共查询到20条相似文献,搜索用时 15 毫秒
1.
Christoph Kraus Pia Baldinger Christina Rami-Mark Gregor Gryglewsky Georg S. Kranz Daniela Haeusler Andreas Hahn Wolfgang Wadsak Markus Mitterhauser Dan Rujescu Siegfried Kasper Rupert Lanzenberger 《PloS one》2014,9(9)
Background
The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) may impact on the in-vivo binding of important serotonergic structures such as the serotonin transporter (5-HTT) and the serotonin-1A (5-HT1A) receptor. Previous positron emission tomography (PET) studies on the association between Val66Met and 5-HTT and 5-HT1A binding potential (BPND) have demonstrated equivocal results.Methods
We conducted an imaging genetics study investigating the effect of Val66Met genotype on 5-HTT or 5-HT1A BPND in 92 subjects. Forty-one subjects (25 healthy subjects and 16 depressive patients) underwent genotyping for Val66Met and PET imaging with the 5-HTT specific radioligand [11C]DASB. Additionally, in 51 healthy subjects Val66Met genotypes and 5-HT1A binding with the radioligand [carbonyl-11C]WAY-100635 were ascertained. Voxel-wise and region of interest-based analyses of variance were used to examine the influence of Val66Met on 5-HTT and 5-HT1A BPND.Results
No significant differences of 5-HTT nor 5-HT1A BPND between BDNF Val66Met genotype groups (val/val vs. met-carrier) were detected. There was no interaction between depression and Val66Met genotype status.Conclusion
In line with previous data, our work confirms an absent effect of BDNF Val66Met on two major serotonergic structures. These results could suggest that altered protein expression associated with genetic variants, might be compensated in vivo by several levels of unknown feedback mechanisms. In conclusion, Val66Met genotype status is not associated with changes of in-vivo binding of 5-HTT and 5-HT1A receptors in human subjects. 相似文献2.
Hugh Ramsay Ian Kelleher Padraig Flannery Mary C. Clarke Fionnuala Lynch Michelle Harley Dearbhla Connor Carol Fitzpatrick Derek W. Morris Mary Cannon 《PloS one》2013,8(11)
Objective
Psychotic experiences occur at a much greater prevalence in the population than psychotic disorders. There has been little research to date, however, on genetic risk for this extended psychosis phenotype. We examined whether COMT or BDNF genotypes were associated with psychotic experiences or interacted with childhood trauma in predicting psychotic experiences.Method
Psychiatric interviews and genotyping for COMT-Val158Met and BDNF-Val66Met were carried out on two population-based samples of 237 individuals aged 11-15 years. Logistic regression was used to examine for main effects by genotype and childhood trauma, controlling for important covariates. This was then compared to a model with a term for interaction between genotype and childhood trauma. Where a possible interaction was detected, this was further explored in stratified analyses.Results
While childhood trauma showed a borderline association with psychotic experiences, COMT-Val158Met and BDNF-Val66Met genotypes were not directly associated with psychotic experiences in the population. Testing for gene x environment interaction was borderline significant in the case of COMT-Val158Met with individuals with the COMT-Val158Met Val-Val genotype, who had been exposed to childhood trauma borderline significantly more likely to report psychotic experiences than those with Val-Met or Met-Met genotypes. There was no similar interaction by BDNF-Val66Met genotype.Conclusion
The COMT-Val158Met Val-Val genotype may be a genetic moderator of risk for psychotic experiences in individuals exposed to childhood traumatic experiences. 相似文献3.
Background
The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia.Methods
Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements.Results
The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia.Conclusion
These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings. 相似文献4.
