scholarly journals Associations between Monocyte Cytokine Profiles and Co-Morbid Conditions in Autism Spectrum Disorders

2021 ◽  
Author(s):  
Harumi Jyonouchi ◽  
Lee Geng
Keyword(s):  
Treatment Options ◽  
Autism Spectrum ◽  
Acute Onset ◽  
Behavioral Symptoms ◽  
Cytokine Profiles ◽  
Tnf Α ◽  
Gi Symptoms ◽  
Soluble Tnf Receptor ◽  
Factor Α ◽  
Morbid Conditions

Autism spectrum disorder (ASD) is a behaviorally defined syndrome with frequent co-morbidities. Evidence indicate a role of innate immunity in ASD pathogenesis. This study addressed whether innate immune abnormalities are associated with ASD co-morbid conditions and/or other clinical co-variables when assessed as changes in monocyte cytokine profiles. This study included 109 ASD (median 11.5 year) and 26 non-ASD subjects (median 11.4 year). Monocyte cytokine profiles were evaluated in association with age/ethnicity, ASD severity, medications, and co-morbidities present in >15% of ASD subjects [gastrointestinal (GI) symptoms, epilepsy, allergic rhinitis, specific antibody deficiency (SAD), and fluctuating behavioral symptoms resembling pediatric acute-onset neuropsychiatric syndrome (PANS)]. ASD severity did not affect frequency of co-morbid conditions. GI symptoms, epilepsy, SAD, and PANS like symptoms revealed associations with changes in production of tumor necrosis factor-α (TNF-α)/soluble TNF-receptor II (sTNFRII), interleukin-1ß (IL-1ß)/IL-6/IL-10, and IL-6, respectively, mostly independent of other co-variables. ASD severity was associated with changes in multiple cytokines but frequently affected by other clinical co-variables. Our findings revealed associations between specific monocyte cytokine profiles and certain co-morbid conditions in ASD subjects, independent of other clinical co-variables. Our findings will aid in assessing treatment options for ASD co-morbidities and their effects on ASD behavioral symptoms.

scholarly journals TNF-α expression ratio of M1/M2 macrophages is a potential adjunctive tool for the diagnosis of autism spectrum disorder

2020 ◽  
Author(s):  
Takahira Yamauchi ◽  
Manabu Makinodan ◽  
Michihiro Toritsuka ◽  
Kazuki Okumura ◽  
Yoshinori Kayashima ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Area Under The Curve ◽  
Positive Likelihood Ratio ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
M2 Macrophages ◽  
Expression Ratio ◽  
Tnf Α ◽  
Significant Difference ◽  
Factor Α

Abstract Background The etiology of autism spectrum disorder (ASD) is complex. Its pathobiology is characterized by enhanced inflammatory activities; however, the exact ASD pathobiology remains unclear. Some cases of ASD are difficult to diagnose using existing psychological assessments because the careful exclusion of other psychiatric disorders is challenging. To distinguish between the appropriate targets for interventions and research, the demand for identifying efficient diagnostic biomarkers is increasing. This study aimed to find an inflammatory indicator beneficial for the diagnosis of ASD.Methods Cytokine mRNA expression, including tumor necrosis factor-α (TNF-α), was measured in the differentiated M1 and M2 macrophages of ASD patients (n = 29) and typically developed (TD) individuals (n = 30). TNF-α expression was also measured in the monocytes of ASD patients (n = 7) and TD individuals (n = 6).Results TNF-α expression in M1 macrophages and TNF-α expression ratio of M1/M2 macrophages were markedly higher in ASD patients than in TD subjects; however, this difference was not observed in M2 macrophages (M1: p < 0.01; ratio of M1/M2: p < 0.0001; M2: p > 0.05), suggesting that this indicator could be a useful tool for diagnosing ASD (M1: sensitivity = 34.5%, specificity = 96.7%, area under the curve (AUC) = 0.74, positive likelihood ratio (PLR) = 10.34; ratio of M1/M2: sensitivity = 55.2%, specificity = 96.7%, AUC = 0.79, PLR = 16.55). However, there was no significant difference in the TNF-α expression in monocytes between ASD and TD individuals (p > 0.05).Conclusion These findings suggest that TNF-α expression in differentiated macrophages represents a novel adjunctive tool for the diagnosis of ASD.

scholarly journals The Gut-Brain-Microbiome Axis and Its Link to Autism: Emerging Insights and the Potential of Zebrafish Models

