Therapeutic Effects of a Novel Form of Biotin on Propionic Acid-Induced Autistic Features in Rats

Abstract

Magnesium biotinate (MgB) is a novel biotin complex with superior absorption and anti-inflammatory effects in the brain than D-Biotin. This study aimed to investigate the impact of different doses of MgB on social behavior deficits, learning and memory alteration, and inflammatory markers in propionic acid (PPA)-exposed rats. In this case, 35 Wistar rats (3 weeks old) were distributed into five groups: 1, Control; 2, PPA treated group; 3, PPA+MgBI (10 mg, HED); 4, PPA+MgBII (100 mg, HED); 5, PPA+MgBIII (500 mg, HED). PPA was given subcutaneously at 500 mg/kg/day for five days, followed by MgB for two weeks. PPA-exposed rats showed poor sociability and a high level of anxiety-like behaviors and cognitive impairments (p < 0.001). In a dose-dependent manner, behavioral and learning-memory disorders were significantly improved by MgB supplementation (p < 0.05). PPA decreased both the numbers and the sizes of Purkinje cells in the cerebellum. However, MgB administration increased the sizes and the densities of Purkinje cells. MgB improved the brain and serum Mg, biotin, serotonin, and dopamine concentrations, as well as antioxidant enzymes (CAT, SOD, GPx, and GSH) (p < 0.05). In addition, MgB treatment significantly regulated the neurotoxicity-related cytokines and neurotransmission-related markers. For instance, MgB significantly decreased the expression level of TNF-α, IL-6, IL-17, CCL-3, CCL-5, and CXCL-16 in the brain, compared to the control group (p < 0.05). These data demonstrate that MgB may ameliorate dysfunctions in social behavior, learning and memory and reduce the oxidative stress and inflammation indexes of the brain in a rat model.

Calcium voltage-gated channel subunit alpha 1 C and glial fibrillary acidic protein signaling pathways as a selective biomarker in predicting the efficacy of liposomal loaded co-enzyme Q in the autistic rat model

“…This is due to the antioxidant neuroprotective effect of both Co-Q10 and LCo-Q10, and increase brain mitochondrial concentrations in animal studies and reduces markers of oxidative damage in the cerebral cortex and hippocampus. The present findings is in agreement with the study reported by [3] that neuroglial activation together with a decrease in the number of cerebellar Purkinje cells and an increase in certain cytokines were investigated in ASD brain tissues. As reported previously, both humans and animals with ASD display altered structures and functions in various brain areas, such as the hippocampus [39] and the cortex [40] .…”

“…Furthermore, PPA can alter genes, related to autism pathogenesis, that controls neuroplasticity, oxidative stress, neurotransmitters, neurodevelopment, mitochondrial function and inflammation [2] . PPA can induce brain and behavioral disturbance in animal model identical to those of autistic human beings, via fluctuating brain FA metabolism [3] .…”

Lotusine ameliorates propionic acid‐induced autism spectrum disorder‐like behavior in mice by activating D1 dopamine receptor in medial prefrontal cortex

“…PPA administration in rats caused pathophysiological and clinical features similar to those seen in ASD patients (Ali et al, 2022;Khera et al, 2022;Sahin et al, 2022). Therefore, the PPA model serves as valid animal model to study the underlying neurobiology of ASD.…”

The Rationale for Vitamin, Mineral, and Cofactor Treatment in the Precision Medical Care of Autism Spectrum Disorder

“…Magnesium biotinate, a novel biotin complex with superior absorption, has been effective in decreasing the expression of neurotoxicity-related cytokines, improving the brain and serum magnesium, biotin, serotonin, and dopamine concentrations, and ameliorating dysfunctions in social behavior, learning, and memory in propionic acid-exposed rats with ASD behaviors [ 100 ]. A study conducted in the USA reported that biotin levels of ASD were 20% lower compared to neurotypical controls, and nearly 7% of those with ASD had biotin levels below the reference range [ 27 ].…”