scholarly journals A pioneering study indicate role of GABRQ rs3810651 in ASD severity of Indo-Caucasoid female probands

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sharmistha Saha ◽  
Mahasweta Chatterjee ◽  
Swagata Sinha ◽  
Kanchan Mukhopadhyay
Keyword(s):  
Autism Spectrum ◽  
Activity Level ◽  
Gamma Aminobutyric Acid ◽  
Gene Encoding ◽  
Altered Expression ◽  
Inhibitory Neurotransmitter ◽  
Social And Emotional ◽  
Emotional Deficits ◽  
Stratified Analysis

AbstractAlteration in gamma aminobutyric acid (GABA), the principal inhibitory neurotransmitter, is speculated to be a potential risk factor for Autism Spectrum Disorder (ASD) due to an altered expression in the brain. Sensory, social, and emotional deficits of subjects with ASD were reported to be caused by an imbalance between excitatory and inhibitory neurotransmission as well as GABAergic dysfunction caused by inadequate receptor function. We for the first time studied association between ASD and a missense coding variant rs3810651 (I478F) in the GABRQ gene, encoding for one of the subunits of GABAA receptors. Stratified analysis on families with ASD probands (N = 251) and ethnically matched control subjects (N = 250) revealed marginally higher frequency of “A” allele and “AA” genotype in female ASD probands as compared to gender matched controls. Female probands demonstrated higher severity for Verbal communication (χ2 = 5.75, P = 0.01), Activity level (χ2 = 7.26, P  = 0.007), as well as Level and consistency of intellectual response (χ2 = 7.83 P = 0.005) in presence of “A/AA” warranting further in-depth investigation on the role of rs3810651 in ASD.

scholarly journals Is It Feasible of Prophylactic Alpha-5 GABA(A) Receptor Blockade for Preventing POCD?

2013 ◽  
Vol 3 (3) ◽  
pp. 61-62
Author(s):  
Fuzhou Wang
Keyword(s):  
Nervous System ◽  
General Anesthesia ◽  
Neuronal Excitability ◽  
Underlying Mechanism ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
Inhalational Anesthetics ◽  
Exploratory Data

GAMMA-AMINOBUTYRIC ACID (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system (CNS). It plays a role in regulating neuronal excitability throughout the nervous system. Also GABA activation is considered as the basis of general anesthesia including intravenous and inhalational anesthetics. Meanwhile, cumulating evidence indicated that GABA is the underlying mechanism of post-operative cognitive dysfunction (POCD). Based on these findings, researchers are beginning to focus on GABA as the target to treat POCD, but they ignored the role of GABA in the performance of general anesthesia, especially when the blockade of GABA was given prior to surgery. It is undoubtedly risking our patients in intra-operative awareness. Our exploratory data also verified our hypothesis in which the GABA inhibition would reduce the efficacy of inhalational anesthetics.

scholarly journals Interneuron Dysfunction and Inhibitory Deficits in Autism and Fragile X Syndrome

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2610
Author(s):  
Toshihiro Nomura
Keyword(s):  
Fragile X Syndrome ◽  
Therapeutic Potential ◽  
Fragile X ◽  
Single Gene ◽  
Autism Spectrum ◽  
Gamma Aminobutyric Acid ◽  
Inhibitory Neurotransmitter ◽  
Inhibitory Circuits ◽  
Inhibitory Deficits ◽  
Inhibitory Circuit

The alteration of excitatory–inhibitory (E–I) balance has been implicated in various neurological and psychiatric diseases, including autism spectrum disorder (ASD). Fragile X syndrome (FXS) is a single-gene disorder that is the most common known cause of ASD. Understanding the molecular and physiological features of FXS is thought to enhance our knowledge of the pathophysiology of ASD. Accumulated evidence implicates deficits in the inhibitory circuits in FXS that tips E–I balance toward excitation. Deficits in interneurons, the main source of an inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), have been reported in FXS, including a reduced number of cells, reduction in intrinsic cellular excitability, or weaker synaptic connectivity. Manipulating the interneuron activity ameliorated the symptoms in the FXS mouse model, which makes it reasonable to conceptualize FXS as an interneuronopathy. While it is still poorly understood how the developmental profiles of the inhibitory circuit go awry in FXS, recent works have uncovered several developmental alterations in the functional properties of interneurons. Correcting disrupted E–I balance by potentiating the inhibitory circuit by targeting interneurons may have a therapeutic potential in FXS. I will review the recent evidence about the inhibitory alterations and interneuron dysfunction in ASD and FXS and will discuss the future directions of this field.