Background
The COMT Val158Met polymorphism modulates cortical dopaminergic catabolism, and predicts individual differences in prefrontal executive functioning in healthy adults and schizophrenic patients, and associates with EEG differences during sleep loss. We assessed whether the COMT Val158Met polymorphism was a novel marker in healthy adults of differential vulnerability to chronic partial sleep deprivation (PSD), a condition distinct from total sleep loss and one experienced by millions on a daily and persistent basis.Methodology/Principal Findings
20 Met/Met, 64 Val/Met, and 45 Val/Val subjects participated in a protocol of two baseline 10h time in bed (TIB) nights followed by five consecutive 4 h TIB nights. Met/Met subjects showed differentially steeper declines in non-REM EEG slow-wave energy (SWE)—the putative homeostatic marker of sleep drive—during PSD, despite comparable baseline SWE declines. Val/Val subjects showed differentially smaller increases in slow-wave sleep and smaller reductions in stage 2 sleep during PSD, and had more stage 1 sleep across nights and a shorter baseline REM sleep latency. The genotypes, however, did not differ in performance across various executive function and cognitive tasks and showed comparable increases in subjective and physiological sleepiness in response to chronic sleep loss. Met/Met genotypic and Met allelic frequencies were higher in whites than African Americans.Conclusions/Significance
The COMT Val158Met polymorphism may be a genetic biomarker for predicting individual differences in sleep physiology—but not in cognitive and executive functioning—resulting from sleep loss in a healthy, racially-diverse adult population of men and women. Beyond healthy sleepers, our results may also provide insight for predicting sleep loss responses in patients with schizophrenia and other psychiatric disorders, since these groups repeatedly experience chronically-curtailed sleep and demonstrate COMT-related treatment responses and risk factors for symptom exacerbation. 相似文献5.
Yi-Chen Hsieh Jiann-Shing Jeng Huey-Juan Lin Chaur-Jong Hu Chia-Chen Yu Li-Ming Lien Giia-Sheun Peng Chin-I Chen Sung-Chun Tang Nai-Fang Chi Hung-Pin Tseng Chang-Ming Chern Fang-I Hsieh Chyi-Huey Bai Yi-Rhu Chen Hung-Yi Chiou Formosa Stroke Genetic Consortium 《PloS one》2012,7(10)
Background
Endogenous estrogens play an important role in the overall cardiocirculatory system. However, there are no studies exploring the hormone metabolism and signaling pathway genes together on ischemic stroke, including sulfotransferase family 1E (SULT1E1), catechol-O-methyl-transferase (COMT), and estrogen receptor α (ESR1).Methods
A case-control study was conducted on 305 young ischemic stroke subjects aged ≦ 50 years and 309 age-matched healthy controls. SULT1E1 -64G/A, COMT Val158Met, ESR1 c.454−397 T/C and c.454−351 A/G genes were genotyped and compared between cases and controls to identify single nucleotide polymorphisms associated with ischemic stroke susceptibility. Gene-gene interaction effects were analyzed using entropy-based multifactor dimensionality reduction (MDR), classification and regression tree (CART), and traditional multiple regression models.Results
COMT Val158Met polymorphism showed a significant association with susceptibility of young ischemic stroke among females. There was a two-way interaction between SULT1E1 -64G/A and COMT Val158Met in both MDR and CART analysis. The logistic regression model also showed there was a significant interaction effect between SULT1E1 -64G/A and COMT Val158Met on ischemic stroke of the young (P for interaction = 0.0171). We further found that lower estradiol level could increase the risk of young ischemic stroke for those who carry either SULT1E1 or COMT risk genotypes, showing a significant interaction effect (P for interaction = 0.0174).Conclusions
Our findings support that a significant epistasis effect exists among estrogen metabolic and signaling pathway genes and gene-environment interactions on young ischemic stroke subjects. 相似文献6.
