Changes in the gene expression profile during spontaneous migraine attacks.
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ABSTRACT:
SUBMITTER: Kogelman LJA
PROVIDER: S-EPMC8050061 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundStructural imaging has revealed changes in cortical thickness in migraine patients compared to healthy controls is reported, but presence of dynamic cortical and subcortical changes during migraine attack versus inter-ictal phase is unknown. The aim of the present study was to investigate possible changes in cortical thickness during spontaneous migraine attacks. We hypothesized that pain-related cortical area would be affected during the attack compared to an inter-ictal phase.MethodsTwenty-five patients with migraine without aura underwent three-dimensional T1-weighted imaging on a 3-Tesla MRI scanner during spontaneous and untreated migraine attacks. Subsequently, 20 patients were scanned in the inter-ictal phase, while 5 patients did not show up for the inter-ictal scan. Four patients were excluded from the analysis because of bilateral migraine pain and another one patient was excluded due to technical error in the imaging. Longitudinal image processing was done using FreeSurfer. Repeated measures ANOVA was used for statistical analysis and to control for multiple comparison the level of significance was set at p = 0.025.ResultsIn a total of 15 patients, we found reduced cortical thickness of the precentral (p = 0.023), pericalcarine (p = 0.024), and temporal pole (p = 0.017) cortices during the attack compared to the inter-ictal phase. Cortical volume was reduced in prefrontal (p = 0.018) and pericalcarine (p = 0.017) cortices. Hippocampus volume was increased during attack (p = 0.007). We found no correlations between the pain side or any other clinical parameters and the reduced cortical size.ConclusionSpontaneous migraine attacks are accompanied by transient reduced cortical thickness and volume in pain-related areas. The findings constitute a fingerprint of acute pain in migraine patients, which can be used as a possible biomarker to predict antimigraine treatment effect in future studies.Trial registrationThe study was registered at ClinicalTrials.gov ( NCT02202486 ).
| S-EPMC8380396 | biostudies-literature
Project description:Objective. To characterize changes in gene expression profile during human mature adipocyte dedifferentiation in ceiling culture. Methods. Subcutaneous (SC) and omental (OM) adipose tissue samples were obtained from 4 participants paired for age and BMI. Isolated adipocytes were dedifferentiated in ceiling culture. Gene expression analysis at days 0, 4, 7, and 12 of the cultures was performed using Affymetrix Human Gene 2.0 STvi arrays. Hierarchical clustering according to similarity of expression changes was used to identify overrepresented functions. Results. Four clusters gathered genes with similar expression between day 4 to day 7 but decreasing expression from day 7 to day 12. Most of these genes coded for proteins involved in adipocyte functions (LIPE, PLIN1, DGAT2, PNPLA2, ADIPOQ, CEBPA, LPL, FABP4, SCD, INSR, and LEP). Expression of several genes coding for proteins implicated in cellular proliferation and growth or cell cycle increased significantly from day 7 to day 12 (WNT5A, KITLG, and FGF5). Genes coding for extracellular matrix proteins were differentially expressed between days 0, 4, 7, and 12 (COL1A1, COL1A2, and COL6A3, MMP1, and TGFB1). Conclusion. Dedifferentiation is associated with downregulation of transcripts encoding proteins involved in mature adipocyte functions and upregulation of genes involved in matrix remodeling, cellular development, and cell cycle.
