Shank3 deficiency alters midbrain GABAergic neuron morphology, GABAergic markers and synaptic activity in primary striatal neurons DOI Creative Commons
Zuzana Bačová, Bohumila Jurkovičová-Tarabová, T. Havránek

и другие.

Molecular Brain, Год журнала: 2024, Номер 17(1)

Опубликована: Сен. 27, 2024

Abstract Abnormalities in gamma-aminobutyric acid (GABA)ergic neurotransmission play a role the pathogenesis of autism, although mechanisms responsible for alterations specific brain regions remain unclear. Deficits social motivation and interactions are core symptoms likely due to defects dopaminergic neural pathways. Therefore, investigating morphology functional roles GABAergic neurons within projection areas could elucidate underlying etiology autism. The aim this study was (1) compare arborization glutamate decarboxylase (GAD)-positive from midbrain tegmentum; (2) evaluate synaptic activity primary striatum; (3) assess postsynaptic puncta ventral striatum wild-type (WT) Shank3 -deficient mice. We found significant decrease number short neurites GAD positive tegmentum application blocker GABA A receptors (GABA R) revealed significantly increased frequency spontaneous currents (sPSCs) striatal compared their WT counterparts. mean absolute amplitude events higher also observed reduction gephyrin/GABA R γ2 colocalization adult male gene expression collybistin lower nucleus accumbens while gephyrin were tegmental area (VTA) Shank3- deficient In conclusion, deficiency leads impaired function areas. These changes may underlie autistic symptoms, potential interventions modulating pathways represent new treatment modality.

Язык: Английский

Dopamine Dysregulation in Reward and Autism Spectrum Disorder DOI Creative Commons
Kenneth Blum, Abdalla Bowirrat,

Keerthy Sunder

и другие.

Brain Sciences, Год журнала: 2024, Номер 14(7), С. 733 - 733

Опубликована: Июль 22, 2024

Autism spectrum disorder (ASD) is primarily characterized by core deficits in social skills, communication, and cognition repetitive stereotyped behaviors. These manifestations are variable between individuals, ASD pathogenesis complex, with over a thousand implicated genes, many epigenetic factors, multiple environmental influences. The mesolimbic dopamine (DA) mediated brain reward system held to play key role, but the rapidly expanding literature reveals intricate, nuanced signaling involving wide array of loci, neurotransmitters receptor subtypes, neuronal variants. How altered DA may constitute downstream convergence manifold causal origins not well understood. A clear working framework help delineate common stages potential diagnostic interventional opportunities. Hence, we summarize known natural history context emerging data perspectives update signaling. Then, against this backdrop, proffer provisional that organizes into successive levels, including (1) genetic changes, (2) disrupted pathways, (3) dysregulated neurotransmitter/DA signaling, finally, (4) neurocognitive behavior possible antagonist/agonist based interventions. This subdivision logical progression potentially addressable parts facilitate rational formulation diagnostics targeted treatments.

Язык: Английский

Процитировано

4

Optimal dose of oxytocin to improve social impairments and repetitive behaviors in autism spectrum disorders: meta-analysis and dose–response meta-analysis of randomized controlled trials DOI Creative Commons
Yingying Zhang, Xiaolu Zhang,

Linghong Huang

и другие.

Frontiers in Psychiatry, Год журнала: 2025, Номер 15

Опубликована: Янв. 29, 2025

Introduction Social impairments and repetitive behaviors are at the core symptoms of autism spectrum disorder (ASD). Intranasal administration neuropeptide oxytocin (OXT) is a promising treatment. However, there have been inconsistencies in effects OXT on social behaviors. Methods A comprehensive search PubMed, Cochrane Library, Embase, Web Science was conducted to gather randomized controlled trials (RCTs) efficacy patients diagnosed with ASD up 11/06/2024. The outcomes were measured by total Responsiveness Scale (SRS) scores Repetitive Behavior (RBS). Results This meta-analysis ultimately included 12 RCTs 498 patients. In an initial analysis, intranasal showed no significant effect impairments. For high dose 48 IU per day, beneficial found. According dose–response meta-analysis, results indicated that higher doses might be more effective for Depending behaviors, overall analysis effect, while over day revealed suggested could Discussion Although these findings show consistent effects, suggest may ASD. Systematic review registration https://www.crd.york.ac.uk/prospero , identifier CRD42024567213.