2021 ◽  
Vol 9 ◽  
Author(s):  
David M. James ◽  
Elizabeth A. Davidson ◽  
Julio Yanes ◽  
Baharak Moshiree ◽  
Julia E. Dallman
Keyword(s):  
Quality Of Life ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Behavioral Symptoms ◽  
Great Promise ◽  
Contributory Factor ◽  
Holistic View ◽  
Gi Symptoms ◽  
Negative Impacts

Research involving autism spectrum disorder (ASD) most frequently focuses on its key diagnostic criteria: restricted interests and repetitive behaviors, altered sensory perception, and communication impairments. These core criteria, however, are often accompanied by numerous comorbidities, many of which result in severe negative impacts on quality of life, including seizures, epilepsy, sleep disturbance, hypotonia, and GI distress. While ASD is a clinically heterogeneous disorder, gastrointestinal (GI) distress is among the most prevalent co-occurring symptom complex, manifesting in upward of 70% of all individuals with ASD. Consistent with this high prevalence, over a dozen family foundations that represent genetically distinct, molecularly defined forms of ASD have identified GI symptoms as an understudied area with significant negative impacts on quality of life for both individuals and their caregivers. Moreover, GI symptoms are also correlated with more pronounced irritability, social withdrawal, stereotypy, hyperactivity, and sleep disturbances, suggesting that they may exacerbate the defining behavioral symptoms of ASD. Despite these facts (and to the detriment of the community), GI distress remains largely unaddressed by ASD research and is frequently regarded as a symptomatic outcome rather than a potential contributory factor to the behavioral symptoms. Allowing for examination of both ASD’s impact on the central nervous system (CNS) as well as its impact on the GI tract and the associated microbiome, the zebrafish has recently emerged as a powerful tool to study ASD. This is in no small part due to the advantages zebrafish present as a model system: their precocious development, their small transparent larval form, and their parallels with humans in genetics and physiology. While ASD research centered on the CNS has leveraged these advantages, there has been a critical lack of GI-centric ASD research in zebrafish models, making a holistic view of the gut-brain-microbiome axis incomplete. Similarly, high-throughput ASD drug screens have recently been developed but primarily focus on CNS and behavioral impacts while potential GI impacts have not been investigated. In this review, we aim to explore the great promise of the zebrafish model for elucidating the roles of the gut-brain-microbiome axis in ASD.

Hypericin ameliorates maternal separation-induced cognitive deficits and hippocampal inflammation in rats

2020 ◽  
Vol 20 ◽  
Author(s):  
Sedigheh Khanjani Jolodar ◽  
Mohammadreza Bigdeli ◽  
Akbar Hajizadeh Moghaddam
Keyword(s):  
Cognitive Deficits ◽  
Maternal Separation ◽  
Autism Spectrum ◽  
Dopamine Level ◽  
Tnf Α ◽  
Severe Change ◽  
Factor Α ◽  
Inflammation Factor ◽  
The Brain ◽  
Necrosis Factor

Objective: Maternal separation as an epigenetic agent provokes a severe change in the brain such as inflammation response, which is a key risk factor for the progression of autism spectrum disorders (ASD). Methods: This study evaluated the preventive effect of hypericin on maternal separation-induced cognitive deficits and hippocampal inflammation. Here, we reported that pups are subjected to maternal separations for 1 h per day from postnatal days (PND) 1–9 displayed apparent memory impairment in young rats (postnatal day 34) compared to controls group. Furthermore, the maternal separation significantly increased inflammation factors in hippocampus area. Anti-inflammation constituent shed light on treating ASD. Results: In this study, we found that, treatment with hypericin (10 and 50 mg/kg) significantly suppresses expression of hippocampal interleukin-6 (IL-6) and tumor necrosis factor α (TNF- α) in maternal separation rat model. Also, we found that hypericin prevented the decrease of hippocampal dopamine level in offspring of maternal separation rats. Conclusion: The data indicated that hypericin may play a neuroprotective role in hippocampal cell and ameliorates dysfunctions in memory and level of inflammation factor in this autism model. Thus, hypericin could be used as an intervention for treating ASD.

scholarly journals UP1306: A Composition Containing Standardized Extracts of Acacia catechu and Morus alba for Arthritis Management

