scholarly journals Oxidative Stress, Folate Receptor Autoimmunity, and CSF Findings in Severe Infantile Autism

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Vincent T. Ramaekers ◽  
Jeffrey M. Sequeira ◽  
Beat Thöny ◽  
Edward V. Quadros
Keyword(s):  
Oxidative Stress ◽  
Folate Receptor ◽  
Regulation Of Gene Expression ◽  
Reactive Oxygen ◽  
Infantile Autism ◽  
Serum Folate ◽  
Controlled Study ◽  
Autistic Children ◽  
Serotonin Turnover ◽  
The Brain

Background. Biomarkers such as oxidative stress, folate receptor alpha (FRα) autoimmunity, and abnormal brain serotonin turnover are common in autism. Methods. Oxidative stress biomarkers with pro- and antioxidants were measured in the severe form of infantile autism (n = 38) and controls (n = 24). Children and parents had repeated testing for serum FR autoantibodies, spinal fluid dopamine and serotonin metabolites, pterins, and N5-methyltetrahydrofolate (MTHF). Statistical analysis assessed correlations between variables. Genetic analysis included the SLC6A4 and SLC29A4 genes encoding synaptic serotonin reuptake proteins. Results. Compared to controls, the autism group showed a significant increase in oxidative DNA damage in lymphocytes, plasma ceruloplasmin and copper levels with a high copper/zinc ratio, thiol proteins, and superoxide dismutase (SOD) activity. Vitamin C levels were significantly diminished. In most autistic patients, the vitamin A (64%) and D (70%) levels were low. Serum FR autoantibodies fluctuating over 5–7 week periods presented in 68% of all autistic children, 41% of parents vs. 3.3% of control children and their parents. CSF showed lowered serotonin 5-hydroxyindole acetic acid (5HIAA) metabolites in 13 (34%), a low 5HIAA to HVA (dopamine metabolite) ratio in 5 (13%), low 5HIAA and MTHF in 2 (5%), and low MTHF in 8 patients (21%). A known SLC6A4 mutation was identified only in 1 autistic child with low CSF 5HIAA and a novel SLC29A4 mutation was identified in identical twins. Low CSF MTHF levels among only 26% of subjects can be explained by the fluctuating FR antibody titers. Two or more aberrant pro-oxidant and/or antioxidant factors predisposed to low CSF serotonin metabolites. Three autistic children having low CSF 5HIAA and elevated oxidative stress received antioxidative supplements followed by CSF 5HIAA normalisation. Conclusion. In autism, we found diverse combinations for FR autoimmunity and/or oxidative stress, both amenable to treatment. Parental and postnatal FR autoantibodies tend to block folate passage to the brain affecting folate-dependent pathways restored by folinic acid treatment, while an abnormal redox status tends to induce reduced serotonin turnover, corrected by antioxidant therapy. Trial Registration. The case-controlled study was approved in 2008 by the IRB at Liège University (Belgian Number: B70720083916). Lay Summary. Children with severe infantile autism frequently have serum folate receptor autoantibodies that block the transport of the essential vitamin folate across the blood-brain barrier to the brain. Parents are often asymptomatic carriers of these serum folate receptor autoantibodies, which in mothers can block folate passage across the placenta to their unborn child. This folate deficiency during the child’s intrauterine development may predispose to neural tube defects and autism. Oxidative stress represents a condition with the presence of elevated toxic oxygen derivatives attributed to an imbalance between the formation and protection against these toxic reactive oxygen derivatives. Oxidative stress was found to be present in autistic children where these reactive oxygen derivatives can cause damage to DNA, which changes DNA function and regulation of gene expression. In addition, excessive amounts of these toxic oxygen derivatives are likely to damage the enzyme producing the neuromessenger serotonin in the brain, diminished in about 1/3 of the autistic children. Testing children with autism for oxidative stress and its origin, as well as testing for serum folate receptor autoantibodies, could open new approaches towards more effective treatments.

scholarly journals The maternal effect in infantile autism: elevated DNA damage degree in patients and their mothers

2016 ◽  
Vol 62 (4) ◽  
pp. 466-470 ◽  
Author(s):  
L.N. Porokhovnik ◽  
S.V. Kostyuk ◽  
E.S. Ershova ◽  
S.M. Stukalov ◽  
N.N. Veiko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Maternal Effect ◽  
Infantile Autism ◽  
Reproductive Age ◽  
Control Group ◽  
Healthy Children ◽  
Tail Moment ◽  
Autistic Children ◽  
Comet Tail