| S-EPMC5376413 | biostudies-literature
Project description:Information provided to patients is thought to influence placebo and drug effects. In a prospective, within-subjects, repeated-measures study of 66 subjects with episodic migraine, we investigated how variations in medication labeling modified placebo and drug effects. An initial attack with no treatment served as a control. In six subsequent migraine attacks, each participant received either placebo or Maxalt (10-mg rizatriptan) administered under three information conditions ranging from negative to neutral to positive (told placebo, told Maxalt or placebo, told Maxalt) (N = 459 documented attacks). Treatment order was randomized. Maxalt was superior to placebo for pain relief. When participants were given placebo labeled as (i) placebo, (ii) Maxalt or placebo, and (iii) Maxalt, the placebo effect increased progressively. Maxalt had a similar progressive boost when labeled with these three labels. The efficacies of Maxalt labeled as placebo and placebo labeled as Maxalt were similar. The efficacy of open-label placebo was superior to that of no treatment. Relative to no treatment, the placebo, under each information condition, accounted for more than 50% of the drug effect. Increasing "positive" information incrementally boosted the efficacy of both placebo and medication during migraine attacks. The benefits of placebo persisted even if placebo was honestly described. Whether treatment involves medication or placebo, the information provided to patients and the ritual of pill taking are important components of care.
| S-EPMC4005597 | biostudies-literature
Project description:In the field of headache disorders, the term "fear of attacks" refers to the fear of a headache attack occurring. Excessive fear of attacks may worsen the course of a migraine and lead to an increase in migraine activity. In the assessment of attack-related fear, a categorical (fear of attacks as a specific phobia) and a dimensional approach (measuring the extent of fear using a questionnaire) are available. The 29-item Fear of Attacks in Migraine Inventory (FAMI) is an economic self-report questionnaire for the assessment of attack-related fear, and it has good psychometric properties. The treatment of attack-related fear includes behavioral interventions as well as pharmacological therapy. Behavioral interventions have few side effects and are based on the treatment of common anxiety disorders (e.g., agoraphobia). Although the evidence of existing treatments is sparse, attack-related fear should be considered in routine care.
| S-EPMC10112828 | biostudies-literature
Project description:BackgroundAs the critical tissue of the central nervous system, the brain has been found to be involved in gonad development. Previous studies have suggested that gonadal fate may be affected by the brain. Identifying brain-specific molecular changes that occur during estrodiol-17β (E2) -induced feminization is crucial to our understanding of the molecular control of sex differentiation by the brains of fish.ResultsIn this study, the differential transcriptomic responses of the Takifugu rubripes larvae brain were compared after E2 treatment for 55 days. Our results showed that 514 genes were differentially expressed between E2-treated-XX (E-XX) and Control-XX (C-XX) T. rubripes, while 362 genes were differentially expressed between E2-treated-XY (E-XY) and Control-XY (C-XY). For example, the expression of cyp19a1b, gnrh1 and pgr was significantly up-regulated, while st, sl, tshβ, prl and pit-1, which belong to the growth hormone/prolactin family, were significantly down-regulated after E2 treatment, in both sexes. The arntl1, bhlbe, nr1d2, per1b, per3, cry1, cipc and ciart genes, which are involved in the circadian rhythm, were also found to be altered. Differentially expressed genes (DEGs), which were identified between E-XX and C-XX, were significantly enriched in neuroactive ligand-receptor interaction, arachidonic acid metabolism, cytokine-cytokine receptor interaction and the calcium signaling pathway. The DEGs that were identified between E-XY and C-XY were significantly enriched in tyrosine metabolism, phenylalanine metabolism, arachidonic acid metabolism and linoleic acid metabolism.ConclusionA number of genes and pathways were identified in the brain of E2-treated T. rubripes larvae by RNA-seq. It provided the opportunity for further study on the possible involvement of networks in the brain-pituitary-gonadal axis in sex differentiation in T. rubripes.
