scholarly journals Modulation of Serotonin Receptors in Neurodevelopmental Disorders: Focus on 5-HT7 Receptor

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3348
Author(s):  
Jieon Lee ◽  
Diana Avramets ◽  
Byungsun Jeon ◽  
Hyunah Choo
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Fragile X ◽  
Autism Spectrum ◽  
Neuronal Morphology ◽  
Point Of View ◽  
Receptor Subtype ◽  
Potential Therapeutic Target

Since neurodevelopmental disorders (NDDs) influence more than 3% of children worldwide, there has been intense investigation to understand the etiology of disorders and develop treatments. Although there are drugs such as aripiprazole, risperidone, and lurasidone, these medications are not cures for the disorders and can only help people feel better or alleviate their symptoms. Thus, it is required to discover therapeutic targets in order to find the ultimate treatments of neurodevelopmental disorders. It is suggested that abnormal neuronal morphology in the neurodevelopment process is a main cause of NDDs, in which the serotonergic system is emerging as playing a crucial role. From this point of view, we noticed the correlation between serotonin receptor subtype 7 (5-HT7R) and NDDs including autism spectrum disorder (ASD), fragile X syndrome (FXS), and Rett syndrome (RTT). 5-HT7R modulators improved altered behaviors in animal models and also affected neuronal morphology via the 5-HT7R/G12 signaling pathway. Through the investigation of recent studies, it is suggested that 5-HT7R could be a potential therapeutic target for the treatment of NDDs.

scholarly journals Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study

2021 ◽  
Vol 22 (6) ◽  
pp. 2863
Author(s):  
James Robert Brašić ◽  
Ayon Nandi ◽  
David S. Russell ◽  
Danna Jennings ◽  
Olivier Barret ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Fragile X Syndrome ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Fragile X ◽  
Single Gene ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Receptor Subtype ◽  
Metabotropic Glutamate

Multiple lines of evidence suggest that dysfunction of the metabotropic glutamate receptor subtype 5 (mGluR5) plays a role in the pathogenesis of autism spectrum disorder (ASD). Yet animal and human investigations of mGluR5 expression provide conflicting findings about the nature of dysregulation of cerebral mGluR5 pathways in subtypes of ASD. The demonstration of reduced mGluR5 expression throughout the living brains of men with fragile X syndrome (FXS), the most common known single-gene cause of ASD, provides a clue to examine mGluR5 expression in ASD. We aimed to (A) compare and contrast mGluR5 expression in idiopathic autism spectrum disorder (IASD), FXS, and typical development (TD) and (B) show the value of positron emission tomography (PET) for the application of precision medicine for the diagnosis and treatment of individuals with IASD, FXS, and related conditions. Two teams of investigators independently administered 3-[18F]fluoro-5-(2-pyridinylethynyl)benzonitrile ([18F]FPEB), a novel, specific mGluR5 PET ligand to quantitatively measure the density and the distribution of mGluR5s in the brain regions, to participants of both sexes with IASD and TD and men with FXS. In contrast to participants with TD, mGluR5 expression was significantly increased in the cortical regions of participants with IASD and significantly reduced in all regions of men with FXS. These results suggest the feasibility of this protocol as a valuable tool to measure mGluR5 expression in clinical trials of individuals with IASD and FXS and related conditions.

A Comparative Study of Sociability in Angelman, Cornelia de Lange, Fragile X, Down and Rubinstein Taybi Syndromes and Autism Spectrum Disorder

2016 ◽  
Vol 121 (6) ◽  
pp. 465-486 ◽  
Author(s):  
Joanna Moss ◽  
Lisa Nelson ◽  
Laurie Powis ◽  
Jane Waite ◽  
Caroline Richards ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Down Syndrome ◽  
Intellectual Disability ◽  
Fragile X Syndrome ◽  
Neurodevelopmental Disorders ◽  
Fragile X ◽  
Selective Mutism ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Cornelia De Lange

Abstract Few comparative studies have evaluated the heterogeneity of sociability across a range of neurodevelopmental disorders. The Sociability Questionnaire for People with Intellectual Disability (SQID) was completed by caregivers of individuals with Cornelia de Lange (n = 98), Angelman (n = 66), Fragile X (n = 142), Down (n = 117) and Rubinstein Taybi (n = 88) syndromes and autism spectrum disorder (ASD; n = 107). Between groups and age-band (<12yrs; 12–18yrs; >18yrs) comparisons of SQID scores were conducted. Rates of behaviors indicative of selective mutism were also examined. Fragile X syndrome achieved the lowest SQID scores. Cornelia de Lange, ASD, and Fragile X groups scored significantly lower than Angelman, Down and Rubinstein Taybi groups. Selective mutism characteristics were highest in Cornelia de Lange (40%) followed by Fragile X (17.8%) and ASD (18.2%). Age-band differences were identified in Cornelia de Lange and Down syndrome.