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 272 ◽  
Author(s):  
Mesfin Yimam ◽  
Teresa Horm ◽  
Laura Wright ◽  
Ping Jiao ◽  
Mei Hong ◽  
...  
Keyword(s):  
Treatment Options ◽  
Cartilage Degradation ◽  
Morus Alba ◽  
Root Bark ◽  
Botanical Composition ◽  
Collagen Induced Arthritis ◽  
Arthritis Severity ◽  
Tnf Α ◽  
Acacia Catechu ◽  
Factor Α

Osteoarthritis (OA) is characterized by progressive articular cartilage degradation. Although there have been significant advances in OA management, to date, there are no effective treatment options to modify progression of the disease. We believe these unmet needs could be bridged by nutrients from natural products. Collagen induced arthritis in rats was developed and utilized to evaluate anti-inflammatory and cartilage protection activity of orally administered botanical composition, UP1306 (50 mg/kg) and Methotrexate (75 µg/kg) daily for three weeks. Objective arthritis severity markers, urine, synovial lavage, and serum were collected. At necropsy, the hock joint from each rat was collected for histopathology analysis. Urinary cartilage degradation marker (CTX-II), pro-inflammatory cytokines (tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and IL-6), and proteases (Matrix Metallopeptidase 3 (MMP3) and 13) were measured. Rats treated with UP1306 showed statistically significant improvements in arthritis severity markers, including uCTX-II (91.4% vs. collagen-induced arthritis (CIA)), serum IL-1β, TNF-α, and IL-6 levels as well as synovial MMP-13. The histopathology data were also well aligned with the severity score of arthritis for both UP1306 and Methotrexate. UP1306, a botanical composition that contains a standardized blend of extracts from the heartwood of Acacia catechu and the root bark of Morus alba, could potentially be considered as a dietary supplement product for the management of arthritis.

scholarly journals A Systematic Review of the Role of Prebiotics and Probiotics in Autism Spectrum Disorders

Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 129 ◽  
Author(s):  
Qin Ng ◽  
Wayren Loke ◽  
Nandini Venkatanarayanan ◽  
Donovan Lim ◽  
Alex Soh ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Autism Spectrum ◽  
Behavioral Symptoms ◽  
Open Label ◽  
Double Blind ◽  
Children With Asd ◽  
Gi Symptoms ◽  
Significant Difference ◽  
Different Strains

Background: Autism spectrum disorder (ASD) is a complex developmental condition typically characterized by deficits in social and communicative behaviors as well as repetitive patterns of behaviors. Despite its prevalence (affecting 0.1% to 1.8% of the global population), the pathogenesis of ASD remains incompletely understood. Patients with ASD are reported to have more frequent gastrointestinal (GI) complaints. There is some anecdotal evidence that probiotics are able to alleviate GI symptoms as well as improve behavioral issues in children with ASD. However, systematic reviews of the effect of prebiotics/probiotics on ASD and its associated symptoms are lacking. Methods: Using the keywords (prebiotics OR probiotics OR microbiota OR gut) AND (autism OR social OR ASD), a systematic literature search was conducted on PubMed, EMBASE, Medline, Clinicaltrials.gov and Google Scholar databases. The inclusion criteria were original clinical trials, published in English between the period 1st January 1988 and 1st February 2019. Results: A total of eight clinical trials were systematically reviewed. Two clinical trials examined the use of prebiotic and/or diet exclusion while six involved the use of probiotic supplementation in children with ASD. Most of these were prospective, open-label studies. Prebiotics only improved certain GI symptoms; however, when combined with an exclusion diet (gluten and casein free) showed a significant reduction in anti-sociability scores. As for probiotics, there is limited evidence to support the role of probiotics in alleviating the GI or behavioral symptoms in children with ASD. The two available double-blind, randomized, placebo-controlled trials found no significant difference in GI symptoms and behavior. Conclusion: Despite promising preclinical findings, prebiotics and probiotics have demonstrated an overall limited efficacy in the management of GI or behavioral symptoms in children with ASD. In addition, there was no standardized probiotics regimen, with multiple different strains and concentrations of probiotics, and variable duration of treatments.

scholarly journals Inflammatory Biomarkers are Correlated with Some Forms of Regressive Autism Spectrum Disorder

2019 ◽  
Vol 9 (12) ◽  
pp. 366 ◽  
Author(s):  
Margherita Prosperi ◽  
Letizia Guiducci ◽  
Diego G. Peroni ◽  
Chiara Narducci ◽  
Melania Gaggini ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Developmental Delay ◽  
Plasminogen Activator Inhibitor ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Inflammatory Biomarkers ◽  
Plasminogen Activator Inhibitor 1 ◽  
Tnf Α ◽  
Gi Symptoms ◽  
Pai 1

