Title : Trace elements as modulators of oxidative stress markers: Influence on neurotransmitters in neurodevelopmental disorders
Abstract:
Neurodevelopmental Disorders (NDDs) are disabilities primarily caused by impairment of the neurological system and brain functioning. They are characterized by impairments in cognition, communication, behavior and/or motor skills as a result of abnormal brain development usually manifesting in infancy. Autism Spectrum Disorder (ASD) and Cerebral Palsy (CP) are prominent members of these disorders. Aside equivocal results of several studies associating genetic modulation with exposure to environmental toxicants as the etiogenesis of ASD and CP, the interplay of exposure to environmental toxicants (essential and toxic trace elements) with neurotransmitters and their effect on neurodevelopmental disorders remain a medical challenge. This work investigated levels of some essential and toxic elements along with levels of neurotransmitters including oxidative stress markers in children with ASD and CP. Seventy-five children were recruited; twenty-five each of which were clinically diagnosed as ASD, CP and Neuro-typical (NT) children respectively; their blood samples were collected. Essential and toxic metals (calcium, magnesium, selenium, zinc, copper, lead, aluminium, arsenate) using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS); neurotransmitters (glutamine, glutamate, GABA) using ELISA and Biomarkers of oxidative stress [Malondialdehyde (MDA), Total Antioxidant Capacity (TAC), Total Plasma Peroxide (TPP)] using spectrophotometry were analyzed in the collected blood. Oxidative Stress Index (OSI) was calculated (TPP/TAC). In ASD, CP and NT, plasma calcium (7.9±1.4; 7.7±1; 9.8±1.3 mg/dL), magnesium (2.5±0.5; 2.8±0.6; 3.1±0.4 mg/dL), selenium (40.8±7.9; 27.6±6.8; 59.0±5.3 µg/dL), zinc (222.3±63.8; 233.8±105.3; 438.5±185.5 µg/dL), copper (4.3±1.0; 4.0±0.8; 4.9±0.9 µg/dL) and Zn/Cu ratio were significantly reduced in ASD and CP compared to in NT children. Conversely, lead (9.5±4.0; 11.1±5.8; 5.4±2.05 µg/dL) and manganese (0.2±0.2; 0.2±0.2; 0.1±0.1µg/dL) levels were significantly elevated in ASD and CP compared to NT. However, selenium level was significantly reduced in CP compared to ASD and NT. Glutamine levels (379.2±53.1; 296.3±59.6; 419.1±71.8µmol/l) decreased significantly in ASD and CP compared to NT. Glutamate (1.9±0.12; 1.8±0.3; 1.7±0.3nmol/ml) and GABA (2.1±0.3; 1.8±0.4; 1.8±0.3µmol/l) levels were significantly elevated in ASD compared to CP and NT. OSI (0.4±0.1; 0.6±0.2; 0.4±0.1) and TPP (105.9±2.3; 115.1±8.5; 110.4±7.9) levels were significantly higher and TAC (280.2±34.4; 209.8±57.9; 303.8±33.1) was significantly reduced in CP compared to ASD and NT. The MDA (2.3±0.2; 2.1±0.2; 1.4±0.1) level was significantly elevated in ASD and CP compared to NT. Manganese and copper positively correlated with GABA and glutamine. Although, magnesium correlated negatively with GABA in ASD, Copper correlated positively with glutamate in CP. Oxidative stress was induced in children with Autism Spectrum Disorders and Cerebral Palsy due to reduction in essential metals. This stress may promote abnormal excitatory activities of neurons causing hyperglutermatagic and hypergabagic symptoms associated with the disorders.
