Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data

Dai, Si Yuan; Lin, Jingjing; Hou, Yanze; Luo, Xuerong; Shen, Yidong; Ou, Jianjun

doi:10.3389/fnmol.2023.1089871

Cited by 9 publications

(22 citation statements)

References 45 publications

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“…To date, although astrocytes and microglia actively respond to brain homeostasis aberration via activation, which is reflected in morphology change [33,34], most studies on ASD have focused on changes in the number of astroglia markers or the number of glial cells, rather than a thorough analysis of morphological changes in these cells [35]. Recent studies indicate that purine metabolism in glial cells seems to be the most strikingly disturbed pathway in autism [36], though, currently, nothing is known about whether the ASD-related imbalance also occurs at the receptor level. Moreover, despite the detailed role of glial cell function in ASD, little is known about the involvement of particular purinergic receptor subtypes in abnormalities of these cells.…”

Section: Introductionmentioning

confidence: 99%

Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders

et al. 2023

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Recent data suggest that defects in purinergic signalling are a common denominator of autism spectrum disorders (ASDs), though nothing is known about whether the disorder-related imbalance occurs at the receptor level. In this study, we investigated whether prenatal exposure to valproic acid (VPA) induces changes in purinergic receptor expression in adolescence and whether it corresponds to glial cell activation. Pregnant dams were subjected to an intraperitoneal injection of VPA at embryonic day 12.5. In the hippocampi of adolescent male VPA offspring, we observed an increase in the level of P2X1, with concomitant decreases in P2X7 and P2Y1 receptors. In contrast, in the cortex, the level of P2X1 was significantly reduced. Also, significant increases in cortical P2Y1 and P2Y12 receptors were detected. Additionally, we observed profound alterations in microglial cell numbers and morphology in the cortex of VPA animals, leading to the elevation of pro-inflammatory cytokine expression. The changes in glial cells were partially reduced via a single administration of a non-selective P2 receptor antagonist. These studies show the involvement of purinergic signalling imbalance in the modulation of brain inflammatory response induced via prenatal VPA exposure and may indicate that purinergic receptors are a novel target for pharmacological intervention in ASDs.

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Section: Introductionmentioning

confidence: 99%

Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders

et al. 2023

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“…Partial enzyme dysfunction may result in symptoms easily misdiagnosed as one of the many infantile syndromes characterized by neuropsychiatric, neuromotor, and neurosensorial impairments. In this regard, using metabolomic and transcriptomic approaches, dysfunctions of purine metabolism, other than the well-known ADSL deficiency, have been reported in autism spectrum disorders [ 304 , 305 ], such as a significant increase in ADA activity, with a reduction in UA [ 304 ], and an increase in hypoxanthine, inosine, and xanthosine [ 305 ]. Another reason for misdiagnosis is the occurrence of compensatory mechanisms, which may differ among individuals and may attenuate the effects of the purine inborn error, giving rise to various phenotypes that do not completely correlate with the genotype.…”

Section: Discussionmentioning

confidence: 99%

Inborn Errors of Purine Salvage and Catabolism

et al. 2023

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Cellular purine nucleotides derive mainly from de novo synthesis or nucleic acid turnover and, only marginally, from dietary intake. They are subjected to catabolism, eventually forming uric acid in humans, while bases and nucleosides may be converted back to nucleotides through the salvage pathways. Inborn errors of the purine salvage pathway and catabolism have been described by several researchers and are usually referred to as rare diseases. Since purine compounds play a fundamental role, it is not surprising that their dysmetabolism is accompanied by devastating symptoms. Nevertheless, some of these manifestations are unexpected and, so far, have no explanation or therapy. Herein, we describe several known inborn errors of purine metabolism, highlighting their unexplained pathological aspects. Our intent is to offer new points of view on this topic and suggest diagnostic tools that may possibly indicate to clinicians that the inborn errors of purine metabolism may not be very rare diseases after all.

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“…The combined multi‐omics approach has been reported in several studies of diagnostic markers for ASD 142,213,214 . For example, using metabolomic and transcriptomic approaches, Dai et al.…”

Section: Study On Diagnostic Biomarkers Of Asdmentioning

confidence: 99%

“…The combined multi-omics approach has been reported in several studies of diagnostic markers for ASD. 142,213,214 For example, using metabolomic and transcriptomic approaches, Dai et al revealed that blood uric acid levels were significantly lower in children with ASD and the expression levels of some genes related to purine metabolism differed between children with ASD and controls. 213 Integrated proteome and metabolome analysis, another study found that six signaling pathways were significantly enriched in ASD, three of which were correlated with impaired neuroinflammation (GSH metabolism, metabolism of xenobiotics by cytochrome P450, and transendothelial migration of leukocyte).…”

Section: The Identification Of Potential Biomarkers By Non-targeted O...mentioning

confidence: 99%

“…142,213,214 For example, using metabolomic and transcriptomic approaches, Dai et al revealed that blood uric acid levels were significantly lower in children with ASD and the expression levels of some genes related to purine metabolism differed between children with ASD and controls. 213 Integrated proteome and metabolome analysis, another study found that six signaling pathways were significantly enriched in ASD, three of which were correlated with impaired neuroinflammation (GSH metabolism, metabolism of xenobiotics by cytochrome P450, and transendothelial migration of leukocyte). 214 Although further validation is needed, in combination with proteomic and metabolomic data, a previous study suggests that glycerophospholipid metabolism and Nglycan biosynthesis may play a key role in the pathogenesis of ASD.…”

Section: The Identification Of Potential Biomarkers By Non-targeted O...mentioning

confidence: 99%

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Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

Zhuang,

Liang,

et al. 2024

MedComm

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Autism spectrum disorder (ASD) has become a common neurodevelopmental disorder. The heterogeneity of ASD poses great challenges for its research and clinical translation. On the basis of reviewing the heterogeneity of ASD, this review systematically summarized the current status and progress of pathogenesis, diagnostic markers, and interventions for ASD. We provided an overview of the ASD molecular mechanisms identified by multi‐omics studies and convergent mechanism in different genetic backgrounds. The comorbidities, mechanisms associated with important physiological and metabolic abnormalities (i.e., inflammation, immunity, oxidative stress, and mitochondrial dysfunction), and gut microbial disorder in ASD were reviewed. The non‐targeted omics and targeting studies of diagnostic markers for ASD were also reviewed. Moreover, we summarized the progress and methods of behavioral and educational interventions, intervention methods related to technological devices, and research on medical interventions and potential drug targets. This review highlighted the application of high‐throughput omics methods in ASD research and emphasized the importance of seeking homogeneity from heterogeneity and exploring the convergence of disease mechanisms, biomarkers, and intervention approaches, and proposes that taking into account individuality and commonality may be the key to achieve accurate diagnosis and treatment of ASD.

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Purine signaling pathway dysfunction in autism spectrum disorders: Evidence from multiple omics data

Cited by 9 publications

References 45 publications

Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders

Alterations of Purinergic Receptors Levels and Their Involvement in the Glial Cell Morphology in a Pre-Clinical Model of Autism Spectrum Disorders

Inborn Errors of Purine Salvage and Catabolism

Autism spectrum disorder: pathogenesis, biomarker, and intervention therapy

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