Background: Several studies have tried to investigate the role of inflammatory biomarkers in Autism Spectrum Disorder (ASD), and their correlations with clinical phenotypes. Despite the growing research in this topic, existing data are mostly contradictory. Methods: Eighty-five ASD preschoolers were assessed for developmental level, adaptive functioning, gastrointestinal (GI), socio-communicative and psychopathological symptoms. Plasma levels of leptin, resistin, plasminogen activator inhibitor-1 (PAI-1), macrophage chemoattractant protein-1 (CCL2), tumor necrosis factor-alfa (TNF-α), and interleukin-6 (IL-6) were correlated with clinical scores and were compared among different ASD subgroups according to the presence or absence of: (i) GI symptoms, (ii) regressive onset of autism. Results: Proinflammatory cytokines (TNF-α, IL-6 and CCL2) were lower than those reported in previous studies in children with systemic inflammatory conditions. GI symptoms were not correlated with levels of inflammatory biomarkers except for resistin that was lower in ASD-GI children (p = 0.032). Resistin and PAI-1 levels were significantly higher in the group with “regression plus a developmental delay” onset (Reg+DD group) compared to groups without regression or with regression without a developmental delay (p < 0.01 for all). Conclusions: Our results did not highlight the presence of any systemic inflammatory state in ASD subjects neither disentangling children with/without GI symptoms. The Reg + DD group significantly differed from others in some plasmatic values, but these differences failed to discriminate the subgroups as possible distinct ASD endo-phenotypes.

scholarly journals Microglia-triggered hyperexcitability in the cerebellum depresses animal behaviors

2018 ◽  
Author(s):  
Masamichi Yamamoto ◽  
Minsoo Kim ◽  
Hirohiko Imai ◽  
Gen Ohtsuki
Keyword(s):  
Depressive Disorders ◽  
Autism Spectrum ◽  
Two Photon ◽  
Atp Secretion ◽  
Endotoxin Exposure ◽  
Tnf Α ◽  
Cytokine Tumor Necrosis Factor ◽  
Behavioral Impairments ◽  
Factor Α

AbstractClinical studies have suggested that cerebellar dysfunction is involved in various psychiatric disorders, including autism spectrum disorders, dyslexia, and depressive disorders. However, the physiological aspect is less-advanced. Here, we comprehensively investigated the immune-triggered excitability plasticity in the cerebellum. Activated microglia (MG) via exposure to bacterial endotoxin lipopolysaccharide or heat-killed Gram-negative bacteria induced a potentiation of the excitability of Purkinje neurons, which was suppressed by MG-activity inhibitor and MG-depletion. An inflammatory cytokine, tumor necrosis factor-α (TNF-α) released from MG triggered this plasticity. While our new two-photon FRET ATP-imaging showed an increase in ATP concentration following endotoxin exposure, both TNF-α and ATP secretion facilitated synaptic transmission. Inflammation in the cerebellar anterior vermis in vivo immobilized animals, and reduced sociability. Such abulia-like behavioral impairments were reverted by TNF-α-inhibition and MG-depletion. Resting-state functional MRI revealed overconnectivity between the inflamed cerebellum and prefrontal neocortical regions, which may underlie the psychomotor depressiveness in animals.

scholarly journals Abdominal Pain in Children and Adolescents with Autism Spectrum Disorder: a Systematic Review

2021 ◽  
Author(s):  
Julia Lanyi ◽  
Christopher Flynn ◽  
Arlene Mannion ◽  
Leanne Maher ◽  
Katie Naughton ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Abdominal Pain ◽  
Children And Adolescents ◽  
Treatment Options ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Future Research ◽  
Inclusion Criteria ◽  
Gi Symptoms ◽  
Adolescents With Autism

AbstractThe aim of this study was to review the existing literature on abdominal pain in children and adolescents with autism spectrum disorder. Systematic search of four databases (PsycINFO, ERIC, PubMed, MEDLINE) identified 13 studies that met the inclusion criteria. Articles were analyzed for common themes, including the prevalence of abdominal pain and gastrointestinal (GI) symptoms, associations between abdominal pain/GI symptoms and behavioral and emotional concerns, associations between abdominal pain/GI symptoms, and other comorbid disorders and treatment options based on gut bacteria, diet, and probiotics. Reasons for varying prevalence rates, persistence of symptoms over time, comorbidities, and different treatment options are discussed. Clinical implications and recommendations for future research are also discussed.

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