Regulation of Dietary Amino Acids and Voltage-Gated Calcium Channels in Autism Spectrum Disorder

2020 ◽  
pp. 647-660 ◽  
Author(s):  
Shubham Singh ◽  
Supraj Raja Sangam ◽  
Rajagopal Senthilkumar
Keyword(s):  
Amino Acids ◽  
Autism Spectrum Disorder ◽  
Calcium Channels ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Voltage Gated ◽  
Dietary Amino Acids ◽  
Voltage Gated Calcium Channels

scholarly journals A new homozygous CACNB2 mutation has functional relevance and supports a role for calcium channels in autism spectrum disorder

2019 ◽  
Author(s):  
Claudio Graziano ◽  
Patrick Despang ◽  
Flavia Palombo ◽  
Giulia Severi ◽  
Annio Posar ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Calcium Channels ◽  
Calcium Channel ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Site Directed Mutagenesis ◽  
Global Developmental Delay ◽  
Whole Cell ◽  
Voltage Gated ◽  
Voltage Gated Calcium Channels

Abstract BackgroundDiagnostic yield in patients with autism spectrum disorder (ASD) has improved over the last years, thanks to the introduction of whole genome arrays and next generation sequencing, but etiology is still unknown for the majority of cases. Among distinct cellular pathways, evidence implicating dysregulation of cellular calcium homeostasis in ASD pathogenesis has been accumulating, and specific mutations in voltage-gated calcium channels found in patients with autism were shown to be functionally relevant.MethodsWhole exome sequencing and Sanger sequencing were performed to identify and confirm variants in a girl with ASD, global developmental delay and precocious puberty, born of first-degree cousins. Site-directed mutagenesis was used to generate a human CaVβ2d calcium channel subunit carrying a CACNB2 mutation. Whole-cell patch-clamp recordings were performed to reveal functional effects of mutant CaVβ2d on Ba2+-currents mediated by L-type (CaV1.2) calcium channels in transiently transfected HEK-293 cells.ResultsIn an ASD patient, we identified a rare homozygous variant (p.Arg70Cys) in the CACNB2 gene coding for the auxiliary CaVβ2subunit of voltage-gated calcium channels. In a recombinant system, the CaVβ2 variant, which was not previously associated to ASD, was found to alter CaV1.2 calcium channel function by significantly affecting activation and inactivation of whole-cell Ba2+-currents.LimitationsAlthough the evidence of CACNB2 involvement in ASD is slowly accumulating, the number of reported patients is very limited. Deep clinical phenotyping and functional studies in larger sets of subjects will be instrumental to fully understand the penetrance and outcome of CACNB2 variants.ConclusionsThe p.Arg70Cys variant in CACNB2 shows functional consequences similar to other ASD-associated CaVβ2 mutations. These results support the idea of CACNB2 variations contributing to the development of ASD and hint to a rare form of Mendelian recessive autism with possible specific comorbidities.

Decreased levels of urinary free amino acids in children with autism spectrum disorder

2018 ◽  
Vol 54 ◽  
pp. 45-49 ◽  
Author(s):  
Chen Li ◽  
Kangwei Shen ◽  
Lanling Chu ◽  
Ping Liu ◽  
Yuan Song ◽  
...  
Keyword(s):  
Amino Acids ◽  
Autism Spectrum Disorder ◽  
Free Amino Acids ◽  
Free Amino ◽  
Children With Autism ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Investigating plasma amino acids for differentiating individuals with autism spectrum disorder and typically developing peers

2018 ◽  
Vol 50 ◽  
pp. 60-72 ◽  
Author(s):  
Troy Vargason ◽  
Uwe Kruger ◽  
Deborah L. McGuinness ◽  
James B. Adams ◽  
Elizabeth Geis ◽  
...  
Keyword(s):  
Amino Acids ◽  
Autism Spectrum Disorder ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Plasma Amino Acids ◽  
Typically Developing

scholarly journals Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

2019 ◽  
Author(s):  
Arturo Andrade ◽  
Ashton Brennecke ◽  
Shayna Mallat ◽  
Julian Brown ◽  
Juan Gomez-Rivadeneira ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Psychiatric Disorders ◽  
Emotional Disorders ◽  
Autism Spectrum ◽  
Genetic Associations ◽  
Voltage Gated ◽  
Functional Studies ◽  
Voltage Gated Calcium Channels ◽  
Neuronal Processes ◽  
Function Expression

