Gene Expression Profiling in Cluster Headache: A Pilot Microarray Study

Sjöstrand, Christina; Duvefelt, Kristina; Steinberg, Anna; Remahl, Ingela Nilsson; Waldenlind, Elisabet; Hillert, J.

doi:10.1111/j.1526-4610.2006.00611.x

Cited by 22 publications

(28 citation statements)

References 51 publications

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“…The present study arises from a previous investigation into gene expression (measured with microarray analysis) by meningeal tissue after an experimental migraine attack (48). That study showed complex variations in gene expression patterns, possibly due to the choice of the tissue samples that included a heterogeneous peripheral district.…”

Section: Molecular Elements Involved In P2x 3 Gene Transcriptionmentioning

confidence: 99%

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Simonetti

Giniatullin

Fabbretti

2008

Journal of Biological Chemistry

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The molecular mechanisms underlying migraine pain remain unclear and probably require sustained facilitation in pain-sensing P2X 3 receptors gated by extracellular ATP in nociceptive sensory neurons. The major migraine mediator calcitonin generelated peptide (CGRP) is known to sensitize P2X 3 receptors to increase impulse flow to brainstem trigeminal nuclei. This process is mediated via changes in the expression and function of P2X 3 receptors initially through enhanced trafficking and, later, perhaps through augmented synthesis of P2X 3 receptors. To clarify the mechanisms responsible for CGRP-evoked long lasting alterations in P2X 3 receptors, we used as a model mouse trigeminal ganglion neurons in culture. CGRP activated Ca 2؉ -calmodulin-dependent kinase II, which became localized to the perimembrane region and neuronal processes, a phenomenon already apparent after 30 min and accompanied by a parallel increase in cAMP-response element-binding protein (CREB) phosphorylation and nuclear translocation. These effects triggered increased P2X 3 receptor transcription and were prevented by expressing a dominant negative form of CREB. Increased P2X 3 receptor synthesis was partly mediated by endogenous brain-derived neurotrophic factor (BDNF) because of its block by anti-BDNF antibodies and mimicry by exogenous BDNF. Immunocytochemistry experiments indicated distinct subpopulations of BDNF-or CGRP-sensitive trigeminal neurons with only partial overlap. The present data indicate a novel mechanism for enhancing P2X 3 receptor expression and function in trigeminal sensory neurons by CGRP via CREB phosphorylation. BDNF was an intermediate to extend the sensitizing effect of CGRP also to CGRP-insensitive neurons. This combinatorial action could serve as a powerful process to amplify and prolong pain mediated by P2X 3 receptors.Sensitization of sensory neurons represents the key phenomenon for generating chronic pain that remains relatively refractory to standard treatment (1). Current theories predict that chronic pain is brought about by a gain in the expression and function of sensory nociceptors that enhance their signal flow to the brain to ensure the long lasting nature of this process (2). Clarification of the novel gene expression profiles associated to pain should, therefore, be useful to target emerging molecules (and mechanisms) and for designing new analgesics. Previous studies (3) aimed at detecting changes in transcriptome patterns during pain conditions have provided only a limited description of the global alterations because of the complexity of pain pathologies and signal pathways.Migraine is a classical example of chronic, relapsing pain triggered by local release of endogenous pain mediators, such as the neuropeptide calcitonin gene-related peptide (CGRP) 2 (4, 5) that induces long lasting trigeminal neuronal sensitization (6) and novel gene transcription in sensory neurons (7-9). CGRPmediated signals are transduced at the cell membrane by activation of a G-protein-coupled receptor complex (composed b...

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Section: Molecular Elements Involved In P2x 3 Gene Transcriptionmentioning

confidence: 99%

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Simonetti

Giniatullin

Fabbretti

2008

Journal of Biological Chemistry

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“…Promising results were obtained for epilepsy16 and psychiatric1718 and neurodegenerative disorders1920212223, with gene expression differences similar to those observed in post-mortem brain material1920212223. Two gene expression profiling studies using microarray technology have been performed in cluster headache2425. In one, whole blood gene expression levels from three cluster headache patients and three controls were compared; 90 differentially expressed genes were identified, including upregulated calcium-binding proteins suggesting a possible role for non-infectious inflammation25.…”

mentioning

confidence: 98%

Identifying a gene expression signature of cluster headache in blood

Eising

Pelzer

Vijfhuizen

et al. 2017

Sci Rep

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Cluster headache is a relatively rare headache disorder, typically characterized by multiple daily, short-lasting attacks of excruciating, unilateral (peri-)orbital or temporal pain associated with autonomic symptoms and restlessness. To better understand the pathophysiology of cluster headache, we used RNA sequencing to identify differentially expressed genes and pathways in whole blood of patients with episodic (n = 19) or chronic (n = 20) cluster headache in comparison with headache-free controls (n = 20). Gene expression data were analysed by gene and by module of co-expressed genes with particular attention to previously implicated disease pathways including hypocretin dysregulation. Only moderate gene expression differences were identified and no associations were found with previously reported pathogenic mechanisms. At the level of functional gene sets, associations were observed for genes involved in several brain-related mechanisms such as GABA receptor function and voltage-gated channels. In addition, genes and modules of co-expressed genes showed a role for intracellular signalling cascades, mitochondria and inflammation. Although larger study samples may be required to identify the full range of involved pathways, these results indicate a role for mitochondria, intracellular signalling and inflammation in cluster headache.

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“…Therefore, we will confirm the clinical implications of these genes in a large cohort of cases. PTPRB has been reported to be a drug addiction-associated gene [21], and CREB5 to be upregulated in the blood of cases with cluster headaches when compared to controls [22]. High COL4A3 expression was found to correlate with poor prognosis after combined cisplatin-gemcitabine chemotherapy in non-small cell lung cancer, showing the discrepancy of biological functions of this gene in different tumors [23].…”

Section: Discussionmentioning

confidence: 99%

Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA

et al. 2014

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BackgroundmiRNAs play key regulatory roles in cellular pathological processes. We aimed to identify clinically meaningful biomarkers in pulmonary carcinoid tumors (PCTs), a member of neuroendocrine neoplasms, via profiling miRNAs and mRNAs.ResultsFrom the total of 1145 miRNAs, we obtained 16 and 17 miRNAs that showed positive and negative fold changes (FCs, tumors vs. normal tissues) in the top 1% differentially expressed miRNAs, respectively. We uncovered the target genes that were predicted by at least two prediction tools and overlapped by at least one-half of the top miRNAs, which yielded 44 genes (FC<-2) and 56 genes (FC>2), respectively. Higher expressions of CREB5, PTPRB and COL4A3 predicted favorable disease free survival (Hazard ratio: 0.03, 0.19 and 0.36; P value: 0.03, 0.03 and 0.08). Additionally, 79 mutated genes have been found in nine PCTs where TP53 was the only repeated mutation.ConclusionWe identified that the expressions of three genes have clinical implications in PCTs. The biological functions of these biomarkers warrant further studies.

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Gene Expression Profiling in Cluster Headache: A Pilot Microarray Study

Cited by 22 publications

References 51 publications

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Mechanisms Mediating the Enhanced Gene Transcription of P2X3 Receptor by Calcitonin Gene-related Peptide in Trigeminal Sensory Neurons

Identifying a gene expression signature of cluster headache in blood

Clinical biomarkers of pulmonary carcinoid tumors in never smokers via profiling miRNA and target mRNA

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