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

Singh, Simran Jeet; Sangam, Supraj Raja; Rajagopal, Senthilkumar

doi:10.1007/978-3-030-30402-7_24

Cited by 4 publications

(1 citation statement)

References 47 publications

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“…Autism spectrum disorder (ASD) is a complex and heritable neurodevelopmental condition, with a global prevalence of 0.62% ( 1 ). The prevalence of ASD is around 1% in China ( 2 ), while a higher prevalence rate is estimated to be 1 in 59 children in the USA ( 3 ). Although hundreds of genes have been found to be susceptible to ASD, the pathogenesis of ASD remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Wang

Qin

et al. 2022

Front. Immunol.

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Autism spectrum disorder (ASD) is a complex pervasive neurodevelopmental disorder and neuroinflammation may contribute to the pathogenesis of ASD. However, the exact mechanisms of abnormal release of proinflammatory mediators in ASD remain poorly understood. This study reports elevated plasma levels of the proinflammatory chemokine (C-C motif) ligand 5 (CCL5) in children with ASD, suggesting an aberrant inflammatory response appearing in the development of ASD. Mining of the expression data of brain or blood tissue from individuals with ASD reveals that mTOR signaling is aberrantly activated in ASD patients. Our in vitro study shows that suppression of mTOR reduces the gene expression and release of CCL5 from human microglia, supporting that CCL5 expression is regulated by mTOR activity. Furthermore, bacterial lipopolysaccharide (LPS)-induced CCL5 expression can be counteracted by siRNA against NF-κB, suggests a determining role of NF-κB in upregulating CCL5 expression. However, a direct regulatory relationship between the NF-κB element and the mTOR signaling pathway was not observed in rapamycin-treated cells. Our results show that the phosphorylated CREB can be induced to suppress CCL5 expression by outcompeting NF-κB in binding to CREB-binding protein (CREBBP) once the mTOR signaling pathway is inhibited. We propose that the activation of mTOR signaling in ASD may induce the suppression of phosphorylation of CREB, which in turn results in the increased binding of CREBBP to NF-κB, a competitor of phosphorylated CREB to drive expression of CCL5. Our study sheds new light on the inflammatory mechanisms of ASD and paves the way for the development of therapeutic strategy for ASD.

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Section: Introductionmentioning

confidence: 99%

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Wang

Qin

et al. 2022

Front. Immunol.

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Absolute quantitative analysis of endogenous neurotransmitters and amino acids by liquid chromatography-tandem mass spectrometry combined with multidimensional adsorption and collision energy defect

Shen

et al. 2021

Journal of Chromatography A

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Developmental Ambient Air Pollution Exposure in Mice Alters Fronto-Striatal Neurotransmitter System Function: Male-Biased Serotonergic Vulnerability

Cory-Slechta,

Conrad,

Marvin

et al. 2024

Atmosphere

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Air pollution (AP) exposures have been associated with autism (ASD), schizophrenia (SCZ), and attention deficit hyperactivity disorder (ADHD), male-biased neurodevelopmental disorders that are linked to alterations in brain fronto-striatal neurotransmitter systems. The current study sought to assess how developmental exposures of mice to inhaled ambient ultrafine particle (UFP) air pollution, considered its most reactive component, alters fronto-striatal functional correlations. Mice were exposed via inhalation to concentrated ambient UFPs from postnatal days (PND) 4–7 and 10–13. Frontal cortex, striatum, and serum were collected at PND14 and PND50 to evaluate both acute and persistent effects. UFP-induced changes, more extensive and persistent in males, included elimination of frontal cortical kynurenine correlations with striatal neurotransmitter function, persistent immunosuppression of approximately 50%, and striatal neurotransmitter turnover correlations with serum corticosterone. More limited effects in females did not show persistence. Collectively, these findings depict an apparently physiologically-integrated UFP-induced persistent male-biased vulnerability to brain fronto-striatal system dysfunction that could contribute to behavioral deficits associated with neurodevelopmental disorders. Further studies are needed to ascertain the interactive physiological mechanisms of male fronto-striatal vulnerability and their relation to behavioral impairments, mechanisms of apparent female compensation, and specific contaminants of AP that underlie this vulnerability.

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

Cited by 4 publications

References 47 publications

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

mTOR Signaling Pathway Regulates the Release of Proinflammatory Molecule CCL5 Implicated in the Pathogenesis of Autism Spectrum Disorder

Absolute quantitative analysis of endogenous neurotransmitters and amino acids by liquid chromatography-tandem mass spectrometry combined with multidimensional adsorption and collision energy defect

Developmental Ambient Air Pollution Exposure in Mice Alters Fronto-Striatal Neurotransmitter System Function: Male-Biased Serotonergic Vulnerability

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