Redox Regulation and the Autistic Spectrum: Role of Tryptophan Catabolites, Immuno-inflammation, Autoimmunity and the Amygdala

Anderson, Geoffrey M.; Maes, Michaël

doi:10.2174/1570159x11666131120223757

Cited by 28 publications

(26 citation statements)

References 279 publications

(326 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it has been speculated that this could be linked to stress regulation together with 5-HT and cortisol [48]. Future studies should explore the pathophysiology of ADS while paying more attention to the different ASD subtypes.…”

Section: Discussionmentioning

confidence: 99%

Kynurenine Pathway in Autism Spectrum Disorders in Children

et al. 2017

View full text Add to dashboard Cite

Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

show abstract

Section: Discussionmentioning

confidence: 99%

Kynurenine Pathway in Autism Spectrum Disorders in Children

et al. 2017

View full text Add to dashboard Cite

show abstract

“…However, there is evidence that increased intestinal permeability or apoptosis of intestinal epithelial cells may allow for increased SCFA levels in the systemic circulation and consequently the CNS [264,265]. In any event, SCFAs are unlikely to be the only metabolites ultimately derived from the microbiota involved in the pathogenesis of these illnesses, as abnormal TRYCAT levels are also implicated [266].…”

Section: Potential Mechanistic Explanations For Propionic Acid-inducementioning

confidence: 99%

The Role of the Microbial Metabolites Including Tryptophan Catabolites and Short Chain Fatty Acids in the Pathophysiology of Immune-Inflammatory and Neuroimmune Disease

Morris¹,

et al. 2016

Self Cite

View full text Add to dashboard Cite

There is a growing awareness that gut commensal metabolites play a major role in host physiology and indeed the pathophysiology of several illnesses. The composition of the microbiota largely determines the levels of tryptophan in the systemic circulation and hence, indirectly, the levels of serotonin in the brain. Some microbiota synthesize neurotransmitters directly, e.g., gamma-amino butyric acid, while modulating the synthesis of neurotransmitters, such as dopamine and norepinephrine, and brain-derived neurotropic factor (BDNF). The composition of the microbiota determines the levels and nature of tryptophan catabolites (TRYCATs) which in turn has profound effects on aryl hydrocarbon receptors, thereby influencing epithelial barrier integrity and the presence of an inflammatory or tolerogenic environment in the intestine and beyond. The composition of the microbiota also determines the levels and ratios of short chain fatty acids (SCFAs) such as butyrate and propionate. Butyrate is a key energy source for colonocytes. Dysbiosis leading to reduced levels of SCFAs, notably butyrate, therefore may have adverse effects on epithelial barrier integrity, energy homeostasis, and the T helper 17/regulatory/T cell balance. Moreover, dysbiosis leading to reduced butyrate levels may increase bacterial translocation into the systemic circulation. As examples, we describe the role of microbial metabolites in the pathophysiology of diabetes type 2 and autism.

show abstract

“…Chronic activation of the TRYCAT pathway leads to production of several neuroactive, neuroprotective and neurotoxic TRYCATs. For example, QA acts as potent neurotoxin, which inhibits ATP production by mitochondria, activates nitro-oxidative stress pathways, disrupts neuron glial communication and blood brain barrier integrity, induces apoptosis of glial cells, and directly damages neurons and function through its agonistic activity at N-methyl D-aspartate (NMDA) receptors (NMDAr) (31). KA, on the other hand, functions as an antagonist of NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors thereby acting to regulate levels of glutamate and dopamine, and binds to the alpha-7-nicotinamide acetylcholine receptor (31).…”

Section: Introductionmentioning

confidence: 99%

“…For example, QA acts as potent neurotoxin, which inhibits ATP production by mitochondria, activates nitro-oxidative stress pathways, disrupts neuron glial communication and blood brain barrier integrity, induces apoptosis of glial cells, and directly damages neurons and function through its agonistic activity at N-methyl D-aspartate (NMDA) receptors (NMDAr) (31). KA, on the other hand, functions as an antagonist of NMDA, amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate receptors thereby acting to regulate levels of glutamate and dopamine, and binds to the alpha-7-nicotinamide acetylcholine receptor (31). An activated TRYCAT pathway is a feature of a number of medical conditions characterized by immune activation and chronic inflammation (32)(33)(34), as well as neuro-psychiatric diseases including Parkinson's disease (35)(36)(37), multiple sclerosis (38,39), stroke (40)(41)(42)(43), somatiform disorders (44), schizophrenia (45), psychosis (46) and Alzheimer's disease (47,48).…”

Section: Introductionmentioning

confidence: 99%