Язык: Английский

Процитировано

0

Potential Therapeutic Effects of Ferula gummosa Boiss. Extract on Autistic-like Behaviors in Maternally Separated Mice: Role of NMDA receptor gene DOI Creative Commons

Forozan Yaghoubi,

Hossein Amini-Khoei, Kamal Solati

и другие.

Heliyon, Год журнала: 2025, Номер unknown, С. e42957 - e42957

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0

The relationship between serum thyroid hormone levels and symptoms severity in young children with autism DOI Creative Commons

Mária Kopčíková,

Barbara Rašková, Ivan Belica

и другие.

Endocrine Regulations, Год журнала: 2024, Номер 58(1)

Опубликована: Янв. 1, 2024

Abstract Objective. Autism spectrum disorders (ASD) are neurodevelopmental characterized by impaired social interaction and communication, restrictive repetitive patterns of behavior, interests activities. The aim this study was to determine the postnatal levels thyroid hor­mones investigate their association with severity ASD symptoms. Methods. included 56 children (46 boys 10 girls) aged 24–42 months. For diagnostics Diagnostic Observation Schedule - second version (ADOS-2) Interview-Revised (ADI-R) – interview child’s parents or guard­ians were used. Venous blood drawn right after diagnostic procedures analyze serum thyroid-stimulating hormone (s-TSH), free triiodothyronine (s-fT3), thyroxine (s-fT4) levels. Linear regression analysis conducted assess relationship between concentra­tions hormones symptoms severity. Results. Serum concentrations measured within normal reference ranges in almost all children. Decline s-TSH significantly associated an increase communication as rated a higher prevalence stereotyped behavior observed examination (ADOS-2). A decrease s-fT3 frequency assessed (ADI-R). Neither sex nor age significant predictors. Conclusion. Although normal, we demonstrated

Язык: Английский

Процитировано

1

Shank3 deficiency alters midbrain GABAergic neuron morphology, GABAergic markers and synaptic activity in primary striatal neurons DOI Creative Commons
Zuzana Bačová, Bohumila Jurkovičová-Tarabová, T. Havránek

и другие.

Molecular Brain, Год журнала: 2024, Номер 17(1)

Опубликована: Сен. 27, 2024

Abstract Abnormalities in gamma-aminobutyric acid (GABA)ergic neurotransmission play a role the pathogenesis of autism, although mechanisms responsible for alterations specific brain regions remain unclear. Deficits social motivation and interactions are core symptoms likely due to defects dopaminergic neural pathways. Therefore, investigating morphology functional roles GABAergic neurons within projection areas could elucidate underlying etiology autism. The aim this study was (1) compare arborization glutamate decarboxylase (GAD)-positive from midbrain tegmentum; (2) evaluate synaptic activity primary striatum; (3) assess postsynaptic puncta ventral striatum wild-type (WT) Shank3 -deficient mice. We found significant decrease number short neurites GAD positive tegmentum application blocker GABA A receptors (GABA R) revealed significantly increased frequency spontaneous currents (sPSCs) striatal compared their WT counterparts. mean absolute amplitude events higher also observed reduction gephyrin/GABA R γ2 colocalization adult male gene expression collybistin lower nucleus accumbens while gephyrin were tegmental area (VTA) Shank3- deficient In conclusion, deficiency leads impaired function areas. These changes may underlie autistic symptoms, potential interventions modulating pathways represent new treatment modality.

Язык: Английский

Процитировано

0