A Biopsychosocial Overview of Speech Disorders: Neuroanatomical, Genetic, and Environmental Insights

Biomedicines, Journal Year: 2025, Volume and Issue: 13(1), P. 239 - 239

Published: Jan. 20, 2025

Speech disorders encompass a complex interplay of neuroanatomical, genetic, and environmental factors affecting individuals’ communication ability. This review synthesizes current insights into the neuroanatomy, genetic underpinnings, influences contributing to speech disorders. Neuroanatomical structures, such as Broca’s area, Wernicke’s arcuate fasciculus, basal ganglia, along with their connectivity, play critical roles in production, comprehension, motor coordination. Advances understanding intricate brain networks involved language offer typical development pathophysiology Genetic studies have identified key genes neural migration synaptic further elucidating role mutations disorders, stuttering sound Beyond biological mechanisms, this explores profound impact psychological factors, including anxiety, depression, neurodevelopmental conditions, on individuals Psychosocial comorbidities often exacerbate complicating diagnosis treatment underscoring need for holistic approach managing these conditions. Future directions point toward leveraging testing, digital technologies, personalized therapies, alongside addressing psychosocial dimensions, improve outcomes comprehensive overview aims inform future research therapeutic advancements, particularly treating fluency like stuttering.

Language: Английский

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Neuromolecular Basis of Impaired Conditioned Taste Aversion Acquisition in Valproate-Induced Rat Model of Autism Spectrum Disorder

Genes, Journal Year: 2025, Volume and Issue: 16(2), P. 203 - 203

Published: Feb. 7, 2025

Autism spectrum disorder (ASD), defined by social, behavioral, and cognitive anomalies, is also associated with dysregulated appetite. ASD individuals, often described as "picky eaters", exhibit restricted dietary preferences a pronounced avoidance of novel foods. This suggests that the perceived safety specific tastants may be crucial determinant acceptance in ASD. Here, we explore hypothesis conditioned taste aversion (CTA), learned foods whose intake promotes sickness, exacerbated We assessed magnitude lithium chloride (LiCl)-induced CTA valproic acid (VPA) rat model autism versus healthy control rats. examined effect standard 3 mEq LiCl dose on transcript neuronal activation changes brain circuits mediating feeding behavior associative learning. Surprisingly, found while induced controls, even 6 was ineffective generating VPA at affected c-Fos immunoreactivity hypothalamus amygdala whereas rats it did not produce any changes. Gene expression analysis feeding-related genes (AgRP, NPY, OXT) those involved regulating stress anxiety (DOR MC3R) were differentially regulated Interestingly, transcripts for COMT1, AgRP, OXT, MC3R downregulated saline-treated compared to controls. conclude show blunted responsiveness, which reflected differential impact promote acquisition autistic individuals.

Language: Английский

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Non-Invasive Assessment of Neurogenesis Dysfunction in Fetuses with Early-Onset Growth Restriction Using Fetal Neuronal Exosomes Isolating from Maternal Blood: A Pilot Study

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1497 - 1497

Published: Feb. 11, 2025

The vector of modern obstetrics is aimed at finding ways to predict various placenta-associated complications, including those associated with neuronal dysfunction on in fetal growth restriction (FGR). technology exosome (FNE) isolation from the maternal bloodstream opens up unique opportunities for detecting early signs brain damage. Using this method, FNEs were isolated blood pregnant women and without early-onset FGR, expression a number proteins their composition was assessed (Western blotting). Significant changes level involved neurogenesis (pro-BDNF (brain-derived neurotrophic factor), pro-NGF (nerve TAG1/Contactin2) presynaptic transmission (Synapsin 1, Synaptophysin) revealed. preliminary data FNE that perform post-translational modifications—sumoylation (SUMO UBC9) neddylation (NEDD8, UBC12)—were obtained. A relationship established between altered protein neonatal outcomes newborns restriction. Our study new possibilities non-invasive prenatal monitoring neurodevelopment disorders correction diseases.