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is key for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools and databases to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. We will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

scholarly journals Genetic Associations between Voltage-Gated Calcium Channels and Psychiatric Disorders

2019 ◽  
Vol 20 (14) ◽  
pp. 3537 ◽  
Author(s):  
Arturo Andrade ◽  
Ashton Brennecke ◽  
Shayna Mallat ◽  
Julian Brown ◽  
Juan Gomez-Rivadeneira ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Psychiatric Disorders ◽  
Emotional Disorders ◽  
Autism Spectrum ◽  
Genetic Associations ◽  
Voltage Gated ◽  
Functional Studies ◽  
Voltage Gated Calcium Channels ◽  
Neuronal Processes ◽  
Function Expression

Psychiatric disorders are mental, behavioral or emotional disorders. These conditions are prevalent, one in four adults suffer from any type of psychiatric disorders world-wide. It has always been observed that psychiatric disorders have a genetic component, however, new methods to sequence full genomes of large cohorts have identified with high precision genetic risk loci for these conditions. Psychiatric disorders include, but are not limited to, bipolar disorder, schizophrenia, autism spectrum disorder, anxiety disorders, major depressive disorder, and attention-deficit and hyperactivity disorder. Several risk loci for psychiatric disorders fall within genes that encode for voltage-gated calcium channels (CaVs). Calcium entering through CaVs is crucial for multiple neuronal processes. In this review, we will summarize recent findings that link CaVs and their auxiliary subunits to psychiatric disorders. First, we will provide a general overview of CaVs structure, classification, function, expression and pharmacology. Next, we will summarize tools to study risk loci associated with psychiatric disorders. We will examine functional studies of risk variations in CaV genes when available. Finally, we will review pharmacological evidence of the use of CaV modulators to treat psychiatric disorders. Our review will be of interest for those studying pathophysiological aspects of CaVs.

Development of Neural Structure and Function in Autism Spectrum Disorder: Potential Implications for Learning Language

2020 ◽  
Vol 29 (4) ◽  
pp. 1783-1797
Author(s):  
Kelly L. Coburn ◽  
Diane L. Williams
Keyword(s):  
Autism Spectrum Disorder ◽  
Language Development ◽  
Diffusion Tensor ◽  
Autism Spectrum ◽  
Language Intervention ◽  
Spectrum Disorder ◽  
Autistic Children ◽  
Neural Structure ◽  
Complex Information ◽  
And Function

Purpose Neurodevelopmental processes that begin during gestation and continue throughout childhood typically support language development. Understanding these processes can help us to understand the disruptions to language that occur in neurodevelopmental conditions, such as autism spectrum disorder (ASD). Method For this tutorial, we conducted a focused literature review on typical postnatal brain development and structural and functional magnetic resonance imaging, diffusion tensor imaging, magnetoencephalography, and electroencephalography studies of the neurodevelopmental differences that occur in ASD. We then integrated this knowledge with the literature on evidence-based speech-language intervention practices for autistic children. Results In ASD, structural differences include altered patterns of cortical growth and myelination. Functional differences occur at all brain levels, from lateralization of cortical functions to the rhythmic activations of single neurons. Neuronal oscillations, in particular, could help explain disrupted language development by elucidating the timing differences that contribute to altered functional connectivity, complex information processing, and speech parsing. Findings related to implicit statistical learning, explicit task learning, multisensory integration, and reinforcement in ASD are also discussed. Conclusions Consideration of the neural differences in autistic children provides additional scientific support for current recommended language intervention practices. Recommendations consistent with these neurological findings include the use of short, simple utterances; repetition of syntactic structures using varied vocabulary; pause time; visual supports; and individualized sensory modifications.

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