Infantile autism is a common disorder of mental development, which is characterized by impairments in the communicative, cognitive and speech spheres and obsessional stereotyped behaviour. Although in most cases, pathogenic factors remain unclear, infantile autism has a significant hereditary component, however, its etiology is also under the influence of environmental factors, including the condition of the mother's body during pregnancy (“maternal effect”). Oxidative stress is assumed to play a key role in the pathogenesis of infantile autism. It is known that oxidative stress has a prominent genotoxic effect, which is realized through inducing single and double strand breaks of the nuclear DNA. We evaluated the degree of DNA damage in patients with infantile autism and their mothers using DNA comet assay. The comet tail moment and DNA per cent ratio in the tail were assessed for each individual. The two parameters appeared to be strongly correlated (r=0.90). Mean and median values of both parameters were considerably higher in the sample of autistic children, than in age-matching healthy controls. Interestingly, these parameters were also elevated in healthy mothers of autistic children, with no difference from the values in the group of autistic children. The control group of healthy women of reproductive age, who had no children with autism, differed by the DNA comet tail moment from the group of mothers of autistic children, but did not differ significantly from the control group of healthy children. The results suggest that there are genotoxic factors in mentally healthy mothers of autistic children, which can determine the pathological process in the foeti via environmental “maternal effect” during gestation.

scholarly journals Reactive Oxygen Species in Neurodegenerative Diseases: Implications in Pathogenesis and Treatment Strategies

2021 ◽  
Author(s):  
Johnson Olaleye Oladele ◽  
Adenike T. Oladiji ◽  
Oluwaseun Titilope Oladele ◽  
Oyedotun M. Oyeleke
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Protein Misfolding ◽  
Critical Role ◽  
Treatment Strategies ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
The Brain

Neurodegenerative diseases are debilitating disorders which compromise motor or cognitive functions and are rapidly becoming a global communal disorder with over 46.8 million people suffering dementia worldwide. Aetiological studies have showed that people who are exposed to agricultural, occupational and environmental toxic chemicals that can interfere and degenerate dopaminergic neurons are prone to developing neurodegenerative diseases such as Parkinson Disease. The complex pathogenesis of the neurodegenerative diseases remains largely unknown; however, mounting evidence suggests that oxidative stress, neuroinflammation, protein misfolding, and apoptosis are the hallmarks of the diseases. Reactive oxygen species (ROS) are chemically reactive molecules that have been implicated in the pathogenesis of neurodegenerative diseases. ROS play a critical role as high levels of oxidative stress are commonly observed in the brain of patients with neurodegenerative disorders. This chapter focus on the sources of ROS in the brain, its involvement in the pathogenesis of neurodegenerative diseases and possible ways to mitigate its damaging effects in the affected brain.

scholarly journals Resistance of nerve cells to oxidative injury

2011 ◽  
Vol 64 (7-8) ◽  
pp. 386-391 ◽  
Author(s):  
Zorica Jovanovic ◽  
Svetlana Jovanovic
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Hydrogen Peroxide ◽  
Neuronal Damage ◽  
Reactive Oxygen ◽  
Cell Types ◽  
Brain Cell ◽  
Nerve Cells ◽  
Oxygen Species ◽  
The Brain

Introduction. Reactive oxygen species are particularly active in the brain and neuronal tissue, and they are involved in numerous cellular functions, including cell death and survival. Brain and oxidative stress. A high metabolic rate and an abundant supply of the transition metals make the brain an ideal target for a free radical attack. In addition, the brain has a high susceptibility to oxidative stress due to the high lipid content and relatively lower regenerative capacity in comparison with other tissues. Vulnerability of nerve cells to oxidative stress. The neurons are more vulnerable to oxidative stress than other brain cell types. In addition to the two conventional enzymes, catalase and glutathione peroxidase, peroxiredoxins remove intracellular hydrogen peroxide by reducing it to water. The recent work increasingly supports the hypothesis that peroxiredoxins are not only antioxidant proteins, but they also play a role in cell signaling by controlling hydrogen peroxide and alkyl hydroperoxide levels. The accumulating evidence demonstrates that microglia can become deleterious and damage neurons. The overactivated microglia release reactive oxygen species that cause neuronal damage in neurodegenerative diseases. Conclusion. The defense of nerve cells against reactive oxygen species - mediated oxidative damage is essential for maintaining the functionality of nerve cells. The ongoing studies show that neuron-glial compartmentalization of antioxidants is critical for the neuronal signaling by hydrogen peroxide as well as the neuronal protection.

