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Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway

1
Department of Woman and Child, Neuropsychiatry for Child and Adolescent Unit, General Hospital “Riuniti” of Foggia, 71122 Foggia, Italy
2
Department of Mental Health, Physical and Preventive Medicine, Clinic of Child and Adolescent Neuropsychiatry, Università degli Studi della Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
3
Department of the Sciences of Agriculture, Food and Environment, University of Foggia, Via Napoli 25, 71100 Foggia, Italy
4
Department of Education Sciences, Psychology and Communication, University of Bari, 70121 Bari, Italy
5
Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto, 71122 Foggia, Italy
6
Department of Clinical and Experimental Medicine, University of Foggia, 71122 Foggia, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Brain Sci. 2020, 10(9), 631; https://doi.org/10.3390/brainsci10090631
Received: 17 July 2020 / Revised: 31 August 2020 / Accepted: 10 September 2020 / Published: 11 September 2020
Autism Spectrum Disorder (ASD) etiopathogenesis is still unclear and no effective preventive and treatment measures have been identified. Research has focused on the potential role of neuroinflammation and the Kynurenine pathway; here we review the nature of these interactions. Pre-natal or neonatal infections would induce microglial activation, with secondary consequences on behavior, cognition and neurotransmitter networks. Peripherally, higher levels of pro-inflammatory cytokines and anti-brain antibodies have been identified. Increased frequency of autoimmune diseases, allergies, and recurring infections have been demonstrated both in autistic patients and in their relatives. Genetic studies have also identified some important polymorphisms in chromosome loci related to the human leukocyte antigen (HLA) system. The persistence of immune-inflammatory deregulation would lead to mitochondrial dysfunction and oxidative stress, creating a self-sustaining cytotoxic loop. Chronic inflammation activates the Kynurenine pathway with an increase in neurotoxic metabolites and excitotoxicity, causing long-term changes in the glutamatergic system, trophic support and synaptic function. Furthermore, overactivation of the Kynurenine branch induces depletion of melatonin and serotonin, worsening ASD symptoms. Thus, in genetically predisposed subjects, aberrant neurodevelopment may derive from a complex interplay between inflammatory processes, mitochondrial dysfunction, oxidative stress and Kynurenine pathway overexpression. To validate this hypothesis a new translational research approach is necessary. View Full-Text
Keywords: autism spectrum disorder; neuroinflammation; Kynurenine pathway; microglia; oxidative stress; mitochondrial disorder; immune deregulation; QUIN (quinolinic acid); KYNA (kynurenic acid); tryptophan catabolites autism spectrum disorder; neuroinflammation; Kynurenine pathway; microglia; oxidative stress; mitochondrial disorder; immune deregulation; QUIN (quinolinic acid); KYNA (kynurenic acid); tryptophan catabolites
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MDPI and ACS Style

Savino, R.; Carotenuto, M.; Polito, A.N.; Di Noia, S.; Albenzio, M.; Scarinci, A.; Ambrosi, A.; Sessa, F.; Tartaglia, N.; Messina, G. Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway. Brain Sci. 2020, 10, 631. https://doi.org/10.3390/brainsci10090631

AMA Style

Savino R, Carotenuto M, Polito AN, Di Noia S, Albenzio M, Scarinci A, Ambrosi A, Sessa F, Tartaglia N, Messina G. Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway. Brain Sciences. 2020; 10(9):631. https://doi.org/10.3390/brainsci10090631

Chicago/Turabian Style

Savino, Rosa, Marco Carotenuto, Anna N. Polito, Sofia Di Noia, Marzia Albenzio, Alessia Scarinci, Antonio Ambrosi, Francesco Sessa, Nicola Tartaglia, and Giovanni Messina. 2020. "Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From Neuroinflammation to the Kynurenine Pathway" Brain Sciences 10, no. 9: 631. https://doi.org/10.3390/brainsci10090631

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