A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders

Journal of Neuroimmune Pharmacology, Journal Year: 2025, Volume and Issue: 20(1)

Published: Feb. 22, 2025

Most current information about neurological disorders and diseases is derived from direct patient animal studies. However, studies in many cases do not allow replication of the early stages disease and, therefore, offer limited opportunities to understand progression. On other hand, although use models allows us study mechanisms disease, they present significant limitations developing drugs for humans. Recently, 3D-cultured vitro human pluripotent stem cells have surfaced as a promising system. They potential connect findings with those models. In this comprehensive review, we discuss their application modeling neurodevelopmental conditions such Down Syndrome or Autism, neurodegenerative Alzheimer's Parkinson's, viral like Zika virus HIV. Furthermore, will different used prenatal exposure abuse, well challenges that must be met transform landscape research on brain disorders.

Language: Английский

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Serum interleukin-17 A and homocysteine levels in children with autism

BMC Neuroscience, Journal Year: 2024, Volume and Issue: 25(1)

Published: March 12, 2024

Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that typically emerges early in childhood. This study aimed to explore the potential link between serum levels of vitamin B12 and homocysteine (Hcy) severity ASD symptoms children. Methods In this study, 50 children diagnosed with comprised observation group, while healthy constituted control group. Serum IL-17 A, Hcy, folate, were compared group as well among different degrees severity. The correlation Childhood Rating Scale (CARS) score was examined. Additionally, relationship A Hcy their association explored. Results Compared demonstrated elevated alongside decreased folate levels. Individuals severe exhibited higher but lower those mild moderate ASD. CARS showed negative correlations positive patients. correlated Conclusion Children presented reduced increased potentially contributing onset

Language: Английский

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An In Vivo Model of Propionic Acid-Rich Diet-Induced Gliosis and Neuro-Inflammation in Mice (FVB/N-Tg(GFAPGFP)14Mes/J): A Potential Link to Autism Spectrum Disorder

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8093 - 8093

Published: July 25, 2024

Evidence shows that Autism Spectrum Disorder (ASD) stems from an interplay of genetic and environmental factors, which may include propionic acid (PPA), a microbial byproduct food preservative. We previously reported in vitro treatment neural stem cells with PPA leads to gliosis neuroinflammation. In this study, mice were exposed ad libitum PPA-rich diet for four weeks before mating. The same was maintained through pregnancy administered the offspring after weaning. brains studied at 1 5 months postpartum. Glial fibrillary acidic protein (astrocytic marker) significantly increased (1.53 ± 0.56-fold M 1.63 0.49-fold M) group brains. Tubulin IIIβ (neuronal decreased group. IL-6 TNF-α expression brain (IL-6: 2.48 1.25-fold M; TNF-α: 2.84 1.16-fold 2.64 1.42-fold, M), while IL-10 decreased. GPR41 p-Akt increased, PTEN (p-Akt inhibitor) data support role glia over-proliferation neuro-inflammation mediated by receptor PTEN/Akt pathway. These findings strongly our earlier study on ASD.

Language: Английский

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Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Inflammation, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 2, 2024

Abstract Autism spectrum disorder (ASD) is a neurodevelopmental characterized by impairments in social communication and behavior, frequently accompanied restricted repetitive patterns of interests or activities. The gut microbiota has been implicated the etiology ASD due to its impact on bidirectional pathway known as gut-brain axis. However, precise involvement causation unclear. This study critically examines recent evidence rationalize probable mechanism which symbiosis can induce neuroinflammation through intermediator cytokines metabolites. To develop ASD, loss integrity intestinal barrier, activation microglia, dysregulation neurotransmitters are caused neural inflammatory factors. It emphasized potential role neuroinflammatory intermediates linked alterations individuals with ASD. Specifically, like brain-derived neurotrophic factor, calprotectin, eotaxin, some metabolites microRNAs have considered etiological biomarkers. We also overviewed how probiotic trials may be used therapeutic strategy reestablish healthy balance microbiota. Evidence indicates induced dysregulated yet there little clarity based analysis circulating immune profile. deems repair load would lower chaos GI tract, correct mediators, modulate attenuate autism. interaction between brain, along biomarkers, serves foundational background for understanding etiology, diagnosis, prognosis, treatment autism disorder. Graphical

Language: Английский

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Roles of Prostaglandins and Cyclooxygenases in Autism Spectrum Disorder: A Comprehensive Review

Current Behavioral Neuroscience Reports, Journal Year: 2025, Volume and Issue: 12(1)

Published: Jan. 23, 2025

Abstract Purpose of Review Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with multifaceted etiologies. Emerging evidence implicates dysregulation prostaglandins and cyclooxygenase (COX) enzymes in ASD pathophysiology. This review aims to explore key mechanisms through which COX may influence ASD. Recent Findings research highlights significant roles for modulating Wnt (Wingless Int-1) signalling pathways, are known autism susceptibility as well regulating dendritic arborisation cerebellar function. Polymorphisms genes have also been linked ASD, indicating genetic component this dysregulation. Furthermore, show potential biomarkers Summary The accumulated underscores the involvement insight offers deeper understanding pave way more effective diagnostic treatment strategies.

