scholarly journals Novel Probable Glance at Inflammatory Scenario Development in Autistic Pathology

2021 ◽  
Vol 12 ◽  
Author(s):  
Aida A. Harutyunyan ◽  
Hayk A. Harutyunyan ◽  
Konstantin B. Yenkoyan
Keyword(s):  
Heavy Metal ◽  
Immune System ◽  
Energy Metabolism ◽  
Mitochondrial Dysfunction ◽  
Linear Regression Analysis ◽  
Autism Spectrum ◽  
Vitamin D Receptors ◽  
Immune System Dysfunction ◽  
Immune System Activation ◽  
Heavy Metal Intoxication

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.

scholarly journals Lead Induced, VDR Taq and MAO-A Associated Energy Metabolism Reduction, and CD4+CD3+ Lymphocytes-Dependent Inflammation as Main Pathogenetic Events in Autism Spectrum Disorders

2021 ◽  
Author(s):  
Aida A Harutyunyan ◽  
Hayk A Harutyunyan ◽  
Konstantin B Yenkoyan
Keyword(s):  
Autism Spectrum Disorders ◽  
Immune System ◽  
T Cell ◽  
Mitochondrial Dysfunction ◽  
Chronic Inflammation ◽  
Autism Spectrum ◽  
Autistic Children ◽  
Immune System Activation ◽  
System Activation ◽  
Spectrum Disorders

Abstract Background Autism Spectrum Disorder (ASD) is characterized by persistent deficits in social communication and interaction 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. Methods 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 (Krebs 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. Results Our data strongly support the lead induced, VDR Taq and MAO-A associated mitochondrial dysfunction, and CD4 + CD3 + T-cell dependent immune system activation and chronic inflammation as the key pathogenetic events in autism spectrum disorders. Moreover, our data supports the CD4 + CD3 + T-cell dependence of mitochondrial dysfunction development in ASD patient reported in our previous study. Limitations Difficulties to obtain target biological material (in this case cerebrospinal fluid, CSF) from autistic children under the age of 6 years and the small population of such patients limited our data from the qualitative and quantitative points of view. Nevertheless, the huge range of complex and target measurements has done partially overlap this flaw. Conclusions We come to the conclusion that redox-immune cross-talk is considered a main functional cell damaging factor in ASD patients.

Immunological Comparison of Pregnant Dahl Salt-Sensitive and Sprague Dawley Rats Commonly Used to Model Characteristics of Preeclampsia

2021 ◽  
Author(s):  
Erin B Taylor ◽  
Eric M George ◽  
Michael J. Ryan ◽  
Michael R Garrett ◽  
Jennifer M. Sasser
Keyword(s):  
T Cells ◽  
Immune System ◽  
Cell Activity ◽  
Late Pregnancy ◽  
Sprague Dawley ◽  
Clinical Model ◽  
Immune System Dysfunction ◽  
Immune System Activation ◽  
Sd Rats ◽  
Uterine Perfusion

The pregnant Dahl salt-sensitive (S) rat is an established pre-clinical model of superimposed spontaneous preeclampsia characterized by exacerbated hypertension, increased urinary protein excretion, and increased fetal demise. Because of the underlying immune system dysfunction present in preeclamptic pregnancies in humans, we hypothesized that the pregnant Dahl S rat would also have an altered immune status. Immune system activation was assessed during late pregnancy in the Dahl S model and compared to healthy pregnant Sprague Dawley (SD) rats subjected to either a sham procedure or a procedure to reduce uterine perfusion pressure (RUPP). Circulating immunoglobulin and cytokine levels were measured by ELISA and Milliplex bead assay, respectively, and percentages of circulating, splenic, and placental immune cells were determined using flow cytometry. The pregnant Dahl S rat exhibited an increase in CD4+ T cells, and specifically TNFα+CD4+ T cells, in the spleen compared to virgin Dahl S rats. The Dahl also had increased neutrophils and decreased B cells in the peripheral blood as compared to Dahl-virgin rats. SD rats that received the RUPP procedure had increases in circulating monocytes and increased IFN-ɣ+CD4+ splenic T cells. Together these findings suggest that dysregulated T cell activity are important factors in both the pregnant Dahl S rats and SD rats after the RUPP procedure.

scholarly journals Oxidative Stress and Immune System Dysfunction in Autism Spectrum Disorders