Language: Английский

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Neurobiological Relationships Between Neurodevelopmental Disorders and Mood Disorders

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 307 - 307

Published: March 14, 2025

According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), neurodevelopmental disorders (NDDs) are a group conditions that arise early in development characterized by deficits personal, social, academic, or occupational functioning. These frequently co-occur include such as autism spectrum disorder (ASD) attention-deficit/hyperactivity (ADHD). Mood (MDs), major depressive bipolar disorder, also pose significant global health challenges due their high prevalence substantial impact on quality life. Emerging evidence highlights overlapping neurobiological mechanisms between NDDs MDs, including shared genetic susceptibilities, neurotransmitter dysregulation (e.g., dopaminergic serotonergic pathways), neuroinflammation, hypothalamic–pituitary–adrenal (HPA) axis dysfunction. Environmental factors early-life adversity further exacerbate these vulnerabilities, contributing complexity clinical presentation comorbidity. Functional neuroimaging studies reveal altered connectivity brain regions critical for emotional regulation executive function, prefrontal cortex amygdala, across disorders. Despite advances, integrative diagnostic frameworks targeted therapeutic strategies remain underexplored, limiting effective intervention. This review synthesizes current knowledge underpinnings emphasizing need multidisciplinary research, genetic, pharmacological, psychological approaches, unified diagnosis treatment. Addressing intersections can improve outcomes enhance life individuals affected

Language: Английский

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The E3 Ubiquitin Ligase PRAJA1: A Key Regulator of Synaptic Dynamics and Memory Processes with Implications for Alzheimer’s Disease

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2909 - 2909

Published: March 23, 2025

The precise regulation of synaptic function by targeted protein degradation is fundamental to learning and memory, yet the roles many brain-enriched E3 ubiquitin ligases in this process remain elusive. Here, we uncover a critical previously unappreciated role for ligase PRAJA1 orchestrating plasticity hippocampus-dependent memory. Utilizing C57BL/6 5xFAD male mice employing multi-faceted approach including biochemistry, molecular biology, vitro electrophysiology, behavioral assays, demonstrate that long-term potentiation (LTP) induction triggers rapid, proteasome-dependent downregulation within CA1 region hippocampus. Critically, selective knockdown vivo profoundly enhanced both object recognition spatial while disrupting normal exploratory behavior. Mechanistically, reveal acts as key regulator architecture transmission: its leads reduction proteins spine density, influencing excitatory/inhibitory balance facilitating plasticity. Conversely, increased expression potentiates GABAergic transmission. Furthermore, identify spinophilin novel substrate PRAJA1, suggesting direct link between remodeling. Strikingly, our findings implicate dysregulation pathogenesis Alzheimer's disease, positioning potential therapeutic target cognitive enhancement neurodegenerative conditions. These results unveil brake on memory formation, offering promising new avenue understanding potentially treating impairment.

Language: Английский

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Cullin-RING Ubiquitin Ligases in Neurodevelopment and Neurodevelopmental Disorders

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 810 - 810

Published: March 28, 2025

Ubiquitination is a dynamic and tightly regulated post-translational modification essential for modulating protein stability, trafficking, function to preserve cellular homeostasis. This process orchestrated through hierarchical enzymatic cascade involving three key enzymes: the E1 ubiquitin-activating enzyme, E2 ubiquitin-conjugating E3 ubiquitin ligase. The final step of ubiquitination catalyzed by ligase, which facilitates transfer from enzyme substrate, thereby dictating proteins undergo ubiquitination. Emerging evidence underscores critical roles ligases in neurodevelopment, regulating fundamental processes such as neuronal polarization, axonal outgrowth, synaptogenesis, synaptic function. Mutations genes encoding consequent dysregulation these pathways have been increasingly implicated spectrum neurodevelopmental disorders, including autism disorder, intellectual disability, attention-deficit/hyperactivity disorder. review synthesizes current knowledge on molecular mechanisms underlying neurodevelopment Cullin-RING ligases—the largest subclass ligases—and their involvement pathophysiology disorders. A deeper understanding holds significant promise informing novel therapeutic strategies, ultimately advancing clinical outcomes individuals affected

Language: Английский

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Identification of E3 Ubiquitin Ligase Substrates Using Biotin Ligase-Based Proximity Labeling Approaches

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 854 - 854

Published: April 2, 2025

Ubiquitylation is a post-translational modification originally identified as the first step in protein degradation by ubiquitin–proteasome system. also known to regulate many cellular processes without degrading ubiquitylated proteins. Substrate proteins are specifically recognized and ubiquitin ligases. It necessary identify substrates for each ligase understand physiological pathological roles of ubiquitylation. Recently, promiscuous mutant biotin derived from Escherichia coli, BioID, its variants have been utilized analyze protein–protein interaction. In this review, we summarize current knowledge regarding molecular mechanisms underlying ubiquitylation, BioID-based approaches interactome studies, application BirA identification substrates.

