Oxidative Stress and Nitric Oxide in Autism Spectrum Disorder and Other Neuropsychiatric Disorders

Abstract

The etiology of autism spectrum disorder (ASD) remains unclear; however, the toxic environmental exposure to oxidative stress has been suggested to play an important role in its pathogenesis. A loss of balance between oxidative stress and antioxidant capacity produces an excess of reactive nitrogen species (RNS) such as nitric oxide (NO). Polyunsaturated fatty acids (PUFAs), particularly arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, are closely related to NO and NO synthase. In the pathophysiology of ASD, NO is related to the activity of primary PUFAs. NO modulates short- and long-term synaptic plasticity and plays essential roles in the regulation of a wide range of physiological processes including neurotransmission. NO affects the function of reactive oxygen species (ROS) in the local cellular milieu, in which biological antioxidants are present. NO plays a double role in the organism showing both neuroprotective and neurotoxic effects. Redox imbalance leads to the activation of the neurotoxic pathway, suggesting crossroads for the neurotoxic or neuroprotective effects of NO. Furthermore, the dual role of NO could depend on the adaptive functions of the antioxidant capacity and oxidative stress-related ROS/RNS as the disease progresses. Increased concentrations of arachidonic acid promote neuronal survival, and the dysregulation of the NO system plays an important role in the pathophysiology of bipolar disorder and recurrent depressive disorders. Therefore, the NO system could provide useful drug targets for these diseases. NO and NO donors also show therapeutic potential for Alzheimer's disease and schizophrenia with refractory symptoms and cognitive dysfunction.

Association between preeclampsia and autism spectrum disorder: a population‐based study

“…Preeclampsia is one of the leading causes of maternal morbidity and mortality and has recently been redefined by the International Society for the Study of Hypertension in Pregnancy (ISSHP) as newonset hypertension (blood pressure ≥140/90 mmHg on/after 20 weeks' gestation) accompanied by proteinuria and/or other maternal organ dysfunction and/or uteroplacental dysfunction (Brown et al, 2018). Preeclampsia is associated with maternal inflammation, poor placentation and oxidative stress, which may also represent some of the potential aetiological pathways in the development of ASD (Brown et al, 2014;Nomura et al, 2017;Yui, Kawasaki, Yamada, & Ogawa, 2016).…”

Sub-acute restraint stress progressively increases oxidative/nitrosative stress and inflammatory markers while transiently upregulating antioxidant gene expression in the rat hippocampus

“…A recent wealth of evidence has demonstrated that free radicals, and most notably NO, play a crucial role in the regulation of stress effects and may be directly involved in the pathophysiology of stress-related disorders [13][14][15][16][17]. Under normal conditions, NO produced by the neuronal isoform of nitric oxide synthase (nNOS) is an important neurotransmitter associated with synaptic plasticity, memory formation, and neurotransmitter release [18,19].…”

A comparative study of the oxidative stress indices of children with autism and healthy children

“…The majority of studies indicate higher oxidant factors in children with autism. 20,21 Increased nitric oxide (NO) has been consistently demonstrated. 20 Increased thiobarbituric acid reactive substances (TBARS), the degradation products of fats, and increased xanthine oxidase activity in red blood cells have also been reported in autistic patients, 21 as have higher levels of the lipid peroxidation biomarker 8-isoprostane (8-iso-PGF2α).…”

“…20,21 Increased nitric oxide (NO) has been consistently demonstrated. 20 Increased thiobarbituric acid reactive substances (TBARS), the degradation products of fats, and increased xanthine oxidase activity in red blood cells have also been reported in autistic patients, 21 as have higher levels of the lipid peroxidation biomarker 8-isoprostane (8-iso-PGF2α). 19 Higher levels of these compounds in autistic individuals are clear indicators of elevated oxidants which may lead to cell degradation and death.…”