2020 ◽  
Vol 21 (9) ◽  
pp. 3293 ◽  
Author(s):  
Luca Pangrazzi ◽  
Luigi Balasco ◽  
Yuri Bozzi
Keyword(s):  
Oxidative Stress ◽  
Autism Spectrum Disorders ◽  
Immune System ◽  
Neural Development ◽  
Drug Targets ◽  
Autism Spectrum ◽  
Ros Scavenging ◽  
Novel Treatments ◽  
Immune System Dysfunction ◽  
Spectrum Disorders

Autism Spectrum Disorders (ASDs) represent a group of neurodevelopmental disorders associated with social and behavioral impairments. Although dysfunctions in several signaling pathways have been associated with ASDs, very few molecules have been identified as potentially effective drug targets in the clinic. Classically, research in the ASD field has focused on the characterization of pathways involved in neural development and synaptic plasticity, which support the pathogenesis of this group of diseases. More recently, immune system dysfunctions have been observed in ASD. In addition, high levels of reactive oxygen species (ROS), which cause oxidative stress, are present in ASD patients. In this review, we will describe the major alterations in the expression of genes coding for enzymes involved in the ROS scavenging system, in both ASD patients and ASD mouse models. In addition, we will discuss, in the context of the most recent literature, the possibility that oxidative stress, inflammation and immune system dysfunction may be connected to, and altogether support, the pathogenesis and/or severity of ASD. Finally, we will discuss the possibility of novel treatments aimed at counteracting the interplay between ROS and inflammation in people with ASD.

Comparing the Genetic Detox Ability and Heavy Metal Burden in a Cohort of Samples of Egyptian Children and those with Autistic Spectrum Disorder

2019 ◽  
Author(s):  
Blaurock-Busch E
Keyword(s):  
Heavy Metal ◽  
Autism Spectrum ◽  
Control Group ◽  
Potentially Toxic Metals ◽  
Gstt1 Null Genotype ◽  
Egyptian Children ◽  
Glutathione S Transferases ◽  
Metal Burden ◽  
Detoxification Pathway

The heavy metal burden of patients with Autism spectrum disorders (ASD) has been widely discussed [1-5]. Present knowledge suggests that ASD patients, compared to ‘normal’s’ show a greater metal burden, which may be a cause of the ASD pathogenesis, possibly due to a limited detoxification potential. We thus aimed to evaluate if the metal burden of ASD children is due to comprised detoxification ability, and if missing of enzymes such as the glutathione-S-transferases provide an explanation, or if additional factors play a role. Genetically, we noticed a slight difference in the detoxification ability of the ASD group compared to the Control group. In the ASD group, carrier of the genotype GSTT1 null genotype (i.e. the homozygous loss) are 1.7 times more common as in the Control group and the GSTT1 allele is more frequent in the ASD patient collective. These findings are not statistically significant but indicate a trend. In addition, our data indicates that levels of potentially toxic metals in blood and hair of both groups demonstrate a similar immediate and long-term exposure. However, 36% of the ASD group showed signs of zinc deficiency compared to 11% of the Control group and this points towards inefficiency of the Phase I detoxification pathway. More research is needed to explore the role of other elements in the detoxification pathway.

Microbiota, Immune System and Autism Spectrum Disorders: An Integrative Model towards Novel Treatment Options

2020 ◽  
Vol 27 (31) ◽  
pp. 5119-5136 ◽  
Author(s):  
Barbara Carpita ◽  
Donatella Marazziti ◽  
Lionella Palego ◽  
Gino Giannaccini ◽  
Laura Betti ◽  
...  
Keyword(s):  
Immune System ◽  
Familial Aggregation ◽  
Treatment Options ◽  
Autism Spectrum ◽  
Integrative Model ◽  
Neural Basis ◽  
Integrative Framework ◽  
Intermediate Phenotypes ◽  
Close Relatives

Background: Autism Spectrum Disorder (ASD) is a condition strongly associated with genetic predisposition and familial aggregation. Among ASD patients, different levels of symptoms severity are detectable, while the presence of intermediate autism phenotypes in close relatives of ASD probands is also known in literature. Recently, increasing attention has been paid to environmental factors that might play a role in modulating the relationship between genomic risk and development and severity of ASD. Within this framework, an increasing body of evidence has stressed a possible role of both gut microbiota and inflammation in the pathophysiology of neurodevelopment. The aim of this paper is to review findings about the link between microbiota dysbiosis, inflammation and ASD. Methods: Articles ranging from 1990 to 2018 were identified on PUBMED and Google Scholar databases, with keyword combinations as: microbiota, immune system, inflammation, ASD, autism, broad autism phenotype, adult. Results: Recent evidence suggests that microbiota alterations, immune system and neurodevelopment may be deeply intertwined, shaping each other during early life. However, results from both animal models and human samples are still heterogeneous, while few studies focused on adult patients and ASD intermediate phenotypes. Conclusion: A better understanding of these pathways, within an integrative framework between central and peripheral systems, might not only shed more light on neural basis of ASD symptoms, clarifying brain pathophysiology, but it may also allow to develop new therapeutic strategies for these disorders, still poorly responsive to available treatments.

