The Autism Spectrum Disorder and Its Possible Origins in Pregnancy

International Journal of Environmental Research and Public Health, Journal Year: 2024, Volume and Issue: 21(3), P. 244 - 244

Published: Feb. 20, 2024

Autism Spectrum Disorder (ASD) belongs to the group of neurodevelopmental disorders, and has a high prevalence, affecting 1 in 100 children according data from World Health Organization (WHO). To be diagnosed with ASD, child must have persistent deficits communication social interactions, restricted repetitive patterns behavior, interests, or activities. Despite its etiology ASD is still uncertain, multifactorial characteristics, including those associated gestational period, where maternal exposure biological, chemical, physical hazards occurs, some which already been proposed as causes outcomes. Since pregnancy requires balance between maternal–fetal binomial, breakdown this caused by such environmental can lead altered fetal neurodevelopment, ASD. With firmly mind, review aims compile most recent on that may development help health professionals identify risk factors act for prevention management

Language: Английский

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Embryonic and larval exposure to propylparaben induces developmental and long-term neurotoxicity in zebrafish model

The Science of The Total Environment, Journal Year: 2023, Volume and Issue: 912, P. 168925 - 168925

Published: Nov. 29, 2023

Parabens are preservatives found in cosmetics, processed foods, and medications. The harmful repercussions on the central nervous system by one of most common parabens, propylparaben (PrP), yet unknown, especially during development. In this study, neurodevelopmental effects PrP long-term neurotoxicity were investigated zebrafish model, using an integrated approach. Zebrafish embryos exposed to two different concentrations (10 1000 μg/L), then larvae examined for their behavioral phenotypes (open-field behavior, startle response, circadian rhythmicity) relevant brain markers (cyp19a1b, pax6a, shank3a, gad1b). Long-term cognitive impacts sociability, cerebral functional asymmetry thigmotaxis also juveniles at 30 dpf 60 dpf. Moreover, proteomics gene expression analysis assessed brains zebrafish. Interestingly, was decreased high dose increased low juveniles. shank3a gad1b genes repressed both pointing possible neurodevelopment synaptogenesis. Proteomics evidenced alterations related development lipid metabolism. Overall, results demonstrated that early-life exposure promotes developmental persistent neurobehavioral affecting protein levels possibly associated with diseases.

Language: Английский

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Autism-related KLHL17 and SYNPO act in concert to control activity-dependent dendritic spine enlargement and the spine apparatus

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(8), P. e3002274 - e3002274

Published: Aug. 31, 2023

Dendritic spines, the tiny and actin-rich protrusions emerging from dendrites, are subcellular locations of excitatory synapses in mammalian brain that control synaptic activity plasticity. spines contain a specialized form endoplasmic reticulum (ER), i.e., spine apparatus, required for local calcium signaling is involved regulating dendritic enlargement Many autism-linked genes have been shown to play critical roles formation Among them, KLHL17 known during development. As brain-specific disease-associated gene, expected role brain, but it has not yet well characterized. In this study, we report expression mice strongly regulated by neuronal modulates distribution synaptopodin (SYNPO), marker apparatus. Both SYNPO F-actin-binding proteins linked autism. maintain structure apparatus mature contributes Our super-resolution imaging using expansion microscopy demonstrates indeed embedded into ER network closely adjacent ER/SYNPO complex. Using mouse genetic models, further show Klhl17 haploinsufficiency knockout result fewer containing clusters an alteration events at spines. Accordingly, activity-dependent activation (reflected extracellular signal-regulated kinase (ERK) phosphorylation C-FOS expression) impaired. addition, effect disrupting association similar results knockout, strengthening evidence act together regulate conclusion, our findings unravel controlling plasticity via its regulation clustering imply impaired etiology KLHL17-related disorders.

Language: Английский

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Implications of Kynurenine Pathway Metabolism for the Immune System, Hypothalamic–Pituitary–Adrenal Axis, and Neurotransmission in Alcohol Use Disorder

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4845 - 4845

Published: April 29, 2024

In recent years, there has been a marked increase in interest the role of kynurenine pathway (KP) mechanisms associated with addictive behavior. Numerous reports implicate KP metabolism influencing immune system, hypothalamic–pituitary–adrenal (HPA) axis, and neurotransmission, which underlie behavioral patterns characteristic addiction. An in-depth analysis results these new studies highlights interesting relationships, approaching alcohol use disorder (AUD) from broader neuroendocrine–immune system perspective may be crucial to better understanding this complex phenomenon. review, we provide an up-to-date summary information indicating relationship between AUD KP, both terms changes activity modulation as possible pharmacological approach for treatment AUD.