Language: Английский

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Regional skull translocator protein elevation in autistic adults detected by PET-MRI

Brain Behavior and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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Novel Inflammatory Biomarkers for Autism Spectrum Disorder Detected by Plasma Olink Proteomics

Children, Journal Year: 2025, Volume and Issue: 12(2), P. 210 - 210

Published: Feb. 11, 2025

Background: Research evidence has recently shown an association between autism spectrum disorder (ASD) and inflammation. For example, the expression of inflammatory cytokines is abnormal in children with ASD, maternal inflammation can lead to ASD-like behavior offspring. These studies suggest that plays important role occurrence development ASD. Inflammatory may, therefore, be potential biomarkers for In present study, we sought systematically identify Methods: We used Olink proteomics comprehensively examine differentially expressed inflammation-related proteins 60 ASD 28 typical (TD). validated our findings using published data. Results: A total 18 were TD groups. Compared group, all was up-regulated group. Furthermore, eight showed good diagnostic efficacy, as delineated by area under curve (AUC) values > 0.7. To knowledge, this first time interleukin-17C (IL-17C), chemokine ligand (CCL)-19, CCL20 have been detected plasma (with AUC 0.839, 0.763, 0.756, respectively). also found there a negative correlation SRS scores. Conclusions: Multiple markers increased IL-17C, CCL19, exhibit biomarker candidates Elevated levels may enhance social ability

Language: Английский

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Chinese herbal medicine for the treatment of children with cerebral palsy: a meta-analysis of randomized controlled trials with core herbs exploration

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 26, 2025

Chinese herbal medicine (CHM) taken orally is frequently utilized to enhance functional ability and independence in cerebral palsy (CP); nonetheless, there a lack of current evidence regarding the efficacy oral CHM treating CP. Additionally, general complexities prescriptions often obscure underlying mechanisms. Our study aims assess CP, meta-analysis will be conducted on randomized clinical trials (RCTs). We searched Cochrane Library, PubMed, Embase, Scopus, PubMed Central, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), from 1990 2022. The primary outcome was improvement Effectiveness rate (ER). secondary motor function (GMFM). Subgroup analysis trial sequential (TSA) were confirm results consistency. Core CHMs investigated through system pharmacology analysis. Seventeen RCTs analyzed, which with Standard treatment (ST) compared ST alone. All participants aged <11 years. More group achieved prominent ER (RR: 1.21, 95% CI: 1.13-1.30, p-value < 0.001, I2 = 32%) higher GMFM (SMD: 1.49; 1.33-1.65, 92%). TSA also showed similar proper statistical power. CHMs, such as Glycyrrhiza uralensis Fisch. Ex DC., Poria cocos (Schw.) Wolf, Paeonia lactiflora Pall., processed Rehmannia glutinosa (Gaertn.) Astragalus mongholicus Bunge, Angelica sinensis (Oliv.) Diels, exerted effects immune modulation metabolism systems. subgroup using core or longer duration, studies enrolling CP spastic mixed type, mild-to-moderate severity had better outcomes groups less heterogeneity. may have positive impact managing pediatric CP; however, potential bias design should improved. Identifier CRD42023424754.

Language: Английский

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The Association Study Between Cytokines and the Risk for Cerebral Palsy

Mediators of Inflammation, Journal Year: 2025, Volume and Issue: 2025(1)

Published: Jan. 1, 2025

Background: Cerebral palsy (CP) is a debilitating condition characterized by abnormal movement or posture beginning early in development. Recent evidence has shown that immunological abnormalities are associated with an increased risk of CP. However, there no valuable biomarkers for CP diagnosis. Methods: In this case–control study, we recruited 108 children and 52 healthy as controls. The white blood cell (WBC) counts the levels inflammatory markers (interleukin‐1 β (IL‐1 ), sIL‐2R, interleukin‐6 (IL‐6), IL‐8, IL‐10, tumor necrosis factor‐ α (TNF‐ )), neuron‐specific enolase (NSE), immunoglobulin E (IgE), C3/C4 were measured results statistically analyzed. Subgroup analyzes based on age, complications, clinical subtypes also carried out. Results: Compared controls, patients had elevated NSE, TNF‐ . There differences WBC count, IL‐1 , IL‐6, IgE, C3, C4. analysis revealed significant personal–social developmental quotient (DQ) among different subtypes. We found gross motor DQ, adaptive DQ greater without epilepsy (EP) than those EP. Correlation positive correlations between fine DQ; moreover, sIL‐2R was positively correlated eosinophil (EO) count negatively age. NSE 1.64‐fold 1.66‐fold CP, respectively. peripheral exhibited good diagnostic value Moreover, receiver operating characteristic (ROC) curve increase area under (AUC) when these indicators combined. Conclusions: This study associations risk, suggesting might be useful identifying at high

Language: Английский

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CRISPRi-based screen of autism spectrum disorder risk genes in microglia uncovers roles of ADNP in microglia endocytosis and synaptic pruning

Molecular Psychiatry, Journal Year: 2025, Volume and Issue: unknown

Published: April 6, 2025

Abstract Autism Spectrum Disorders (ASD) are a set of neurodevelopmental disorders with complex biology. The identification ASD risk genes from exome-wide association studies and de novo variation analyses has enabled mechanistic investigations into how ASD-risk alter development. Most functional genomics have focused on the role these in neurons neural progenitor cells. However, roles for other cell types largely uncharacterized. There is evidence postmortem tissue that microglia, resident immune cells brain, appear activated ASD. Here, we used CRISPRi-based to systematically assess impact gene knockdown microglia activation phagocytosis. We developed an iPSC-derived microglia-neuron coculture system high-throughput flow cytometry readout synaptic pruning enable parallel screening phagocytosis beads, synaptosomes, pruning. Our screen identified ADNP , high-confidence genes, as modifier microglial found loss altered endocytic trafficking, remodeled proteomes, increased motility coculture.

Language: Английский

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