Direct Assessments of the Antioxidant Effects of Propofol Medium Chain Triglyceride/Long Chain Triglyceride on the Brain of Stroke-prone Spontaneously Hypertensive Rats Using Electron Spin Resonance Spectroscopy

2008 ◽  
Vol 109 (3) ◽  
pp. 426-435 ◽  
Author(s):  
Kyo Kobayashi ◽  
Fumihiko Yoshino ◽  
Shun-Suke Takahashi ◽  
Kazuo Todoki ◽  
Yojiro Maehata ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Electron Spin Resonance ◽  
Hydroxyl Radical ◽  
Electron Spin ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Spontaneously Hypertensive ◽  
Spin Resonance ◽  
The Brain

Background Antioxidant anesthetics such as propofol (2,6-diisopropylphenol) directly inhibit lipid peroxidation via the generation of reactive oxygen species. Currently, there are no other studies regarding the direct effects of propofol medium chain triglyceride/long chain triglyceride (MCT/LCT) on reactive oxygen species generation or in experimental models of reactive oxygen species-induced oxidative stress in the brain. Methods The authors investigated the effects of propofol MCT/LCT on reactive oxygen species (hydroxyl radical or superoxide) by electron spin resonance spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. The effects of propofol MCT/LCT on oxidative stress in the brain of Wistar-Kyoto rats or stroke-prone spontaneously hypertensive rats were investigated by using an in vivo L-band electron spin resonance system to monitor the decay rate of 3-methoxycarbonyl-2,2,5,5-tetramethyl-pyrrolidine-1-oxyl as a nitroxyl spin probe. Results These studies provided direct evidence that propofol MCT/LCT inhibited hydroxyl radical generation, but not superoxide generation. Regarding the hydroxyl radical from the Fenton system, it is likely to be due to the scavenging effects of vehicle. Anesthesia with propofol MCT/LCT reduced the degree of the high oxidative stress in the brain of stroke-prone spontaneously hypertensive rats. Conclusion The current data show that propofol, mixed with clinical reagents (propofol MCT/LCT), resulted in the down-regulation of high oxidative stress due to scavenging hydroxyl radical, as demonstrated by in vitro or in vivo electron spin resonance analysis. These results led to reduced levels of hydroxyl radical, formed by brain injury such as stroke, and may therefore provide advantages for neuroprotection during anesthesia for craniotomy, e.g., in cases of brain disease.

scholarly journals Mechanisms of neurodegeneration in Alzheimer’s disease

2012 ◽  
Vol 65 (7-8) ◽  
pp. 301-307 ◽  
Author(s):  
Zorica Jovanovic
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Microglial Activation ◽  
Reactive Oxygen ◽  
Amyloid Peptide ◽  
Oxygen Species ◽  
Disease Pathogenesis ◽  
The Brain

Introduction. Recent research into mechanisms of neurodegeneration in Alzheimer?s disease has lead to a dramatic increase in our understanding of the mechanisms of cell death and neuroprotection. Alzheimer?s disease is a complex disease with multiple etiological factors involved in disease pathogenesis. Oxidative stress and mitochondrial dysfunction in Alzheimer?s disease. Amyloid-? peptide toxicity is mediated at least in part by oxidative stress. Amyloid-? peptide directly generates reactive oxygen species in the presence of redox-active metal ions. In Alzheimer?s disease, oxidative stress is present early in pathogenesis and contributes to disease pathogenesis. Unlike other organs, the brain is especially vulnerable to reactive oxygen species due to neurons having relatively low levels of endogenous antioxidants. Overly abundant oxygen radicals cause the destruction of cellular macromolecules and participate in signaling mechanisms that result in apoptotic cell death. Microglial activation and nicotinamide adenine dinucleotide phosphate oxidase in Alzheimer?s disease. There is a wealth of evidence demonstrating that microglia, the resident innate immune cells in the brain, can become deleterious and damage neurons. Microglial activation causes neuron damage through the production of neurotoxic factors, such as reactive oxygen species and cytokines that are toxic to neurons. The neuron also has strong homeostatic mechanisms that can delay or prevent activation of apoptosis and necrosis. Insulin resistance and Alzheimer?s disease. Insulin plays a role in Alzheimer?s disease, as it is involved in the metabolism of ?-amyloid. Hyperinsulinemia and type-2 diabetes mellitus results in an increased risk of developing Alzheimer?s disease, but its implications when the disease is already well established remain unknown. Treatment of central insulin resistance may be a promising avenue, not only in metabolic syndrom, but also in Alzheimer?s disease. Conclusion. Increasing evidence suggests a role for oxidative stress, mitochondrial dysfunction, microglial activation and insulin resistance in pathogenesis of neurodegenerative diseases including Alzheimer?s disease.