Language: Английский

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KLHL17 differentially controls the expression of AMPA‐ and KA‐type glutamate receptors to regulate dendritic spine enlargement

Journal of Neurochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: June 19, 2024

Abstract Kelch‐like family member 17 (KLHL17), an actin‐associated adaptor protein, is linked to neurological disorders, including infantile spasms and autism spectrum disorders. The key morphological feature of Klhl17 ‐deficient neurons impaired dendritic spine enlargement, resulting in the amplitude calcium events being increased. Our previous studies have indicated involvement F‐actin apparatus KLHL17‐mediated enlargement. Here, we show that KLHL17 further employs different mechanisms control expression two types glutamate receptors, is, α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionic acid receptor (AMPAR) kainate receptors (KARs), regulate enlargement influx. We deployed proteomics reveal interacts with N‐ethylmaleimide‐sensitive fusion protein (NSF) neurons, this interaction NSF enhancing levels. Consistent function regulating surface AMPAR, deficiency limits but not its total pathway also contributes synaptic distribution mediated by KLHL17. known act as mediating degradation KAR subunit GluK2 CUL3 ubiquitin ligase complex, impairs activity‐dependent GluK2. Herein, demonstrate critical increased influx neurons. Moreover, involved KLHL17‐regulated Thus, our study reveals controls AMPAR via at least mechanisms, consequently regulatory effects on these likely contribute neuronal features patients suffering from certain image

Language: Английский

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Genome-wide CNV analysis uncovers novel pathogenic regions in cohort of five multiplex families with neurodevelopmental disorders

Heliyon, Journal Year: 2023, Volume and Issue: 9(9), P. e19718 - e19718

Published: Sept. 1, 2023

Structural reorganization of chromosomes by genomic duplications and/or deletions are known as copy number variations (CNVs). Pathogenic and disease susceptible CNVs alter gene dosage its phenotypic expression that often leads to human genetic diseases including Neurological disorders. affecting same common genes in multiple neurodevelopmental disorders can better explain the shared clinical aetiology across brain diseases. Our study presents novel a cohort five multiplex consanguineous families with intellectual disability, microcephaly, ASD, epilepsy, neurological syndromic features. Cytoscan HD microarray suite has revealed genome wide deletions, LOH regions which co-segregating family members for rare phenotypes. This identifies 1q21.1 microduplication, 16p11.2 Xp11.22 4p12 microdeletion Xq21.1 significantly contribute primary onset progression first time Pakistani families. potential impact on understanding pathogenic predisposition appearance complex heterogeneous otherwise unexplained Identification altered is helpful improved diagnosis, management day-to-day life activities patients cognitive impairment counselling where consanguinity tradition. will expand knowledge genotype-phenotype future gateways therapeutics precision medicine research be open Pakistan.

Language: Английский

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Neuroimaging and epigenetic analysis reveal novel epigenetic loci in major depressive disorder

Psychological Medicine, Journal Year: 2024, Volume and Issue: 54(10), P. 2585 - 2598

Published: May 9, 2024

Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed identify novel MDD-associated epigenetic loci using methylation profiles and explore correlations between cortical thickness changes in patients with MDD.

Language: Английский

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A Genome-Wide Association Study of Dementia Using the Electronic Medical Record

BioMedInformatics, Journal Year: 2023, Volume and Issue: 3(1), P. 141 - 149

Published: Feb. 15, 2023

Dementia is characterized as a decline in cognitive function, including memory, language and problem-solving abilities. In this paper, we conducted Genome-Wide Association Study (GWAS) using data from the electronic Medical Records Genomics (eMERGE) network. This study has two aims, (1) to investigate genetic mechanism of dementia (2) discuss multiple p-value thresholds used address testing issues. Using genome-wide significant threshold (p≤5×10−8), identified four SNPs. Controlling False Positive Rate (FDR) level below 0.05 leads one extra SNP. Five SNPs that found are also supported by QQ-plot comparing observed p-values with expected p-values. All these five belong TOMM40 gene on chromosome 19. Other published studies independently validate relationship between dementia. Some use relaxed (p≤1×10−5) discover when statistical power insufficient. more powerful but cannot properly control false positives testing. We 13 threshold, which led discovery genes (such ATP10A-DT PTPRM). reported related brain development or neuro-development, indicating potential novel for Those loci may help identify targets developing new therapies. However, suggest them caution since they discovered without proper positive control.

Language: Английский

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The Emerging Roles ofLIS1 Biomechanics in Cellular and Cortical Homeostasis

Published: Aug. 8, 2023

Language: Английский

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Whole Genome Sequencing Revealed Inherited Rare Oligogenic Variants Contributing to Schizophrenia and Major Depressive Disorder in Two Families

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11777 - 11777

Published: July 21, 2023

Schizophrenia and affective disorder are two major complex mental disorders with high heritability. Evidence shows that rare variants significant clinical impacts contribute to the genetic liability of these disorders. Also, associated schizophrenia highly personalized; each patient may carry different variants. We used whole genome sequencing analysis study basis families depressive disorder. did not detect de novo, autosomal dominant, or recessive pathogenic likely psychiatric in families. Nevertheless, we identified multiple inherited unknown significance probands. In family 1, singleton schizophrenia, detected four genes implicated including p.Arg1627Trp LAMA2, p.Pro1338Ser CSMD1, p.Arg691Gly TLR4, Arg182X AGTR2. The TLR4 was from father, while other three were mother. 2, affected sisters diagnosed disorder, shared by disorders, p.Ala4551Gly FAT1, p.Val231Leu HOMER3, p.Ile185Met GPM6B. These assumed be their parents. Prompted findings, suggest interact lead conditions Our observations support conclusion heritability

Language: Английский

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