Dlg4 and Vamp2 are involved in comorbid epilepsy and attention-deficit hyperactivity disorder: A microarray data study

Xi, Xiao-Jun; Tang, Jihong; Zhang, Bingbing; Xiao, Xiao; Hu, Xiaoyue; Wan, Yu Mui; Zhou, Cheng; Lin, Hong

doi:10.1016/j.yebeh.2020.107192

Cited by 7 publications

(6 citation statements)

References 34 publications

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“…Thus, it is undoubtfully a fast and effective method to develop novel therapeutic targets by exploring shared molecular mechanisms of epilepsy and comorbid conditions [7]. There have been several studies show the shared molecular mechanisms of epilepsy and neuropsychiatric comorbidities, such as GABRA4, FZD7, Dlg4, and Vamp2 [10][11][12]. However, the association of epilepsy and digestive comorbidities are still unclear.…”

Section: Introductionmentioning

confidence: 99%

Potential Novel Therapeutic Targets In Epilepsy From The View of Intestinal Comorbidities - Inflammatory Bowel Disease

Song

2021

Preprint

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Background: Epilepsy is a complicated neurological disorder with almost 30% refractory. Recent years, several studies showed that epilepsy is associated with its comorbidities by shared molecular mechanisms. However, the association of epilepsy and digestive comorbidities are still unclear. In this study, we aim to explore the association between inflammatory bowel disease (IBD) and epilepsy, and to find promising therapeutic targets for refractory epilepsy. Methods: Two gene expression profiles (GSE134697 and GSE59071) were selected from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by GEO2R and the DESeq2 package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of intersection DEGs and Gene Set Enrichment Analysis (GSEA) were conducted by clusterProfiler package. The protein-protein interactions (PPI) network was established by using STRING and visualized by Cytoscape. Genes in the most significant module identified by MCODE plug-in were considered as candidate hub genes. Validation of hub genes were performed by using the GSE143272 dataset. Results: Cytokine-cytokine receptor interaction pathway is identified as a communal pathway between IBD and epilepsy. CXCL8, CXCR4 and ITGAX were identified as the hub genes. Conclusions: The identification of the communal pathway and hub genes in this study contributes to a potential novel therapeutic target in refractory epilepsy.

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Section: Introductionmentioning

confidence: 99%

Potential Novel Therapeutic Targets In Epilepsy From The View of Intestinal Comorbidities - Inflammatory Bowel Disease

Song

2021

Preprint

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“…Hong et al [30], on the contrary, examined the Homer protein, which is a PSD protein located in the postsynaptic region of glutamatergic excitatory synapses, on an ADHD animal model and reported that the expression of Homer 1a and Homer 2a/b genes, which encode the Homer protein, was lower in the ADHD group. Xi et al [33] observed that the DLG4 gene, which encodes the PSD95 protein, was less expressed than that in the control group in their study on children with ADHD. The results of this study suggested that PSD95, a PSD protein, might be effective in the pathogenesis of ADHD.…”

Section: Discussionmentioning

confidence: 94%

Role of Glutamate Receptor-related Biomarkers in the Etiopathogenesis of ADHD

Ulu

Demirci

Şener

et al. 2023

Clin Psychopharmacol Neurosci

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Objective: Pathways associated with glutamate receptors are known to play a role in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). However, cyclin-dependent kinase 5 (CDK5), microtubule-associated protein-2 (MAP2), guanylate kinase-associated protein (GKAP), and postsynaptic density 95 (PSD95), all of which are biomarkers involved in neurodevelopmental processes closely related to glutamatergic pathways, have not previously been studied in patients with ADHD. The main purpose of this study was to evaluate the plasma levels of CDK5, MAP2, GKAP, and PSD95 in children with ADHD and investigate whether these markers have a role in the etiology of ADHD. Methods: Ninety-six children with ADHD between 6 and 15 years of age and 72 healthy controls were included in the study. Five milliliters of blood samples were taken from all participants. The samples were stored at −80°C until analyzed by the enzyme-linked immunosorbent assay method. Results: Statistically significantly lower CDK5 levels were observed in children with ADHD than in healthy controls (p = 0.037). The MAP2, GKAP, and PSD95 levels were found to be statistically significantly higher in the ADHD group than in healthy controls (p = 0.012, p = 0.009, and p = 0.024, respectively). According to binary regression analysis, CDK5 and MAP2 levels were found to be predictors of ADHD. Conclusion: In conclusion, we found that a close relationship existed between ADHD and glutamatergic pathways, and low levels of CDK5 and high levels of MAP2 and GKAP played a role in the etiopathogenesis of ADHD.

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“…A reduction in VAMP2 gene expression in the hippocampus and entorhinal cortex has also been demonstrated in patients with Alzheimer's disease, with levels correlating with the degree of cognitive dysfunction [Sze et al, 2000]. Downregulation of VAMP2 gene expression has also been implicated in patients with comorbid epilepsy and ADHD [Xi et al, 2020].…”

Section: Discussionmentioning

confidence: 99%

VAMP2 Gene-Related Neurodevelopmental Disorder: A Differential Diagnosis for Rett/Angelman-Type Spectrum of Disorders

Bogue¹,

Ryan²,

Wassmer³

et al. 2023

Mol Syndromol

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Introduction: VAMP2 is an instrumental protein in neuronal synaptic transmission in the brain, facilitating neurotransmitter release. It is encoded by the VAMP2 gene, and pathogenic variants in this gene cause neurodevelopmental features including early onset axial hypotonia, intellectual disability, and features of autism spectrum disorder. To date, only three types of allelic variants (loss of function, in-frame deletions, and missense variants) in the VAMP2 gene have been previously reported in 11 patients with learning difficulties. Here, we describe a patient in whom a novel de novo pathogenic variant in the VAMP2 gene was identified. Case Presentation: A 15-month-old girl presented with early onset hypotonia, global developmental delay, learning difficulties, microcephaly, nystagmus, strabismus, and stereotypies. Later, she developed a sleep disorder, challenging behaviour with self-injury, and scoliosis. Gene agnostic analysis of whole genome sequencing data identified a novel de novo heterozygous missense variant c.197G>C (p.Arg66Pro) in the VAMP2 gene SNARE motif region. Discussion: This is the fourth report describing VAMP2 gene-related neurodevelopmental disorder. This report adds to the genotype-phenotype correlation and highlights this condition as an important differential diagnosis of Rett/Angelman-type spectrum of disorders. Patients presenting with features of either Rett syndrome or Angelman syndrome, in whom genetic testing is not suggestive, should be evaluated for variants in the VAMP2 gene, given the significant overlap in clinical presentation of these disorders.

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Dlg4 and Vamp2 are involved in comorbid epilepsy and attention-deficit hyperactivity disorder: A microarray data study

Cited by 7 publications

References 34 publications

Potential Novel Therapeutic Targets In Epilepsy From The View of Intestinal Comorbidities - Inflammatory Bowel Disease

Potential Novel Therapeutic Targets In Epilepsy From The View of Intestinal Comorbidities - Inflammatory Bowel Disease

Role of Glutamate Receptor-related Biomarkers in the Etiopathogenesis of ADHD

VAMP2 Gene-Related Neurodevelopmental Disorder: A Differential Diagnosis for Rett/Angelman-Type Spectrum of Disorders

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