The Role of Augmented E-Learning Systems for Enhancing Pro-Social Behaviour in Socially Impaired Individuals

2011 ◽  
pp. 248-272 ◽  
Author(s):  
Jonathan Bishop
Keyword(s):  
Assistive Technology ◽  
Cognitive Abilities ◽  
Emotional Functioning ◽  
Autism Spectrum ◽  
Learning Systems ◽  
Autism Spectrum Conditions ◽  
Social And Emotional ◽  
E Learning ◽  
Social Behaviours

E-learning systems generally rely on good visual and cognitive abilities, making them suitable for individuals with good levels of intelligence in these areas. A group of such individuals are those with non-systemising impairments (NSIs), such as people with autism spectrum conditions (ASCs). These individuals could benefit greatly from technology that allows them to use their abilities to overcome their impairments in social and emotional functioning in order to develop pro-social behaviours. Existing systems such as PARLE and MindReading are discussed, and a new one, the Visual Ontological Imitation System (VOIS), is proposed and discussed. This chapter details an investigation into the acceptability of these systems by those working in social work and advocacy. The study found that VOIS would be well received, although dependency on assistive technology and its impact on how others view NSIs still need to be addressed by society and its institutions.

scholarly journals Understanding intellectual disability and autism spectrum disorders from common mouse models: synapses to behaviour

Open Biology ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 180265 ◽  
Author(s):  
Vijaya Verma ◽  
Abhik Paul ◽  
Anjali Amrapali Vishwanath ◽  
Bhupesh Vaidya ◽  
James P. Clement
Keyword(s):  
Autism Spectrum Disorders ◽  
Intellectual Disability ◽  
Mouse Models ◽  
Autism Spectrum ◽  
Therapeutic Strategies ◽  
World Population ◽  
Normal Brain ◽  
Social And Emotional ◽  
Spectrum Disorders ◽  
Emotional Deficits

Normal brain development is highly dependent on the timely coordinated actions of genetic and environmental processes, and an aberration can lead to neurodevelopmental disorders (NDDs). Intellectual disability (ID) and autism spectrum disorders (ASDs) are a group of co-occurring NDDs that affect between 3% and 5% of the world population, thus presenting a great challenge to society. This problem calls for the need to understand the pathobiology of these disorders and to design new therapeutic strategies. One approach towards this has been the development of multiple analogous mouse models. This review discusses studies conducted in the mouse models of five major monogenic causes of ID and ASDs: Fmr1, Syngap1, Mecp2, Shank2/3 and Neuroligins/Neurnexins. These studies reveal that, despite having a diverse molecular origin, the effects of these mutations converge onto similar or related aetiological pathways, consequently giving rise to the typical phenotype of cognitive, social and emotional deficits that are characteristic of ID and ASDs. This convergence, therefore, highlights common pathological nodes that can be targeted for therapy. Other than conventional therapeutic strategies such as non-pharmacological corrective methods and symptomatic alleviation, multiple studies in mouse models have successfully proved the possibility of pharmacological and genetic therapy enabling functional recovery.