| S-EPMC8614003 | biostudies-literature
Project description:BackgroundThe decidua has been implicated in the "terminal pathway" of human term parturition, which is characterized by the activation of pro-inflammatory pathways in gestational tissues. However, the transcriptomic changes in the decidua leading to terminal pathway activation have not been systematically explored. This study aimed to compare the decidual expression of developmental signaling and inflammation-related genes before and after spontaneous term labor in order to reveal their involvement in this process.MethodsChorioamniotic membranes were obtained from normal pregnant women who delivered at term with spontaneous labor (TIL, n = 14) or without labor (TNL, n = 15). Decidual cells were isolated from snap-frozen chorioamniotic membranes with laser microdissection. The expression of 46 genes involved in decidual development, sex steroid and prostaglandin signaling, as well as pro- and anti-inflammatory pathways, was analyzed using high-throughput quantitative real-time polymerase chain reaction (qRT-PCR). Chorioamniotic membrane sections were immunostained and then semi-quantified for five proteins, and immunoassays for three chemokines were performed on maternal plasma samples.ResultsThe genes with the highest expression in the decidua at term gestation included insulin-like growth factor-binding protein 1 (IGFBP1), galectin-1 (LGALS1), and progestogen-associated endometrial protein (PAEP); the expression of estrogen receptor 1 (ESR1), homeobox A11 (HOXA11), interleukin 1? (IL1B), IL8, progesterone receptor membrane component 2 (PGRMC2), and prostaglandin E synthase (PTGES) was higher in TIL than in TNL cases; the expression of chemokine C-C motif ligand 2 (CCL2), CCL5, LGALS1, LGALS3, and PAEP was lower in TIL than in TNL cases; immunostaining confirmed qRT-PCR data for IL-8, CCL2, galectin-1, galectin-3, and PAEP; and no correlations between the decidual gene expression and the maternal plasma protein concentrations of CCL2, CCL5, and IL-8 were found.ConclusionsOur data suggests that with the initiation of parturition, the decidual expression of anti-inflammatory mediators decreases, while the expression of pro-inflammatory mediators and steroid receptors increases. This shift may affect downstream signaling pathways that can lead to parturition.
| S-EPMC5445200 | biostudies-literature
Project description:ObjectiveMigraine is a prevalent and disabling neurological disease. Its genesis is poorly understood, and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP).MethodsThirty-six migraine without aura patients were enrolled in a randomized, double-blind, 2-way, crossover, positive-controlled clinical trial study to receive infusion of an amylin analogue pramlintide or human αCGRP on 2 different experimental days. Furthermore, translational studies in cells and mouse models, and rat, mouse and human tissue samples were conducted.ResultsThirty patients (88%) developed headache after pramlintide infusion, compared to 33 (97%) after CGRP (p = 0.375). Fourteen patients (41%) developed migraine-like attacks after pramlintide infusion, compared to 19 patients (56%) after CGRP (p = 0.180). The pramlintide-induced migraine-like attacks had similar clinical characteristics to those induced by CGRP. There were differences between treatments in vascular parameters. Human receptor pharmacology studies showed that an amylin receptor likely mediates these pramlintide-provoked effects, rather than the canonical CGRP receptor. Supporting this, preclinical experiments investigating symptoms associated with migraine showed that amylin treatment, like CGRP, caused cutaneous hypersensitivity and light aversion in mice.InterpretationOur findings propose amylin receptor agonism as a novel contributor to migraine pathogenesis. Greater therapeutic gains could therefore be made for migraine patients through dual amylin and CGRP receptor antagonism, rather than selectively targeting the canonical CGRP receptor. ANN NEUROL 2021;89:1157-1171.
