Activation of the 5-HT1A Receptor by Eltoprazine Restores Mitochondrial and Motor Deficits in a Model of Fragile X Syndrome.

Neurons rely on mitochondrial energy metabolism for essential functions like neurogenesis, neurotransmission, and synaptic plasticity. Mitochondrial dysfunctions are associated with neurodevelopmental disorders including Fragile X syndrome (FXS), the most common cause of inherited intellectual disability, which also presents with motor skill deficits. However, the precise role of mitochondria in the pathophysiology of FXS remains largely unknown.

The effects of prolonged pacifier use on language development in infants and toddlers.

Pacifiers are a common soothing tool used by parents to calm and comfort infants and toddlers. While pacifiers can provide temporary relief, there is growing concern about the potential long-term effects of prolonged pacifier use on language and cognitive development. Previous studies have suggested that prolonged use of pacifiers may have negative consequences on language outcomes in infants and toddlers, especially during the first few years of life known to be a critical period for language development.

Intellectual Disability and Behavioral Deficits Linked to CYFIP1 Missense Variants Disrupting Actin Polymerization.

Background: 15q11.2 deletions and duplications have been linked to autism spectrum disorder, schizophrenia, and intellectual disability. Recent evidence suggests that dysfunctional CYFIP1 (cytoplasmic FMR1 interacting protein 1) contributes to the clinical phenotypes observed in individuals with 15q11.

Dynamic Interplay between Social Brain Development and Nutrient Intake in Young Children.

Myelination of the brain structures underlying social behavior in humans is a dynamic process that parallels the emergence of social-emotional development and social skills in early life. Of the many genetic and environmental factors regulating the myelination processes, nutrition is considered as a critical and modifiable early-life factor for establishing healthy social brain networks. However, the impact of nutrition on the longitudinal development of social brain myelination remains to be fully understood.

SREBP modulates the NADP/NADPH cycle to control night sleep in Drosophila.

Sleep behavior is conserved throughout evolution, and sleep disturbances are a frequent comorbidity of neuropsychiatric disorders. However, the molecular basis underlying sleep dysfunctions in neurological diseases remains elusive. Using a model for neurodevelopmental disorders (NDDs), the Drosophila Cytoplasmic FMR1 interacting protein haploinsufficiency (Cyfip), we identify a mechanism modulating sleep homeostasis.

Modelling Learning and Memory in Drosophila to Understand Intellectual Disabilities.

Neurodevelopmental disorders (NDDs) include a large number of conditions such as Fragile  X  syndrome, autism spectrum disorders and Down syndrome, among others. They are characterized by limitations in adaptive and social behaviors, as well as intellectual disability (ID). Whole-exome and whole-genome sequencing studies have highlighted a large number of NDD/ID risk genes.

Aralar Sequesters GABA into Hyperactive Mitochondria, Causing Social Behavior Deficits.

Social impairment is frequently associated with mitochondrial dysfunction and altered neurotransmission. Although mitochondrial function is crucial for brain homeostasis, it remains unknown whether mitochondrial disruption contributes to social behavioral deficits. Here, we show that Drosophila mutants in the homolog of the human CYFIP1, a gene linked to autism and schizophrenia, exhibit mitochondrial hyperactivity and altered group behavior.

Conserved Tao Kinase Activity Regulates Dendritic Arborization, Cytoskeletal Dynamics, and Sensory Function in .

Dendritic arborization is highly regulated and requires tight control of dendritic growth, branching, cytoskeletal dynamics, and ion channel expression to ensure proper function. Abnormal dendritic development can result in altered network connectivity, which has been linked to neurodevelopmental disorders, including autism spectrum disorders (ASDs). How neuronal growth control programs tune dendritic arborization to ensure function is still not fully understood.

Domain-Specific Cognitive Impairments in Humans and Flies With Reduced CYFIP1 Dosage.

Background: Deletions encompassing a four-gene region on chromosome 15 (BP1-BP2 at 15q11.2), seen at a population frequency of 1 in 500, are associated with increased risk for schizophrenia, epilepsy, and other common neurodevelopmental disorders. However, little is known in terms of how these common deletions impact cognition.

Mitochondrial dysfunction in Autism Spectrum Disorder: clinical features and perspectives.

Autism Spectrum Disorder (ASD) is a prototypic pervasive developmental disorder characterized by social interaction, and communication deficits, repetitive, stereotypic patterns of behavior, and impairments in language and development. Clinical studies have identified mitochondrial disturbances at the levels of DNA, activity, complexes, oxidative stress, and metabolites in blood and urine of ASD patients. However, these observations from postmortem brains or peripheral tissues do not provide a direct link between autism and mitochondria.

Learning and behavioral deficits associated with the absence of the fragile X mental retardation protein: what a fly and mouse model can teach us.

The Fragile X syndrome (FXS) is the most frequent form of inherited mental disability and is considered a monogenic cause of autism spectrum disorder. FXS is caused by a triplet expansion that inhibits the expression of the FMR1 gene. The gene product, the Fragile X Mental Retardation Protein (FMRP), regulates mRNA metabolism in brain and nonneuronal cells.

Learning and memory deficits consequent to reduction of the fragile X mental retardation protein result from metabotropic glutamate receptor-mediated inhibition of cAMP signaling in Drosophila.

Loss of the RNA-binding fragile X protein [fragile X mental retardation protein (FMRP)] results in a spectrum of cognitive deficits, the fragile X syndrome (FXS), while aging individuals with decreased protein levels present with a subset of these symptoms and tremor. The broad range of behavioral deficits likely reflects the ubiquitous distribution and multiple functions of the protein. FMRP loss is expected to affect multiple neuronal proteins and intracellular signaling pathways, whose identity and interactions are essential in understanding and ameliorating FXS symptoms.

Selective serotonin reuptake inhibitors for the treatment of hypersensitive esophagus: a randomized, double-blind, placebo-controlled study.

Objectives: Ambulatory 24-h pH-impedance monitoring can be used to assess the relationship of persistent symptoms and reflux episodes, despite proton pump inhibitor (PPI) therapy. Using this technique, we aimed to identify patients with hypersensitive esophagus and evaluate the effect of selective serotonin reuptake inhibitors (SSRIs) on their symptoms.

Methods: Patients with normal endoscopy and typical reflux symptoms (heartburn, chest pain, and regurgitation), despite PPI therapy twice daily, underwent 24-h pH-impedance monitoring.