3-nitrotyrosine and Autistic-Disorder

Autism spectrum disorder (ASD) is a neurodevelopmental disorder where immune cells play an important role. Oxidants and pro-inflammatory cytokines generated by innate immune cells have been implicated in the pathogenesis of ASD. Many previous reports have shown the role of various enzymatic antioxidants in the plasma/red blood cells of ASD subjects, however no study so far has evaluated them in peripheral immune cells of innate origin (neutrophils and monocytes) in ASD patients and typically developing control (TDC) children. With this background, our study explored the expression and activities of major enzymatic antioxidants such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) in peripheral neutrophils and monocytes of TDC/ASD subjects. Our data show that expression and activity of SOD is increased in ASD subjects as compared to TDC children in neutrophils and monocytes. On the other hand, GPx/GR activity is either reduced/unaltered in neutrophils and monocytes of ASD subjects as compared to TDC children. Increased SOD expression is associated with upregulated expression of nitrotyrosine (a marker of oxidant damage) in both innate immune cells of ASD subjects. Our study suggests that despite adaptive antioxidant response, there is an increased oxidative burden in peripheral neutrophils and monocytes of ASD subjects. This suggests that dysregulated enzymatic antioxidant network in peripheral innate immune cells could play a significant role in the pathogenesis of autism.

Topics: Antioxidants; Autistic Disorder; Child; Child, Preschool; Correlation of Data; Cross-Sectional Studies; Female; Flow Cytometry; Glutathione Peroxidase; Glutathione Reductase; Humans; Male; Monocytes; Neutrophils; Psychiatric Status Rating Scales; Superoxide Dismutase; Tyrosine

Butyl paraben is a preservative used in food, drugs and cosmetics. Neurotoxic effect was reported recently beside the potential estrogenic activity of parabens. There is controversy as to the potential harmful effects of butyl parabens, which are suspected to contribute to autism and learning disabilities. The purpose of this study was to examine the similarities between paraben intoxication signs in the rat brain and brain markers in an autistic like rat model. This study provides evidence of many parallels between the two, including (1) oxidative stress, (2) decreased reduced glutathione levels and elevated oxidised glutathione, (3) mitochondrial dysfunction, and (4) neuroinflammation and increased pro-inflammatory cytokine levels in the brain (tumour necrosis factor-alpha, interleukin-1-beta, and interleukin-6). (5) Increased protein oxidation reported by a significant increase in 3-nitrotyrosine (3-NT)/tyrosine ratio. (6) A marked disturbance was found in the production of energy carriers (AMP, ATP and AMP/ATP ratio) in comparison with the control. The evidence suggests that paraben may, to some extent, either cause or contribute to the brain physiopathology in ASDs or pathogens that produce the brain pathology observed in the diagnosed rat model of ASD.

Topics: Adenosine Monophosphate; Adenosine Triphosphate; Animals; Autistic Disorder; Biomarkers; Brain; Brain Diseases; Chromatography, High Pressure Liquid; Female; Glutathione; Glutathione Disulfide; Inflammation Mediators; Interleukin-1beta; Interleukin-6; Male; Mitochondria; Oxidative Stress; Parabens; Pregnancy; Rats, Wistar; Tumor Necrosis Factor-alpha; Tyrosine; Valproic Acid