Language: Английский

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Genome Sequencing Identifies 13 Novel Candidate Risk Genes for Autism Spectrum Disorder in a Qatari Cohort

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(21), P. 11551 - 11551

Published: Oct. 27, 2024

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social communication, restricted interests, and repetitive behaviors. Despite considerable research efforts, the genetic complexity of ASD remains poorly understood, complicating diagnosis treatment, especially Arab population, with its diversity linked to migration, tribal structures, high consanguinity. To address scarcity data Middle East, we conducted genome sequencing (GS) on 50 subjects their unaffected parents. Our analysis revealed 37 single-nucleotide variants from 36 candidate genes over 200 CGG repeats FMR1 gene one subject. The identified were classified as uncertain, likely pathogenic, or pathogenic based in-silico algorithms ACMG criteria. Notably, 52% homozygous, indicating recessive architecture this population. This finding underscores significant impact consanguinity within Qatari which could be utilized counseling/screening program Qatar. We also discovered single nucleotide 13 novel not previously associated ASD: ARSF, BAHD1, CHST7, CUL2, FRMPD3, KCNC4, LFNG, RGS4, RNF133, SCRN2, SLC12A8, USP24, ZNF746. investigation categorized into seven groups, highlighting roles cognitive development, including ubiquitin pathway, transcription factors, solute carriers, kinases, glutamate receptors, chromatin remodelers, ion channels.

Language: Английский

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Whole Exome Sequencing and Panel-Based Analysis in 176 Spanish Children with Neurodevelopmental Disorders: Focus on Autism Spectrum Disorder and/or Intellectual Disability/Global Developmental Delay

Genes, Journal Year: 2024, Volume and Issue: 15(10), P. 1310 - 1310

Published: Oct. 11, 2024

Background: Neurodevelopmental disorders (NDDs) represent a significant challenge in pediatric genetics, often requiring advanced diagnostic tools for the accurate identification of genetic variants. Objectives: To determine yield whole exome sequencing (WES) with targeted gene panels children neurodevelopmental (NDDs). Methods: This observational, prospective study included total 176 Spanish-speaking patients (NDDs), encompassing intellectual disability (ID), global developmental delay (GDD), and/or autism spectrum disorder (ASD). Participants were recruited from January 2019 to 2023 at University Hospital Madrid, Spain. Clinical and sociodemographic variables recorded, along results. The age range subjects was 9 months 16 years, percentage males 72.1%. calculated both before after parental testing via Sanger DNA sequencing. Results: children: 67 (38.1%) ID, 62 (35.2%) ASD, 47 (26.7%) ASD + ID. proband-only 12.5% (22/176). By group, 3.2% 12.7% 20.8% ID group. Variants uncertain significance (VUS) found 39.8% (70/176). After testing, some variants reclassified as “likely pathogenic”, increasing by 4.6%, an overall 17.1%. Diagnostic higher syndromic (70.6%% vs. 29.4%; p = 0.036). Conclusions: A sequential approach utilizing WES followed panel-based analysis, starting index case and, when appropriate, including parents, proves be cost-effective strategy. is particularly suitable complex conditions, it allows potentially causative genes beyond those covered panels, providing more comprehensive analysis. Including enhances improves accuracy, especially cases (VUS), thereby advancing our understanding NDDs.

Language: Английский

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Dynamic Expression of Genes Encoding Ubiquitin Conjugating Enzymes (E2s) During Neuronal Differentiation and Maturation: Implications for Neurodevelopmental Disorders and Neurodegenerative Diseases

Genes, Journal Year: 2024, Volume and Issue: 15(11), P. 1381 - 1381

Published: Oct. 26, 2024

Background: The ubiquitination process plays a crucial role in neuronal differentiation and function. Numerous studies have focused on the expression functions of E3 ligases during these different stages, far fewer E2 conjugating enzymes. In mice, as humans, E2s belong to 17 enzyme families. Objectives: We analyzed by real-time PCR dynamics all known genes an vitro mouse hippocampal cultures, after, we their stimulation with N-methyl-D-aspartate (NMDA). Results: found that 36 38 were expressed neurons. Many up-regulated neuritogenesis and/or synaptogenesis such Ube2h, Ube2b, Aktip. Rapid delayed responses NMDA associated increased several genes, Ube2i, SUMO-conjugating enzyme. also observed similar profiles within same gene family, consistent presence transcription factor binding sites respective promoter sequences. Conclusions: Our study indicates specific are correlated changes activity. A better understanding regulation function is needed understand played physiological mechanisms pathophysiological alterations involved neurodevelopmental or neurodegenerative diseases.

Language: Английский

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