Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

MedComm, Год журнала: 2024, Номер 5(3)

Опубликована: Март 1, 2024

Abstract Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis reviewing ASD, this review systematically summarized current status progress pathogenesis, diagnostic markers, interventions ASD. We provided an overview molecular mechanisms identified by multi‐omics studies convergent mechanism in different genetic backgrounds. comorbidities, associated with important physiological metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, mitochondrial dysfunction), gut microbial were reviewed. non‐targeted omics targeting markers also Moreover, we methods behavioral educational interventions, intervention related to technological devices, on medical potential drug targets. This highlighted application high‐throughput emphasized importance seeking homogeneity from exploring convergence disease mechanisms, biomarkers, approaches, proposes that taking into account individuality commonality may be key achieve accurate diagnosis treatment

Язык: Английский

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Mouse strain-specific responses along the gut-brain axis upon fecal microbiota transplantation from children with autism

Gut Microbes, Год журнала: 2025, Номер 17(1)

Опубликована: Янв. 7, 2025

Several factors are linked to the pathophysiology of autism spectrum disorders (ASD); however, molecular mechanisms condition remain unknown. As intestinal problems and gut microbiota dysbiosis associated with ASD development severity, recent studies have focused on elucidating microbiota-gut-brain axis' involvement. This study aims explore through which might influence ASD. Briefly, we depleted conventional male BALB/cAnNCrl (Balb/c) C57BL/6J (BL/6) mice prior human fecal transplantation (hFMT) samples from children or their neurotypical siblings. We found mouse strain-specific responses hFMT. Notably, Balb/c exhibit decreased exploratory social behavior, show evidence intestinal, systemic, central inflammation accompanied metabolic shifts. BL/6 less changes after Our results reveal that alone induce in ASD-like highlight importance strain selection when investigating multifactorial conditions like

Язык: Английский

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Bridging animal models and humans: neuroimaging as intermediate phenotypes linking genetic or stress factors to anhedonia

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Янв. 23, 2025

Язык: Английский

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Autism spectrum disorder and a possible role of anti-inflammatory treatments: experience in the pediatric allergy/immunology clinic

Frontiers in Psychiatry, Год журнала: 2024, Номер 15

Опубликована: Июнь 24, 2024

Autism spectrum disorder (ASD 1 ) is a behaviorally defined syndrome encompassing markedly heterogeneous patient population. Many ASD subjects fail to respond the st line behavioral and pharmacological interventions, leaving parents seek out other treatment options. Evidence supports that neuroinflammation plays role in pathogenesis. However, underlying mechanisms likely vary for each patient, influenced by genetic, epigenetic, environmental factors. Although anti-inflammatory measures, mainly based on metabolic changes oxidative stress, have provided promising results some subjects, use of such measures requires careful selection clinical laboratory findings. Recent progress neuroscience molecular immunology has made it possible allow re-purposing currently available medications, used autoimmune chronic inflammatory conditions, as options subjects. On hand, emerging including biologic gate-keeper blockers, exert powerful effects specific mediators or signaling pathways. It will require both keen understanding action agents patients suitable treatment. This review attempt summarize already targeting patients, then applicable scientific rationale trial data, if available. In our experience, were treated under diagnoses autoimmune/autoinflammatory conditions and/or post-infectious neuroinflammation. there are little data specifically Therefore, these immunomodulating potential be discussed preclinical case reports, generated with medical conditions. hopefully highlight expanding scope treating

Язык: Английский

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Profiling metabolome of mouse embryonic cerebrospinal fluid following maternal immune activation

Journal of Biological Chemistry, Год журнала: 2024, Номер unknown, С. 107749 - 107749

Опубликована: Сен. 1, 2024

Язык: Английский

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Nurturing development: how a mother's nutrition shapes offspring's brain through the gut

Nutritional Neuroscience, Год журнала: 2024, Номер unknown, С. 1 - 23

Опубликована: Май 23, 2024

Pregnancy is a transformative period marked by profound physical and emotional changes, with far-reaching consequences for both mother child. Emerging research has illustrated the pivotal role of mother's diet during pregnancy in influencing prenatal gut microbiome subsequently shaping neurodevelopment her offspring. The intricate interplay between maternal health, nutrition, neurodevelopmental outcomes emerged as captivating field investigation within developmental science. Acting dynamic bridge fetus, microbiome, directly indirectly, impacts offspring's through diverse pathways. This comprehensive review delves into spectrum studies, clarifying putative mechanisms which modulating microbiota, orchestrates early stages brain development. Drawing insights from animal models human cohorts, this work underscores implications health trajectories offers glimpse formulation targeted interventions able to optimize prospect tailored dietary recommendations expectant mothers emerges promising accessible intervention foster growth beneficial bacteria, potentially leading enhanced cognitive reduced risks disorders.

