Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism

Pastural, Élodie; Ritchie, Stephen M.; Lu, Yingshen; Jin, Wei; Kavianpour, Amir; Su-Myat, Khine Khine; Heath, Doug; Wood, Paul L.; Fisk, Maura; Goodenowe, Dayan B.

doi:10.1016/j.plefa.2009.06.003

Cited by 89 publications

(123 citation statements)

References 82 publications

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“…Carnitine is reduced in ASD children (Mostafa, 2005). In contrast, long-chain and very long-chain fatty acids and acyl-carnitine are increased in these patients (Pastural et al, 2009;. Similar metabolite changes are evident in animal models of ASD treated with PPA and butyrate (Thomas et al, 2010(Thomas et al, , 2012.…”

Section: Potential Mechanism Microbiota Alterations Lead To Asd and Rmentioning

confidence: 62%

Microbiome Disturbances and Autism Spectrum Disorders

2015

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Autism spectrum disorders (ASDs) are considered a heterogenous set of neurobehavioral diseases, with the rates of diagnosis dramatically increasing in the past few decades. As genetics alone does not explain the underlying cause in many cases, attention has turned to environmental factors as potential etiological agents. Gastrointestinal disorders are a common comorbidity in ASD patients. It was thus hypothesized that a gut-brain link may account for some autistic cases. With the characterization of the human microbiome, this concept has been expanded to include the microbiota-gut-brain axis. There are mounting reports in animal models and human epidemiologic studies linking disruptive alterations in the gut microbiota or dysbiosis and ASD symptomology. In this review, we will explore the current evidence that gut dysbiosis in animal models and ASD patients correlates with disease risk and severity. The studies to date have surveyed how gut microbiome changes may affect these neurobehavioral disorders. However, we harbor other microbiomes in the body that might impact brain function. We will consider microbial colonies residing in the oral cavity, vagina, and the most recently discovered one in the placenta. Based on the premise that gut microbiota alterations may be causative agents in ASD, several therapeutic options have been tested, such as diet modulations, prebiotics, probiotics, synbiotics, postbiotics, antibiotics, fecal transplantation, and activated charcoal. The potential benefits of these therapies will be considered. Finally, the possible mechanisms by which changes in the gut bacterial communities may result in ASD and related neurobehavioral disorders will be examined.

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Section: Potential Mechanism Microbiota Alterations Lead To Asd and Rmentioning

confidence: 62%

Microbiome Disturbances and Autism Spectrum Disorders

2015

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“…In addition, lipid peroxidation, a down-stream effect of reduced ROS deactivation, is increased in autistic children [14,15]. Extra-mitochondrial processing of palmitate, the key energy source for mitochondria, was observed to be universally increased in ASD [2]. Subjects with definite mitochondrial disease (according to the criteria defined by [16]) have a higher occurrence of autism than expected by chance in the average population [1], especially of regressive autism [17].…”

Section: Overview Of Mitochondrial Dysfunction In Asdmentioning

confidence: 99%

“…Mitochondrial dysfunction in autism has been implicated by several research groups [1][2][3]. Elevated plasma lactate, a commonly used indicator of mitochondrial dysfunction, has been observed to present in 20 [4] to 40 percent of ASD subjects [5].…”

Section: Overview Of Mitochondrial Dysfunction In Asdmentioning

confidence: 99%

“…The activity of the mitochondrial electron transport chain (ETC), complexes I and III, has been reported to be decreased [7][8][9]. Glutathione, the key intramitochondrial reactive oxygen species (ROS) neutralizer, is decreased in ASD [2,[10][11][12][13]. In addition, lipid peroxidation, a down-stream effect of reduced ROS deactivation, is increased in autistic children [14,15].…”

Section: Overview Of Mitochondrial Dysfunction In Asdmentioning

confidence: 99%

“…The principal mechanism of detoxifying peroxide is via glutathione. The oxidation of GSH is one of the first toxic metabolic consequences of glutamate toxicity in neurons [69], and decreased GSH is a common observation in autism [2,[11][12][13]109]. Unlike neurons, which have metabolic mechanisms that enable it to rapidly cycle glutamate, astrocytes must process the aspartate and glutamate they import.…”

Section: Glutamate Transport and Intracellular Metabolism In Purkinjementioning

confidence: 99%

See 2 more Smart Citations

The Biochemical Basis of Autistic Behavior and Pathology

Goodenowe¹,

Pastural²

2011

Autism - A Neurodevelopmental Journey From Genes to Behaviour

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Biochemical Biomarkers for Autism Spectrum Disorder

Anderson

2014

Handbook of Autism and Pervasive Developmental Disorders, Fourth Edition

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Biochemical biomarker studies of ASD individuals have been undertaken in order to identify biochemical alterations that might advance the understanding of the atypical neurodevelopment seen in ASD. In addition, there is the promise that biochemical biomarkers might be useful in predicting risk and in subtyping. Most of the studies to date have examined neurochemical biomarkers related to neural transmission in the central and peripheral nervous systems. We first deal with neurochemical studies measuring levels of neurotransmitters, their metabolites, and associated enzymes in blood, urine, and cerebrospinal fluid (CSF). Separate sections cover serotonin, dopamine, and stress response systems (including the central noradrenergic, sympathoadrenomedullary, and hypothalamic‐pituitary‐adrenal axis systems). Following sections review research on melatonin, sex hormones, neuropeptides including oxytocin, amino acids and acetylcholine, purines and related compounds, immune‐related measures, oxidative stress/redox status, and “omics” research.

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Novel plasma phospholipid biomarkers of autism: Mitochondrial dysfunction as a putative causative mechanism

Cited by 89 publications

References 82 publications

Microbiome Disturbances and Autism Spectrum Disorders

Microbiome Disturbances and Autism Spectrum Disorders

The Biochemical Basis of Autistic Behavior and Pathology

Biochemical Biomarkers for Autism Spectrum Disorder

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