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

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.

Novel Interventions on Comorbidities in Patients with Fetal Alcohol Spectrum Disorder (FASD): An Integrative Review

“…Others, like DHA and papaverine, improved ethanol-induced deficits in behavior and neurodevelopmental markers [ 53 , 54 ]. Additionally, some interventions, such as HX106 and DAT inhibitor CE-123, improved enhanced cognitive abilities and regulated dopamine-related receptors in PAE animals [ 55 , 56 ].…”

Peripheral metabolic alterations associated with pathological manifestations of Parkinson’s disease in gut-brain axis-based mouse model

“…The conditions of GC-TOF-MS analysis were described based on a previous study ( Ju et al, 2020 ). GC-TOF-MS analysis was performed using an Agilent 7890A GC system (Palo Alto, CA, United States) coupled with a Leco TOF Pegasus III mass spectrometer.…”

“…The GC-TOF-MS raw data processing and multivariate statistical analysis were conducted as described in our previous study ( Ju et al, 2020 ). Raw data were converted to NetCDF format (*.cdf) using ChromaTOF (version 4.44, LECO).…”

Aerial part of Houttuynia cordata reverses memory impairment by regulating amyloid beta accumulation and neuroinflammation in Alzheimer's disease model

“…Western blotting was performed as previously described (Ju et al, 2020). Brain tissues were homogenized in RIPA buffer containing protease/phosphatase inhibitors.…”