Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs

Plummer, Prue N.; Colson, Natalie Jane; Lewohl, Joanne Marie; MacKay, Rachel K.; Fernandez, Francesca; Haupt, Larisa M.; Griffiths, Lyn R.

doi:10.1016/j.gene.2011.08.031

Cited by 25 publications

(14 citation statements)

References 36 publications

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“…In SGZ, GABA is also involved in the control of the number of actively proliferating neural stem cells (NSCs) during neurogenesis via GABAergic interneurons (Masiulis et al, 2011). Interestingly, GABA A receptor subunit 3 as well as GABBR2 were found to be expressed at lower levels in leukocytes of patients with migraines compared to healthy controls (Plummer et al, 2011), and a polymorphism in GABRA3 was associated with altered pharmacological treatment response of epilepsy patients (Hung et al, 2013). ADCY1 has not previously been identified as a target of hsa-miR-212-3p (Fig.…”

Section: Discussionmentioning

confidence: 99%

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Haenisch¹,

Zhao²,

Chhibber³

et al. 2015

Neurobiology of Disease

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MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally control the expression of their target genes via RNA interference. There is increasing evidence that expression of miRNAs is dysregulated in neuronal disorders, including epilepsy, a chronic neurological disorder characterized by spontaneous recurrent seizures. Mesial temporal lobe epilepsy (MTLE) is a common type of focal epilepsy in which disease-induced abnormalities of hippocampal neurogenesis in the subgranular zone as well as gliosis and neuronal cell loss in the cornu ammonis area are reported. We hypothesized that in MTLE altered miRNA-mediated regulation of target genes could be involved in hippocampal cell remodeling. A miRNA screen was performed in hippocampal focal and non-focal brain tissue samples obtained from the temporal neocortex (both n=8) of MTLE patients. Out of 215 detected miRNAs, two were differentially expressed (hsa-miR-34c-5p: mean increase of 5.7 fold (p=0.014), hsa-miR-212-3p: mean decrease of 76.9% (p=0.0014)). After in-silico target gene analysis and filtering, reporter gene assays confirmed RNA interference for hsa-miR-34c-5p with 3′-UTR sequences of GABRA3, GRM7 and GABBR2 and for hsa-miR-212-3p with 3′-UTR sequences of SOX11, MECP2, ADCY1 and ABCG2. Reporter gene assays with mutated 3′-UTR sequences of the transcription factor SOX11 identified two different binding sites for hsa-miR-212-3p and its primary transcript partner hsa-miR-132-3p. Additionally, there was an inverse time-dependent expression of Sox11 and miR-212-3p as well as miR-132-3p in rat neonatal cortical neurons. Transfection of neurons with anti-miRs for miR-212-3p and miR-132-3p suggest that both miRNAs work synergistically to control Sox11 expression. Taken together, these results suggest that differential miRNA expression in neurons could contribute to an altered function of the transcription factor SOX11 and other genes in the setting of epilepsy, resulting not only in impaired neural differentiation, but also in imbalanced neuronal excitability and accelerated drug export.

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Section: Discussionmentioning

confidence: 99%

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Haenisch¹,

Zhao²,

Chhibber³

et al. 2015

Neurobiology of Disease

View full text Add to dashboard Cite

show abstract

“…Given the inaccessibility of brain tissue for analysis, this concept of developing a marker from peripheral blood for central neurologic diseases or treatments has been widely explored. For example, microarray analysis has demonstrated unique patterns of differentially expressed genes in peripheral blood mononuclear cells associated with amyotrophic lateral sclerosis, migraines, and schizophrenia (23,24). Altered methylation of neuropsychiatric genes in DNA obtained from blood in patients with borderline personality disorder has been demonstrated (25).…”

Section: Discussionmentioning

confidence: 99%

Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies

White

Brost

Sun

et al. 2013

Hypertension in Pregnancy

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ObjectiveTo compare genome-wide methylation profiles in maternal leukocyte DNA between normotensive and preeclamptic pregnant women at delivery.MethodsAge, body mass index matched case-control comparison of methylation at 27,578 cytosine—guanine sites in 14,495 genes in maternal leukocyte DNA in women with preeclampsia (PE; n = 14) and normotensive controls (n = 14).ResultsPE was associated with widespread differential methylation favoring hypermethylation. Pathway analysis identified the best matched process as a neuropeptide signaling pathway (p < 10−5); best matched disease as eclampsia (p < 9.97 × 10−20). Significantly differentially methylated genes (GRIN2b. GABRA1. PCDHB7, and BEX1) are associated with seizures.ConclusionAltered maternal leukocyte DNA methylation is associated with PE at delivery, and differential methylation of certain neuronal genes may explain the risk for eclampsia.

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“…Plummer et al [49] performed a study aiming to assess the GABA A R genes’ expression profile in migraineurs and controls. The study demonstrated that GABRA3 was significantly down regulated in female patients compared with controls which could result in a decrease of GABA A R activation.…”

Section: Discussionmentioning

confidence: 99%

Interaction between γ-Aminobutyric Acid A Receptor Genes: New Evidence in Migraine Susceptibility

et al. 2013

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Migraine is a common neurological episodic disorder with a female-to-male prevalence 3- to 4-fold higher, suggesting a possible X-linked genetic component. Our aims were to assess the role of common variants of gamma-aminobutyric acid A receptor (GABAAR) genes, located in the X-chromosome, in migraine susceptibility and the possible interaction between them. An association study with 188 unrelated cases and 286 migraine-free controls age- and ethnic matched was performed. Twenty-three tagging SNPs were selected in three genes (GABRE, GABRA3 and GABRQ). Allelic, genotypic and haplotypic frequencies were compared between cases and controls. We also focused on gene-gene interactions. The AT genotype of rs3810651 of GABRQ gene was associated with an increased risk for migraine (OR: 4.07; 95% CI: 1.71-9.73, p=0.002), while the CT genotype of rs3902802 (OR: 0.41; 95% CI: 0.21-0.78, p=0.006) and GA genotype of rs2131190 of GABRA3 gene (OR: 0.53; 95% CI: 0.32-0.88, p=0.013) seem to be protective factors. All associations were found in the female group and maintained significance after Bonferroni correction. We also found three nominal associations in the allelic analyses although there were no significant results in the haplotypic analyses. Strikingly, we found strong interactions between six SNPs encoding for different subunits of GABAAR, all significant after permutation correction. To our knowledge, we show for the first time, the putative involvement of polymorphisms in GABAAR genes in migraine susceptibility and more importantly we unraveled a role for novel gene-gene interactions opening new perspectives for the development of more effective treatments.

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Significant differences in gene expression of GABA receptors in peripheral blood leukocytes of migraineurs

Cited by 25 publications

References 36 publications

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

SOX11 identified by target gene evaluation of miRNAs differentially expressed in focal and non-focal brain tissue of therapy-resistant epilepsy patients

Genome-wide methylation profiling demonstrates hypermethylation in maternal leukocyte DNA in preeclamptic compared to normotensive pregnancies

Interaction between γ-Aminobutyric Acid A Receptor Genes: New Evidence in Migraine Susceptibility

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