Unfavourable Left-Right Asymmetries of the Brain and Autism: A Question of Methodology

1982 ◽  
Vol 140 (3) ◽  
pp. 312-319 ◽  
Author(s):  
Luke Tsai ◽  
Charles G. Jacoby ◽  
Mark A. Stewart ◽  
Jean M. Beisler
Keyword(s):  
Language Development ◽  
Neurological Disorders ◽  
Ct Scanning ◽  
Infantile Autism ◽  
Ct Scans ◽  
Autistic Children ◽  
Delayed Language Development ◽  
The Brain ◽  
Methodological Difficulties

SummaryThirty-six patients with infantile autism and various neurological disorders underwent computerized tomographic (CT) scanning of the brain. All CT scans were assessed blindly and independently by a diagnostic radiologist. Two techniques modified from two previous studies were used for measuring parieto-occipital asymmetry. The frequency of reversed asymmetry in autistic patients was the same as that in patients with various neurological disorders, and there was no significant association between reversed asymmetry and delayed language development. The study does not support the concept that unfavourable morphological asymmetries of the brain near the posterior language zone may contribute to the difficulties autistic children experience in acquiring language. Methodological difficulties and the design of new studies are discussed.

Catecholamines metabolism in infantile autism: A controlled study of 22 autistic children

1987 ◽  
Vol 17 (3) ◽  
pp. 333-347 ◽  
Author(s):  
Jean -Marie Launay ◽  
Claude Bursztejn ◽  
Pierre Ferrari ◽  
Claude Dreux ◽  
Alain Braconnier ◽  
...  
Keyword(s):  
Infantile Autism ◽  
Controlled Study ◽  
Autistic Children

Clinical aspects of reactive oxygen and nitrogen species

2004 ◽  
Vol 71 ◽  
pp. 121-133 ◽  
Author(s):  
Ascan Warnholtz ◽  
Maria Wendt ◽  
Michael August ◽  
Thomas Münzel
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Risk Factor ◽  
Endothelial Dysfunction ◽  
Vascular Tissue ◽  
Rapid Development ◽  
Reactive Oxygen ◽  
Clinical Aspects ◽  
No Production ◽  
Oxygen Species

Endothelial dysfunction in the setting of cardiovascular risk factors, such as hypercholesterolaemia, hypertension, diabetes mellitus and chronic smoking, as well as in the setting of heart failure, has been shown to be at least partly dependent on the production of reactive oxygen species in endothelial and/or smooth muscle cells and the adventitia, and the subsequent decrease in vascular bioavailability of NO. Superoxide-producing enzymes involved in increased oxidative stress within vascular tissue include NAD(P)H-oxidase, xanthine oxidase and endothelial nitric oxide synthase in an uncoupled state. Recent studies indicate that endothelial dysfunction of peripheral and coronary resistance and conductance vessels represents a strong and independent risk factor for future cardiovascular events. Ways to reduce endothelial dysfunction include risk-factor modification and treatment with substances that have been shown to reduce oxidative stress and, simultaneously, to stimulate endothelial NO production, such as inhibitors of angiotensin-converting enzyme or the statins. In contrast, in conditions where increased production of reactive oxygen species, such as superoxide, in vascular tissue is established, treatment with NO, e.g. via administration of nitroglycerin, results in a rapid development of endothelial dysfunction, which may worsen the prognosis in patients with established coronary artery disease.

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