Язык: Английский

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Kynurenic acid inflammatory signaling expands in primates and impairs prefrontal cortical cognition

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июнь 14, 2024

Summary Cognitive deficits from dorsolateral prefrontal cortex (dlPFC) dysfunction are common in neuroinflammatory disorders, including long-COVID, schizophrenia and Alzheimer’s disease, have been correlated with kynurenine inflammatory signaling. Kynurenine is further metabolized to kynurenic acid (KYNA) brain, where it blocks NMDA α7-nicotinic receptors (nic-α7Rs). These essential for neurotransmission dlPFC, suggesting that KYNA may cause higher cognitive these disorders. The current study found its synthetic enzyme, KAT II, greatly expanded expression primate dlPFC both glia neurons. Local application of onto neurons markedly reduced the delay-related firing needed working memory via actions at nic-α7Rs, while inhibition II enhanced neuronal aged macaques. Systemic administration agents reduce production similarly improved performance monkeys, a therapeutic avenue treatment

Язык: Английский

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1H-NMR-based metabolomics reveals metabolic alterations in early development of a mouse model of Angelman syndrome

Molecular Autism, Год журнала: 2024, Номер 15(1)

Опубликована: Июль 24, 2024

Abstract Background Angelman syndrome (AS) is a rare neurodevelopmental genetic disorder caused by the loss of function ubiquitin ligase E3A ( UBE3A ) gene, affecting approximately 1:15,000 live births. We have recently shown that mitochondrial in AS altered during mid to late embryonic brain development leading increased oxidative stress and enhanced apoptosis neural precursor cells. However, overall alterations metabolic processes are still unknown. Hence, as follow-up, we aim investigate profiles wild-type (WT) littermates identify which aberrant model mice development. Methods collected tissue samples from embryos at E16.5 performed metabolomic analyses using proton nuclear magnetic resonance 1 H-NMR) spectroscopy. Multivariate Univariate were determine significantly metabolites mice. Pathways associated with identified metabolite set enrichment analysis. Results Our analysis showed overall, fingerprint brains differed those their WT littermates. Moreover, revealed significant elevation distinct metabolites, such acetate, lactate, succinate compared samples. The elevated pyruvate metabolism glycolytic pathways. Limitations Only 14 successfully investigated present study. effect unidentified unresolved peaks was not determined. Additionally, conducted study on whole Employing high-resolution NMR studies different regions could further expand our knowledge regarding brain. Furthermore, increasing sample size reveal involvement more pathophysiology Conclusions Ube3a alters bioenergy-related these neurochemical changes be linked reactive oxygen species occurs

Язык: Английский

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The metabolic role of vitamin D in children’s neurodevelopment: a network study

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Июль 23, 2024

Neurodevelopmental disorders are rapidly increasing in prevalence and have been linked to various environmental risk factors. Mounting evidence suggests a potential role of vitamin D child neurodevelopment, though the causal mechanisms remain largely unknown. Here, we investigate how deficiency affects children's communication development, particularly relation Autism Spectrum Disorder (ASD). We do so by developing an integrative network approach that combines metabolomic profiles, clinical traits, neurodevelopmental data from pediatric cohort. Our results show low levels associated with changes metabolic networks tryptophan, linoleic, fatty acid metabolism. These correlate distinct ASD-related phenotypes, including delayed skills respiratory dysfunctions. Additionally, our analysis kynurenine serotonin sub-pathways may mediate effect on early life development. Altogether, findings provide metabolome-wide insights into as therapeutic option for ASD other disorders.

Язык: Английский

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Sex-Specific Behavioral and Molecular Responses to Maternal Lipopolysaccharide-Induced Immune Activation in a Murine Model: Implications for Neurodevelopmental Disorders

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(18), С. 9885 - 9885

Опубликована: Сен. 13, 2024

Maternal immune activation (MIA) during pregnancy has been increasingly recognized as a critical factor in the development of neurodevelopmental disorders, with potential sex-specific impacts that are not yet fully understood. In this study, we utilized murine model to explore behavioral and molecular consequences MIA induced by lipopolysaccharide (LPS) administration on embryonic day 12.5. Our findings indicate male offspring exposed LPS exhibited significant increases anxiety-like depression-like behaviors, while female did show comparable changes. Molecular analyses revealed alterations pro-inflammatory cytokine levels synaptic gene expression offspring, suggesting these disruptions may underlie observed differences. These results emphasize importance considering sex biological variable studies disorders highlight need for further investigations understand mechanisms driving outcomes. study contributes growing evidence prenatal challenges play pivotal role etiology underscores preventative approaches MIA.

Язык: Английский

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