that metabolite alteration would be involved in ADHD pathology and that HX106 can be an efficient supplement to overcome ADHD by regulating dopamine signaling-related protein expression and metabolite changes.https://www.mdpi.com/2072-6643/12/10/3027attention deficit hyperactivity disorderhyperactivitynutraceuticalHX106metabolomics
spellingShingle In Gyoung Ju
Mee Youn Lee
Seung Ho Jeon
Eugene Huh
Jin Hee Kim
Jong Kil Lee
Choong Hwan Lee
Myung Sook Oh
GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
Nutrients
attention deficit hyperactivity disorder
hyperactivity
nutraceutical
HX106
metabolomics
title GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
title_full GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
title_fullStr GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
title_full_unstemmed GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
title_short GC-TOF-MS-Based Metabolomic Analysis and Evaluation of the Effects of HX106, a Nutraceutical, on ADHD-Like Symptoms in Prenatal Alcohol Exposed Mice
title_sort gc tof ms based metabolomic analysis and evaluation of the effects of hx106 a nutraceutical on adhd like symptoms in prenatal alcohol exposed mice
topic attention deficit hyperactivity disorder
hyperactivity
nutraceutical
HX106
metabolomics
url https://www.mdpi.com/2072-6643/12/10/3027
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