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

In Gyoung Ju,Eugene Huh,Jong Kil Lee,Seung Ho Jeon,Jin Hee Kim,Mee Youn Lee,Choong Hwan Lee,Myung Sook Oh

doi:10.3390/nu12103027

In Gyoung Ju, Eugene Huh + Show 6 more

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https://doi.org/10.3390/nu12103027

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Journal: Nutrients	Publication Date: Oct 2, 2020
Citations: 7	License type: CC BY 4.0

Affiliation: Kyung Hee University, Konkuk University

Abstract

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.

Highlights

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder accompanied by inattention, impulse and hyperactivity that occurs in childhood and has a current prevalence of 5% in 4–17-year-old children [1,2]
HX106 treatment started from week 3 gradually improved the weight loss; it was not significantly different from the offspring affected by PAE (OPAE) group (Table 1)
We clearly presented that the metabolite profiles in plasma, liver, colon and feces were altered in the OPAE group and that the changed direction was reversed by the HX106 treatment

Summary

Introduction

Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder accompanied by inattention, impulse and hyperactivity that occurs in childhood and has a current prevalence of 5% in 4–17-year-old children [1,2]. It is known that prenatal alcohol exposure (PAE). PAE causes fetal alcohol spectrum disorders, which often co-occurs with. Clinical, neuroimaging and genetic studies suggest that catecholamines, especially dopamine, play an important role in the development of ADHD [7,8]. Dopamine transmission occurs in the prefrontal cortex, nucleus accumbens and striatum, mediating attention, cognition, motor control and motivation with regard to the pathology of ADHD [9]. It is known that genetic variants of dopamine transmission-related factors, such as dopamine transporters and dopamine receptors contribute to the development of ADHD [10]. To control the symptoms of ADHD, psychostimulants regulating dopamine signaling are frequently prescribed including methylphenidate, which blocks dopamine transporters (DAT) and norepinephrine transporters and amphetamine, which indirectly activates dopamine receptor D1 and adrenoceptor α2 [11,12,13]

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