| S-EPMC8486152 | biostudies-literature
Project description:Na+/H+ exchanger 3 (NHE3) provides a major route for intestinal Na+ absorption. NHE3 has been considered a target of proinflammatory cytokines and enteropathogenic bacteria, and impaired NHE3 expression and/or activity may be responsible for inflammation-associated diarrhea. However, the possibility of loss of NHE3 function reciprocally affecting gut immune homeostasis has not been investigated. In this report, we describe that NHE3-deficient mice spontaneously develop colitis restricted to distal colonic mucosa. NHE3(-/-) mice housed in a conventional facility exhibited phenotypic features such as mild diarrhea, occasional rectal prolapse, and reduced body weight. Genomewide microarray analysis identified not only a large group of transport genes that potentially represent an adaptive response, but also a considerable number of genes consistent with an inflammatory response. Histological examination demonstrated changes in the distal colon consistent with active inflammation, including crypt hyperplasia with an increased number of 5-bromo-2'-deoxyuridine-positive cells, diffuse neutrophilic infiltrate with concomitant 15-fold increase in matrix metalloproteinase 8 expression, an increased number of pSer276-RelA-positive cells, and a significant decrease in periodic acid-Schiff-positive goblet cells. Real-time PCR demonstrated elevated expression of inducible nitric oxide synthase (38-fold), TNF-alpha (6-fold), macrophage inflammatory protein-2 (48-fold), and IL-18 (3-fold) in the distal colon of NHE3(-/-) mice. NHE3(-/-) mice showed enhanced bacterial adhesion and translocation in the distal colon. Colitis was ameliorated by oral administration of broad-spectrum antibiotics. In conclusion, NHE3 deficiency leads to an exacerbated innate immune response, an observation suggesting a potentially novel role of NHE3 as a modifier gene, which when downregulated during infectious or chronic colitis may modulate the extent and severity of colonic inflammation.
| S-EPMC2494721 | biostudies-literature
Project description:AimTo find out key genes responsible for hepatocarcinogenesis and to further understand the underlying molecular mechanism through investigating the differential gene expression between human normal liver tissue and hepatocellular carcinoma (HCC).MethodsDNA microarray was prepared by spotting PCR products of 1 000 human genes including 445 novel genes, 540 known genes as well as 12 positive (housekeeping) and 3 negative controls (plant gene) onto treated glass slides. cDNA probes were prepared by labeling normal liver tissue mRNA and cancer liver tissue mRNA with Cy3-dUTP and Cy5-dUTP separately through reverse transcription. The arrays were hybridized against the cDNA probe and the fluorescent signals were scanned. The data obtained from repeated experiments were analyzed.ResultsAmong the 20 couple samples investigated (from cancerous liver tissue and normal liver tissue), 38 genes including 21 novel genes and 17 known genes exhibited different expressions.ConclusioncDNA microarray technique is powerful to identify candidate target genes that may play important roles in human carcinogenesis. Further analysis of the obtained genes is helpful to understand the molecular changes in HCC progression and ultimately may lead to the identification of new targets for HCC diagnosis and intervention.
| S-EPMC4305923 | biostudies-literature
Project description:To address which mitochondria-related nuclear differentially expressed genes (DEGs) and related pathways are altered during human oocyte maturation, single-cell analysis was performed in three oocyte states: in vivo matured (M-IVO), in vitro matured (M-IVT), and failed to mature in vitro (IM-IVT). There were 691 DEGs and 16 mitochondria-related DEGs in the comparison of M-IVT vs. IM-IVT oocytes, and 2281 DEGs and 160 mitochondria-related DEGs in the comparison of M-IVT vs. M-IVO oocytes, respectively. The GO and KEGG analyses showed that most of them were involved in pathways such as oxidative phosphorylation, pyruvate metabolism, peroxisome, and amino acid metabolism, i.e., valine, leucine, isoleucine, glycine, serine, and threonine metabolism or degradation. During the progress of oocyte maturation, the metabolic pathway, which derives the main source of ATP, shifted from glucose metabolism to pyruvate and fatty acid oxidation in order to maintain a low level of damaging reactive oxygen species (ROS) production. Although the immature oocytes could be cultured to a mature stage by an in vitro technique (IVM), there were still some differences in mitochondria-related regulations, which showed that the mitochondria were regulated by nuclear genes to compensate for their developmental needs. Meanwhile, the results indicated that the current IVM culture medium should be optimized to compensate for the special need for further development according to this disclosure, as it was a latent strategy to improve the effectiveness of the IVM procedure.
| S-EPMC8774259 | biostudies-literature