Cargando…
Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology
Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation....
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727757/ https://www.ncbi.nlm.nih.gov/pubmed/35002805 http://dx.doi.org/10.3389/fpsyt.2021.788779 |
_version_ | 1784626589849354240 |
---|---|
author | Harutyunyan, Aida A. Harutyunyan, Hayk A. Yenkoyan, Konstantin B. |
author_facet | Harutyunyan, Aida A. Harutyunyan, Hayk A. Yenkoyan, Konstantin B. |
author_sort | Harutyunyan, Aida A. |
collection | PubMed |
description | Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation. The latter might be considered as one of the factors damaging neuronal cells. Several cell types trigger and sustain such neuroinflammation. In this study, we traced different markers of immune system activation on both cellular (immune cell phenotypes) and mediatory levels (production of cytokines) alongside adverse hematology and biochemistry screening in a group of autistic children. In addition, we analyzed the main metabolic pathways potentially involved in ASD development: energy (citric acid cycle components), porphyrin, and neurotransmitter metabolism. Several ASD etiological factors, like heavy metal intoxication, and risk factors—genetic polymorphisms of the relevant neurotransmitters and vitamin D receptors—were also analyzed. Finally, broad linear regression analysis allowed us to elucidate the possible scenario that led to the development of chronic inflammation in ASD patients. Obtained data showed elevated levels of urinary cis-aconitate, isocitrate, alfa-ketoglutarate, and HMG. There were no changes in levels of metabolites of monoamine neurotransmitters, however, the liver-specific tryptophan kinurenine pathway metabolites showed increased levels of quinolinate (QUIN) and picolinate, whereas the level of kynurenate remained unchanged. Abovementioned data demonstrate the infringement in energy metabolism. We found elevated levels of lead in red blood cells, as well as altered porphyrin metabolism, which support the etiological role of heavy metal intoxication in ASD. Lead intoxication, the effect of which is intensified by a mutation of the VDR-Taq and MAO-A, leads to quinolinic acid increase, resulting in energy metabolism depletion and mitochondrial dysfunction. Moreover, our data backing the CD4+CD3+ T-cell dependence of mitochondrial dysfunction development in ASD patients reported in our previous study leads us to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients. |
format | Online Article Text |
id | pubmed-8727757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87277572022-01-06 Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology Harutyunyan, Aida A. Harutyunyan, Hayk A. Yenkoyan, Konstantin B. Front Psychiatry Psychiatry Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and restricted-repetitive patterns of behavior, interests, or activities. ASD is generally associated with chronic inflammatory states, which are linked to immune system dysfunction and/or hyperactivation. The latter might be considered as one of the factors damaging neuronal cells. Several cell types trigger and sustain such neuroinflammation. In this study, we traced different markers of immune system activation on both cellular (immune cell phenotypes) and mediatory levels (production of cytokines) alongside adverse hematology and biochemistry screening in a group of autistic children. In addition, we analyzed the main metabolic pathways potentially involved in ASD development: energy (citric acid cycle components), porphyrin, and neurotransmitter metabolism. Several ASD etiological factors, like heavy metal intoxication, and risk factors—genetic polymorphisms of the relevant neurotransmitters and vitamin D receptors—were also analyzed. Finally, broad linear regression analysis allowed us to elucidate the possible scenario that led to the development of chronic inflammation in ASD patients. Obtained data showed elevated levels of urinary cis-aconitate, isocitrate, alfa-ketoglutarate, and HMG. There were no changes in levels of metabolites of monoamine neurotransmitters, however, the liver-specific tryptophan kinurenine pathway metabolites showed increased levels of quinolinate (QUIN) and picolinate, whereas the level of kynurenate remained unchanged. Abovementioned data demonstrate the infringement in energy metabolism. We found elevated levels of lead in red blood cells, as well as altered porphyrin metabolism, which support the etiological role of heavy metal intoxication in ASD. Lead intoxication, the effect of which is intensified by a mutation of the VDR-Taq and MAO-A, leads to quinolinic acid increase, resulting in energy metabolism depletion and mitochondrial dysfunction. Moreover, our data backing the CD4+CD3+ T-cell dependence of mitochondrial dysfunction development in ASD patients reported in our previous study leads us to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients. Frontiers Media S.A. 2021-12-22 /pmc/articles/PMC8727757/ /pubmed/35002805 http://dx.doi.org/10.3389/fpsyt.2021.788779 Text en Copyright © 2021 Harutyunyan, Harutyunyan and Yenkoyan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Psychiatry Harutyunyan, Aida A. Harutyunyan, Hayk A. Yenkoyan, Konstantin B. Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title | Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title_full | Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title_fullStr | Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title_full_unstemmed | Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title_short | Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology |
title_sort | novel probable glance at inflammatory scenario development in autistic pathology |
topic | Psychiatry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727757/ https://www.ncbi.nlm.nih.gov/pubmed/35002805 http://dx.doi.org/10.3389/fpsyt.2021.788779 |
work_keys_str_mv | AT harutyunyanaidaa novelprobableglanceatinflammatoryscenariodevelopmentinautisticpathology AT harutyunyanhayka novelprobableglanceatinflammatoryscenariodevelopmentinautisticpathology AT yenkoyankonstantinb novelprobableglanceatinflammatoryscenariodevelopmentinautisticpathology |