scholarly journals Balloon cells promote immune system activation in focal cortical dysplasia type 2B

2021 ◽  
Author(s):  
Till S. Zimmer ◽  
Diede W.M. Broekaart ◽  
Mark Luinenburg ◽  
Caroline Mijnsbergen ◽  
Jasper J. Anink ◽  
...  
Keyword(s):  
Immune System ◽  
Focal Cortical Dysplasia ◽  
Cortical Dysplasia ◽  
Balloon Cells ◽  
Immune System Activation ◽  
System Activation

scholarly journals The Relationships between HIV-1 Infection, History of Methamphetamine Use Disorder, and Soluble Biomarkers in Blood and Cerebrospinal Fluid

Viruses ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1287
Author(s):  
T. Walter ◽  
Jennifer Iudicello ◽  
Debra Cookson ◽  
Donald Franklin ◽  
Bin Tang ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Immune System ◽  
Public Health Problem ◽  
Control Group ◽  
Csf Biomarkers ◽  
Immune System Dysfunction ◽  
Immune Biomarkers ◽  
Plasma Factor ◽  
History Of ◽  
Hiv 1

Methamphetamine (METH) use disorder is highly prevalent among people with HIV (PWH) and is a significant public health problem. HIV and METH use are each associated with immune system dysfunction; however, the combined effects on the immune system are poorly understood. This cross-sectional project measured soluble immune biomarkers in plasma and cerebrospinal fluid (CSF) collected from a control group, people with a history of a METH use disorder (METH+), PWH with no history of METH use disorder (HIV+), and PWH with a history of METH use disorder (HIV+/METH+). HIV, METH, and immune dysfunction can also be associated with affective and cognitive deficits, so we characterized mood and cognition in our participants. Two factor analyses were performed for the plasma and CSF biomarkers. Plasma IL-8, Ccl2, VEGF, and 8-isoprostane loaded onto one factor that was highest in the HIV+/METH+ group (p < 0.047) reflecting worse inflammation, vascular injury, and oxidative stress. This plasma factor was also negatively correlated with delayed recall (R = −0.49, p = 0.010), which was worst in the HIV+/METH+ group (p = 0.030 compared to the control group). Overall, these data implicate that combined HIV-1 infection and METH use may exacerbate inflammation, leading to worse cognition.

scholarly journals New Insights on the Role of TRP Channels in Calcium Signalling and Immunomodulation: Review of Pathways and Implications for Clinical Practice

2021 ◽  
Author(s):  
Saied Froghi ◽  
Charlotte R. Grant ◽  
Radhika Tandon ◽  
Alberto Quaglia ◽  
Brian Davidson ◽  
...  
Keyword(s):  
Immune System ◽  
Calcium Release ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Calcium Influx ◽  
Calcium Signalling ◽  
Chronic Fatigue ◽  
Diverse Range ◽  
Immune System Activation

AbstractCalcium is the most abundant mineral in the human body and is central to many physiological processes, including immune system activation and maintenance. Studies continue to reveal the intricacies of calcium signalling within the immune system. Perhaps the most well-understood mechanism of calcium influx into cells is store-operated calcium entry (SOCE), which occurs via calcium release-activated channels (CRACs). SOCE is central to the activation of immune system cells; however, more recent studies have demonstrated the crucial role of other calcium channels, including transient receptor potential (TRP) channels. In this review, we describe the expression and function of TRP channels within the immune system and outline associations with murine models of disease and human conditions. Therefore, highlighting the importance of TRP channels in disease and reviewing potential. The TRP channel family is significant, and its members have a continually growing number of cellular processes. Within the immune system, TRP channels are involved in a diverse range of functions including T and B cell receptor signalling and activation, antigen presentation by dendritic cells, neutrophil and macrophage bactericidal activity, and mast cell degranulation. Not surprisingly, these channels have been linked to many pathological conditions such as inflammatory bowel disease, chronic fatigue syndrome and myalgic encephalomyelitis, atherosclerosis, hypertension and atopy.

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