C1q as a Regulator of Brain Development: Implications for Autism Spectrum Disorders

Fang, Cenxiao; Garbuzova‐Davis, Svitlana; Tan, Jun; Obregon, Demian

doi:10.4172/2168-975x.1000152

Cited by 4 publications

(2 citation statements)

References 68 publications

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“…The expression of most complement proteins is up-regulated in the periphery of autistic patients, suggesting that the complement pathway may be activated in the periphery of autistic patients. However, the expression trends of complement proteins in the brain of autistic patient are not completely consistent 34,35 . On the other hand, beyond its involvement with innate immune responses, complement proteins has been increasingly implicated in playing an important role in neurodevelopment, including neurogenesis, neuronal migration, and synaptic remodeling [34][35][36] .…”

Section: Discussionmentioning

confidence: 97%

“…However, the expression trends of complement proteins in the brain of autistic patient are not completely consistent 34,35 . On the other hand, beyond its involvement with innate immune responses, complement proteins has been increasingly implicated in playing an important role in neurodevelopment, including neurogenesis, neuronal migration, and synaptic remodeling [34][35][36] . Together, the changes in the complement system in peripheral blood, PBMCs, and brain of ASD patients highlights that this system may play a key role in the pathogenesis of ASD and is worthy of further study.…”

Section: Discussionmentioning

confidence: 97%

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A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

Shen¹,

Zhang²,

Lin³

et al. 2021

Preprint

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Background: Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces significant challenges due to the existence of heterogeneity. Methods: In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out. Results: The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, PBMCs, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focus on several common and previously reported mechanisms of ASD. Limitations: The number of samples carrying risk genes in omics research is limited. In further research, a large sample size is required. A group of children who have been diagnosed with ASD but have not been detected to carry risk genes should also be included.Conclusion: The biomarkers for ASD diagnosis could be found by taking DEPs and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 97%

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

Shen¹,

Zhang²,

Lin³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

et al. 2022

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Background: Autism spectrum disorder (ASD) has become one of the most common neurological developmental disorders in children. However, the study of ASD diagnostic markers faces signi cant challenges due to the existence of heterogeneity.Methods: In this study, genetic testing was performed on children who were clinically diagnosed with ASD. Children with ASD susceptibility genes and healthy controls were studied. The proteomics of plasma and peripheral blood mononuclear cells (PBMCs) as well as plasma metabolomics were carried out.Results: The results showed that although there was genetic heterogeneity in children with ASD, the differentially expressed proteins (DEPs) in plasma, PBMCs, and differential metabolites in plasma could still effectively distinguish autistic children from controls. The mechanism associated with them focus on several common and previously reported mechanisms of ASD.Limitations: The number of samples carrying risk genes in omics research is limited. In further research, a large sample size is required. A group of children who have been diagnosed with ASD but have not been detected to carry risk genes should also be included. Conclusion:The biomarkers for ASD diagnosis could be found by taking DEPs and differential metabolites into consideration. Integrating omics data, glycerophospholipid metabolism and N-glycan biosynthesis might play a critical role in the pathogenesis of ASD.

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Maternal genetics influences fetal neurodevelopment and postnatal autism spectrum disorder-like phenotype by modulating in-utero immunosuppression

Jaini

Wolf

et al. 2021

Transl Psychiatry

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Genetic studies in ASD have mostly focused on the proband, with no clear understanding of parental genetic contributions to fetal neurodevelopment. Among parental etiological factors, perinatal maternal inflammation secondary to autoimmunity, infections, and toxins is associated with ASD. However, the inherent impact of maternal genetics on in-utero inflammation and fetal neurodevelopment in the absence of strong external inflammatory exposures is not known. We used the PtenWT/m3m4 mouse model for ASD to demonstrate the impact of maternal genetics on the penetrance of ASD-like phenotypes in the offspring. PtenWT/m3m4 (Momm3m4) or PtenWT/WT (MomWT) females, their offspring, and placental interface were analyzed for inflammatory markers, gene expression, and cellular phenotypes at E17.5. Postnatal behavior was tested by comparing pups from Momm3m4 vs. MomWT. Mothers of the PtenWT/m3m4 genotype (Momm3m4) showed inadequate induction of IL-10 mediated immunosuppression during pregnancy. Low IL-10 in the mother was directly correlated with decreased complement expression in the fetal liver. Fetuses from Momm3m4 had increased breakdown of the blood–brain–barrier, neuronal loss, and lack of glial cell maturation during in-utero stages. This impact of maternal genotype translated to a postnatal increase in the risk of newborn mortality, visible macrocephaly and ASD-like repetitive and social behaviors. Depending on maternal genotype, non-predisposed (wildtype) offspring showed ASD-like phenotypes, and phenotypic penetrance was decreased in predisposed pups from MomWT. Our study introduces the concept that maternal genetics alone, without any added external inflammatory insults, can modulate fetal neurodevelopment and ASD-related phenotypes in the offspring via alteration of IL-10 mediated materno-fetal immunosuppression.

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C1q as a Regulator of Brain Development: Implications for Autism Spectrum Disorders

Cited by 4 publications

References 68 publications

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

A Combined Proteomics and Metabolomics Profiling to Investigate the Genetic Heterogeneity of Autistic Children

Maternal genetics influences fetal neurodevelopment and postnatal autism spectrum disorder-like phenotype by modulating in-utero immunosuppression

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