The GABA system and addiction

2018 ◽  
Author(s):  
David J. Nutt ◽  
Liam J. Nestor
Keyword(s):  
Potential Role ◽  
Abuse Liability ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Substance Addiction ◽  
Inhibitory Neurotransmitter ◽  
Gaba System ◽  
Clinical Potential ◽  
The Brain

Research points to the potential role of gamma-aminobutyric acid (GABA) in substance addiction. GABA is the major inhibitory neurotransmitter in the brain. Disturbances in the GABA system may predate substance abuse and addiction, whereby its efficacy to modulate other neurotransmitter systems (e.g. dopamine) strongly implicated in substance addiction behaviours is impaired. There are a number of addictive substances that boost GABA functioning, however, such as alcohol and benzodiazepines. Medications that boost the availability of GABA or mimic its effects at receptors may possess some clinical potential in treating addiction, but also have abuse liability.

The role of GABA in modulating the Xenopus electroretinogram

1997 ◽  
Vol 14 (6) ◽  
pp. 1143-1152 ◽  
Author(s):  
Arsaell Arnarsson ◽  
Thor Eysteinsson
Keyword(s):  
Light Sensitivity ◽  
Gaba Uptake ◽  
Peak Time ◽  
Gamma Aminobutyric Acid ◽  
Nipecotic Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
Retinal Circuitry ◽  
Gaba Antagonist

AbstractWe have recorded the electroretinogram (ERG) from the superfused eyecup of the Xenopus retina in order to assess the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and its agonists and antagonists, on individual ERG components. We found that GABA (0.5–10 mM) reduced the amplitudes of both the b- and d-waves of the Xenopus ERG. The GABA uptake blocker nipecotic acid (1 mM) had similar effects on b- and d-waves. GABA at 5 mM and 10 mM also caused an increase in the a-wave. The GABA antagonist picrotoxin (0.1–2 mM) and the GABA/a antagonist bicuculline (0.2 mM) both increased the amplitude of the b- and d-waves of the ERG. The GABA/b agonist baclofen (0.3 mM) reduced the amplitude of the ERG b-wave, enhanced the amplitude of the a-wave, and slightly reduced the amplitude and increased the peak time of the d-wave. The GABA/b antagonists phaclofen and saclofen had no reliable effects on the Xenopus ERG. Glutamate analogs known to affect specific types of retinal neurons were applied to modify the retinal circuitry and then the effects of GABA and its antagonists were examined under these modified conditions. 2-amino-4-phosphonobutyric acid (APB) increased the d-wave, and blocked the b-wave and the effect of GABA on the ERG, but not the antagonist-induced increase in the d-wave. KYN blocked the antagonist-induced increase in the b-wave, while GABA increases the amplitude of the b-wave if the d-wave has been removed by prior superfusion with kynurenic acid (KYN). N-methyl-DL-aspartate (NMDLA), which acts only in the proximal retina, reduced the amplitude of the ERG and blocked the effect of GABA and the antagonist-induced increase in ERG b- and d-waves amplitude. These results suggest that GABAergic mechanisms related to both A and B receptor types can influence the amplitude and light sensitivity of all the components of the Xenopus ERG. Since GABA is found in greatest abundance in the proximal retina, and B type of receptors are present almost exclusively there, the data suggests that most of the effects of GABA agonists and antagonists observed are dependent on proximal retinal mechanisms, and that there are separate mechanisms in the proximal retina related to the b- and the d-waves.

scholarly journals Role of DNA Methyl-CpG-Binding Protein MeCP2 in Rett Syndrome Pathobiology and Mechanism of Disease

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 75
Author(s):  
Shervin Pejhan ◽  
Mojgan Rastegar
Keyword(s):  
Rett Syndrome ◽  
Binding Protein ◽  
Autism Spectrum ◽  
Cellular Systems ◽  
De Novo Mutation ◽  
Genetic Mutations ◽  
Mecp2 Gene ◽  
Altered Expression ◽  
The Brain

