Title:Oxidative Stress and Nitric Oxide in Autism Spectrum Disorder and Other Neuropsychiatric Disorders
VOLUME: 15 ISSUE: 5
Author(s):Kunio Yui, Yohei Kawasaki, Hiroshi Yamada and Shintaro Ogawa
Affiliation:Research Institute of Pervasive Developmental Disorders, Ashiya University, 13-22 Rokurokusocho, Ashiya, 659-8511, Hyogo, Japan.
Keywords:Arachidonic acid, neuroprotective effects, neurotoxic effects, nitric oxide, oxidative stress, polyunsaturated fatty
acids, therapeutic potential.
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.
