Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates

DiCarlo, Gabriella E.; Wallace, Mark T.

doi:10.1016/j.neubiorev.2021.12.017

Cited by 13 publications

(13 citation statements)

References 324 publications

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“…Conditional knockout CSNK2B mice showed an age-dependent reduction in grip strength, impaired neuromuscular transmission, and inordinate synaptic gene expression ( Eiber et al, 2019 ). Abnormal emotional behavior, including autistic behavior, irritability, depression, and hyperactivity, may be associated with abnormalities in the CK2-mediated dopamine signaling pathway ( Rebholz et al, 2009 ; DiCarlo and Wallace, 2022 ). CK2 is also involved in signaling for a variety of developmental processes, such as embryogenesis and organogenesis ( Bandyopadhyay et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations

Zhang

Ye²,

Chen³

et al. 2022

Front. Neurosci.

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CSNK2B has recently been identified as the causative gene for Poirier–Bienvenu neurodevelopmental syndrome (POBINDS). POBINDS is a rare neurodevelopmental disorder characterized by early-onset epilepsy, developmental delay, hypotonia, and dysmorphism. Limited by the scarcity of patients, the genotype–phenotype correlations in POBINDS are still unclear. In the present study, we describe the clinical and genetic characteristics of eight individuals with POBINDS, most of whom suffered developmental delay, generalized epilepsy, and hypotonia. Minigene experiments confirmed that two intron variants (c.367+5G>A and c.367+6T>C) resulted in the skipping of exon 5, leading to a premature termination of mRNA transcription. Combining our data with the available literature, the types of POBINDS-causing variants included missense, nonsense, frameshift, and splicing, but the variant types do not reflect the clinical severity. Reduced casein kinase 2 holoenzyme activity may represent a unifying pathogenesis. We also found that individuals with missense variants in the zinc finger domain had manageable seizures (p = 0.009) and milder intellectual disability (p = 0.003) than those with missense variants in other domains of CSNK2B. This is the first study of genotype–phenotype correlations in POBINDS, drawing attention to the pathogenicity of intron variants and expanding the understanding of neurodevelopmental disorders.

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Section: Discussionmentioning

confidence: 99%

Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations

Zhang

Ye²,

Chen³

et al. 2022

Front. Neurosci.

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“…Sizable evidence points to a possible dysfunction within the dopamine system that may underlie ASD symptomatology [ 15 , 35 ]. Dopamine is the major catecholamine of the central nervous system and is involved in the regulation of a variety of functions, including locomotor activity and emotion, and affect motivated behavior and reward processing, all of which are affected in ASD.…”

Section: Discussionmentioning

confidence: 99%

“…Positron emission imaging studies in ASD patients have shown a significant reduction in prefrontal cortical levels of dopamine [ 30 ] and more recent MRI studies have shown several alterations in dopaminergic connectivity within the caudate nucleus in relation to ASD [ 31 , 32 , 33 ]. Interestingly, the extent of these alterations has been correlated with the severity of ASD symptoms [ 34 ] (also reviewed in [ 35 ]).…”

Section: Introductionmentioning

confidence: 99%

The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder

et al. 2022

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Autism Spectrum Disorder (ASD) is a progressive neurodevelopmental disorder mainly characterized by deficits in social communication and stereotyped behaviors and interests. Here, we aimed to investigate the state of several key players in the dopamine and glutamate neurotransmission systems in the valproic acid (VPA) animal model that was administered to E12.5 pregnant females as a single dose (450 mg/kg). We report no alterations in the number of mesencephalic dopamine neurons or in protein levels of tyrosine hydroxylase in either the striatum or the nucleus accumbens. In females prenatally exposed to VPA, levels of dopamine were slightly decreased while the ratio of DOPAC/dopamine was increased in the dorsal striatum, suggesting increased turn-over of dopamine tone. In turn, levels of D1 and D2 dopamine receptor mRNAs were increased in the nucleus accumbens of VPA mice suggesting upregulation of the corresponding receptors. We also report decreased protein levels of striatal parvalbumin and increased levels of p-mTOR in the cerebellum and the motor cortex of VPA mice. mRNA levels of mGluR1, mGluR4, and mGluR5 and the glutamate receptor subunits NR1, NR2A, and NR2B were not altered by VPA, nor were protein levels of NR1, NR2A, and NR2B and those of BDNF and TrkB. These findings are of interest as clinical trials aiming at the dopamine and glutamate systems are being considered.

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“…Interessanterweise ist nun beim Autismus beides der Fall. Nach einer im Februar 2022 erschienenen Publikation 29 fand man mittlerweile mehr als 1000 Gene, die mit ASD in Verbindung gebracht werden. Diese ständig wachsende Liste genetischer Faktoren – sowohl für einzelne seltene Syndrome mit einer genetischen Veränderung, die eine hohe Penetranz aufweist, als auch für viele Gene, die das Risiko für die Spektrum-Störung ASD jeweils nur geringgradig erhöhen – machte deutlich, dass es keine uniforme genetische Ursache und wahrscheinlich auch keinen uniformen biologischen Mechanismus für alle Störungen, die man bis vor Kurzem „Autismus“ genannt hat, gibt.…”

Section: Genetikunclassified

Autismus: Kindheit – Krankheit – Menschheit

Spitzer¹

2022

Nervenheilkunde

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Modeling dopamine dysfunction in autism spectrum disorder: From invertebrates to vertebrates

Cited by 13 publications

References 324 publications

Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations

Splicing Interruption by Intron Variants in CSNK2B Causes Poirier–Bienvenu Neurodevelopmental Syndrome: A Focus on Genotype–Phenotype Correlations

The State of the Dopaminergic and Glutamatergic Systems in the Valproic Acid Mouse Model of Autism Spectrum Disorder

Autismus: Kindheit – Krankheit – Menschheit

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