Neurodevelopmental Disorders

2020 ◽  
pp. 387-401
Author(s):  
Althea Robinson Shelton ◽  
Jessica Duis ◽  
Beth Malow
Keyword(s):  
Autism Spectrum Disorder ◽  
Neurodevelopmental Disorders ◽  
Diagnostic Tests ◽  
Sleep Disturbances ◽  
Sleep Problems ◽  
Fragile X ◽  
Clinical History ◽  
Autism Spectrum ◽  
Prader Willi Syndrome ◽  
Typically Developing

Compared to typically developing children, sleep disturbances are exceedingly prevalent in children with neurodevelopmental disorders. The diagnostic criteria for many neurodevelopmental disorders includes sleep problems. Sleep disturbance in this population is often multifactorial and caused by the interplay of genetic, neurobiological and environmental overlap. These disturbances often present either as insomnia or hypersomnia. Different sleep disorders present with these complaints and based on the clinical history and findings from diagnostic tests, an appropriate diagnosis can be made. The chapter covers autism spectrum disorder, Down syndrome, Prader–Willi syndrome, Angelman syndrome, Rett syndrome, Fragile X syndrome, Williams syndrome, and Smith–Magenis syndrome.

scholarly journals Local Protein Translation and RNA Processing of Synaptic Proteins in Autism Spectrum Disorder

2021 ◽  
Vol 22 (6) ◽  
pp. 2811
Author(s):  
Yuyoung Joo ◽  
David R. Benavides
Keyword(s):  
Autism Spectrum Disorder ◽  
Fragile X ◽  
Single Gene ◽  
Protein Translation ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Spectrum Disorder ◽  
Synaptic Proteins ◽  
Local Translation ◽  
Translation Control

Autism spectrum disorder (ASD) is a heritable neurodevelopmental condition associated with impairments in social interaction, communication and repetitive behaviors. While the underlying disease mechanisms remain to be fully elucidated, dysfunction of neuronal plasticity and local translation control have emerged as key points of interest. Translation of mRNAs for critical synaptic proteins are negatively regulated by Fragile X mental retardation protein (FMRP), which is lost in the most common single-gene disorder associated with ASD. Numerous studies have shown that mRNA transport, RNA metabolism, and translation of synaptic proteins are important for neuronal health, synaptic plasticity, and learning and memory. Accordingly, dysfunction of these mechanisms may contribute to the abnormal brain function observed in individuals with autism spectrum disorder (ASD). In this review, we summarize recent studies about local translation and mRNA processing of synaptic proteins and discuss how perturbations of these processes may be related to the pathophysiology of ASD.

scholarly journals Living-Cell Diffracted X-ray Tracking Analysis Confirmed Internal Salt Bridge Is Critical for Ligand-Induced Twisting Motion of Serotonin Receptors

2021 ◽  
Vol 22 (10) ◽  
pp. 5285
Author(s):  
Kazuhiro Mio ◽  
Shoko Fujimura ◽  
Masaki Ishihara ◽  
Masahiro Kuramochi ◽  
Hiroshi Sekiguchi ◽  
...  
Keyword(s):  
Serotonin Receptors ◽  
Serotonin Receptor ◽  
Frame Rate ◽  
Receptor Subtype ◽  
Transmembrane Segment ◽  
Hek 293 ◽  
Gold Nanocrystals ◽  
X Ray ◽  
Time Dynamics ◽  
Analytical Technique

Serotonin receptors play important roles in neuronal excitation, emotion, platelet aggregation, and vasoconstriction. The serotonin receptor subtype 2A (5-HT2AR) is a Gq-coupled GPCR, which activate phospholipase C. Although the structures and functions of 5-HT2ARs have been well studied, little has been known about their real-time dynamics. In this study, we analyzed the intramolecular motion of the 5-HT2AR in living cells using the diffracted X-ray tracking (DXT) technique. The DXT is a very precise single-molecular analytical technique, which tracks diffraction spots from the gold nanocrystals labeled on the protein surface. Trajectory analysis provides insight into protein dynamics. The 5-HT2ARs were transiently expressed in HEK 293 cells, and the gold nanocrystals were attached to the N-terminal introduced FLAG-tag via anti-FLAG antibodies. The motions were recorded with a frame rate of 100 μs per frame. A lifetime filtering technique demonstrated that the unliganded receptors contain high mobility population with clockwise twisting. This rotation was, however, abolished by either a full agonist α-methylserotonin or an inverse agonist ketanserin. Mutation analysis revealed that the “ionic lock” between the DRY motif in the third transmembrane segment and a negatively charged residue of the sixth transmembrane segment is essential for the torsional motion at the N-terminus of the receptor.

Sign in / Sign up

Export Citation Format

Share Document