PMID- 32932826
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201028
IS  - 2076-3425 (Print)
IS  - 2076-3425 (Electronic)
IS  - 2076-3425 (Linking)
VI  - 10
IP  - 9
DP  - 2020 Sep 11
TI  - Analyzing the Potential Biological Determinants of Autism Spectrum Disorder: From 
      Neuroinflammation to the Kynurenine Pathway.
LID - 10.3390/brainsci10090631 [doi]
LID - 631
AB  - 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.
FAU - Savino, Rosa
AU  - Savino R
AD  - Department of Woman and Child, Neuropsychiatry for Child and Adolescent Unit, 
      General Hospital "Riuniti" of Foggia, 71122 Foggia, Italy.
FAU - Carotenuto, Marco
AU  - Carotenuto M
AUID- ORCID: 0000-0002-8136-7597
AD  - Department of Mental Health, Physical and Preventive Medicine, Clinic of Child 
      and Adolescent Neuropsychiatry, Universita degli Studi della Campania "Luigi 
      Vanvitelli", 81100 Caserta, Italy.
FAU - Polito, Anna Nunzia
AU  - Polito AN
AD  - Department of Woman and Child, Neuropsychiatry for Child and Adolescent Unit, 
      General Hospital "Riuniti" of Foggia, 71122 Foggia, Italy.
FAU - Di Noia, Sofia
AU  - Di Noia S
AD  - Department of Woman and Child, Neuropsychiatry for Child and Adolescent Unit, 
      General Hospital "Riuniti" of Foggia, 71122 Foggia, Italy.
FAU - Albenzio, Marzia
AU  - Albenzio M
AD  - Department of the Sciences of Agriculture, Food and Environment, University of 
      Foggia, Via Napoli 25, 71100 Foggia, Italy.
FAU - Scarinci, Alessia
AU  - Scarinci A
AD  - Department of Education Sciences, Psychology and Communication, University of 
      Bari, 70121 Bari, Italy.
FAU - Ambrosi, Antonio
AU  - Ambrosi A
AD  - Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto, 
      71122 Foggia, Italy.
FAU - Sessa, Francesco
AU  - Sessa F
AUID- ORCID: 0000-0003-0357-8791
AD  - Department of Clinical and Experimental Medicine, University of Foggia, 71122 
      Foggia, Italy.
FAU - Tartaglia, Nicola
AU  - Tartaglia N
AUID- ORCID: 0000-0001-6845-7080
AD  - Department of Medical and Surgical Sciences, University of Foggia, Viale Pinto, 
      71122 Foggia, Italy.
FAU - Messina, Giovanni
AU  - Messina G
AUID- ORCID: 0000-0002-0011-867X
AD  - Department of Clinical and Experimental Medicine, University of Foggia, 71122 
      Foggia, Italy.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200911
PL  - Switzerland
TA  - Brain Sci
JT  - Brain sciences
JID - 101598646
PMC - PMC7563403
OTO - NOTNLM
OT  - KYNA (kynurenic acid)
OT  - Kynurenine pathway
OT  - QUIN (quinolinic acid)
OT  - autism spectrum disorder
OT  - immune deregulation
OT  - microglia
OT  - mitochondrial disorder
OT  - neuroinflammation
OT  - oxidative stress
OT  - tryptophan catabolites
COIS- The authors declare that they have no competing interests.
EDAT- 2020/09/17 06:00
MHDA- 2020/09/17 06:01
PMCR- 2020/09/01
CRDT- 2020/09/16 01:01
PHST- 2020/07/17 00:00 [received]
PHST- 2020/08/31 00:00 [revised]
PHST- 2020/09/10 00:00 [accepted]
PHST- 2020/09/16 01:01 [entrez]
PHST- 2020/09/17 06:00 [pubmed]
PHST- 2020/09/17 06:01 [medline]
PHST- 2020/09/01 00:00 [pmc-release]
AID - brainsci10090631 [pii]
AID - brainsci-10-00631 [pii]
AID - 10.3390/brainsci10090631 [doi]
PST - epublish
SO  - Brain Sci. 2020 Sep 11;10(9):631. doi: 10.3390/brainsci10090631.