Rett Syndrome (RTT) is a severe, rare, and progressive developmental disorder with patients displaying neurological regression and autism spectrum features. The affected individuals are primarily young females, and more than 95% of patients carry de novo mutation(s) in the Methyl-CpG-Binding Protein 2 (MECP2) gene. While the majority of RTT patients have MECP2 mutations (classical RTT), a small fraction of the patients (atypical RTT) may carry genetic mutations in other genes such as the cyclin-dependent kinase-like 5 (CDKL5) and FOXG1. Due to the neurological basis of RTT symptoms, MeCP2 function was originally studied in nerve cells (neurons). However, later research highlighted its importance in other cell types of the brain including glia. In this regard, scientists benefitted from modeling the disease using many different cellular systems and transgenic mice with loss- or gain-of-function mutations. Additionally, limited research in human postmortem brain tissues provided invaluable findings in RTT pathobiology and disease mechanism. MeCP2 expression in the brain is tightly regulated, and its altered expression leads to abnormal brain function, implicating MeCP2 in some cases of autism spectrum disorders. In certain disease conditions, MeCP2 homeostasis control is impaired, the regulation of which in rodents involves a regulatory microRNA (miR132) and brain-derived neurotrophic factor (BDNF). Here, we will provide an overview of recent advances in understanding the underlying mechanism of disease in RTT and the associated genetic mutations in the MECP2 gene along with the pathobiology of the disease, the role of the two most studied protein variants (MeCP2E1 and MeCP2E2 isoforms), and the regulatory mechanisms that control MeCP2 homeostasis network in the brain, including BDNF and miR132.

Examining the Role of Language in Play Among Children With and Without Developmental Disabilities

2020 ◽  
Vol 51 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Elizabeth J. Short ◽  
Rachael Cooper Schindler ◽  
Rita Obeid ◽  
Maia M. Noeder ◽  
Laura E. Hlavaty ◽  
...  
Keyword(s):  
Developmental Disabilities ◽  
Autism Spectrum ◽  
Free Play ◽  
Group Differences ◽  
Typically Developing ◽  
Play Skills ◽  
Critical Aspect ◽  
Hyperactivity Disorder ◽  
Better Than

Purpose Play is a critical aspect of children's development, and researchers have long argued that symbolic deficits in play may be diagnostic of developmental disabilities. This study examined whether deficits in play emerge as a function of developmental disabilities and whether our perceptions of play are colored by differences in language and behavioral presentations. Method Ninety-three children participated in this study (typically developing [TD]; n = 23, developmental language disorders [DLD]; n = 24, attention-deficit/hyperactivity disorder [ADHD]; n = 26, and autism spectrum disorder [ASD]; n = 20). Children were videotaped engaging in free-play. Children's symbolic play (imagination, organization, elaboration, and comfort) was scored under conditions of both audible language and no audible language to assess diagnostic group differences in play and whether audible language impacted raters' perception of play. Results Significant differences in play were evident across diagnostic groups. The presence of language did not alter play ratings for the TD group, but differences were found among the other diagnostic groups. When language was audible, children with DLD and ASD (but not ADHD) were scored poorly on play compared to their TD peers. When language was not audible, children with DLD were perceived to play better than when language was audible. Conversely, children with ADHD showed organizational deficits when language was not available to support their play. Finally, children with ASD demonstrated poor play performance regardless of whether language was audible or not. Conclusions Language affects our understanding of play skills in some young children. Parents, researchers, and clinicians must be careful not to underestimate or overestimate play based on language presentation. Differential skills in language have the potential to unduly influence our perceptions of play for children with developmental disabilities.

The Role of the SLP in Autism Spectrum Disorder Screening and Assessment

2008 ◽  
Vol 15 (2) ◽  
pp. 50-59 ◽  
Author(s):  
Amy Philofsky
Keyword(s):  
Language Development ◽  
Critical Role ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Children With Asd ◽  
Prevalence Estimates ◽  
Notable Increase ◽  
Screening Assessment ◽  
Critical Components

AbstractRecent prevalence estimates for autism have been alarming as a function of the notable increase. Speech-language pathologists play a critical role in screening, assessment and intervention for children with autism. This article reviews signs that may be indicative of autism at different stages of language development, and discusses the importance of several psychometric properties—sensitivity and specificity—in utilizing screening measures for children with autism. Critical components of assessment for children with autism are reviewed. This article concludes with examples of intervention targets for children with ASD at various levels of language development.

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