Rick Hursel Pilou L. H. R. Janssens Freek G. Bouwman Edwin C. Mariman Margriet S. Westerterp-Plantenga 《PloS one》2014,9(9)
Introduction
Green tea(GT) is able to increase energy expenditure(EE) and fat oxidation(FATox) via inhibition of catechol-O-methyl transferase(COMT) by catechins. However, this does not always appear unanimously because of large inter-individual variability. This may be explained by different alleles of the functional COMT Val108/158Met polymorphism that are associated with COMT enzyme activity; high-activity enzyme, COMTH(Val/Val genotype), and low-activity COMTL(Met/Met genotype).Methods
Fourteen Caucasian subjects (BMI: 22.2±2.3 kg/m2, age: 21.4±2.2 years) of whom 7 with the COMTH-genotype and 7 with the COMTL-genotype were included in a randomized, cross-over study in which EE and substrate oxidation were measured with a ventilated-hood system after decaffeinated GT and placebo(PL) consumption.Results
At baseline, EE, RQ, FATox and carbohydrate oxidation(CHOox) did not differ between groups. Significant interactions were observed between COMT genotypes and treatment for RQ, FATox and CHOox (p<0.05). After GT vs. PL, EE(GT: 62.2 vs. PL: 35.4 kJ.3.5 hrs; p<0.01), RQ(GT: 0.80 vs. PL: 0.83; p<0.01), FATox(GT: 18.3 vs. PL: 15.3 g/d; p<0.001) and CHOox(GT: 18.5 vs. PL: 24.3 g/d; p<0.001) were significantly different for subjects carrying the COMTH genotype, but not for subjects carrying the COMTL genotype (EE, GT: 60.3 vs. PL: 51.7 kJ.3.5 hrs; NS), (RQ, GT: 0.81 vs. PL: 0.81; NS), (FATox, GT: 17.3 vs. PL: 17.0 g/d; NS), (CHOox, GT: 22.1 vs. PL: 21.4 g/d; NS).Conclusion
Subjects carrying the COMTH genotype increased energy expenditure and fat-oxidation upon ingestion of green tea catechins vs, placebo, whereas COMTL genotype carriers reacted similarly to GT and PL ingestion. The differences in responses were due to the different responses on PL ingestion, but similar responses to GT ingestion, pointing to different mechanisms. The different alleles of the functional COMT Val108/158Met polymorphism appear to play a role in the inter-individual variability for EE and FATox after GT treatment.Trial Registration
Nederlands Trial register NTR1918 相似文献7.
Background
Reversible cerebral vasoconstriction syndrome (RCVS) could be complicated by cerebral ischemic events. Hypothetical mechanisms of RCVS involve endothelial dysfunction and sympathetic overactivity, both of which were reported to be related to brain-derived neurotrophic factor (BDNF). The study investigated the association between functional BDNF Val66Met polymorphism and RCVS.Methods
Patients with RCVS and controls were prospectively recruited and genotyped for the BDNF Val66Met polymorphism. Magnetic resonance angiography (MRA) and transcranial color-coded Doppler sonography were employed to evaluate cerebral vasoconstriction. Genotyping results, clinical parameters, vasoconstriction scores, mean flow velocities of the middle cerebral artery (VMCA), and Lindegaard indices were analyzed. Split-sample approach was employed to internally validate the data.Principal Findings
Ninety Taiwanese patients with RCVS and 180 age- and gender-matched normal controls of the same ethnicity completed the study. The genotype frequencies did not differ between patients and controls. Compared to patients with Met/Met homozygosity, patients with Val allele had higher mean vasoconstriction scores of all arterial segments (1.60±0.72 vs. 0.87±0.39, p<0.001), VMCA values (116.7±36.2 vs. 82.7±17.9 cm/s, p<0.001), and LI (2.41±0.91 vs. 1.89±0.41, p = 0.001). None of the Met/Met homozygotes, but 38.9% of the Val carriers, had VMCA values of >120 cm/s (p<0.001). Split-sample validation by randomization, age, entry time or residence of patients demonstrated concordant findings.Conclusions
Our findings link BDNF Val66Met polymorphism with the severity of RCVS for the first time and implicate possible pathogenic mechanisms for vasoconstriction in RCVS. 相似文献8.
Background
Recent data suggests that in chronic pain there are changes in gray matter consistent with decreased brain volume, indicating that the disease process may produce morphological changes in the brains of those affected. However, no study has evaluated cortical thickness in relation to specific functional changes in evoked pain. In this study we sought to investigate structural (gray matter thickness) and functional (blood oxygenation dependent level – BOLD) changes in cortical regions of precisely matched patients with chronic trigeminal neuropathic pain (TNP) affecting the right maxillary (V2) division of the trigeminal nerve. The model has a number of advantages including the evaluation of specific changes that can be mapped to known somatotopic anatomy.Methodology/Principal Findings
Cortical regions were chosen based on sensory (Somatosensory cortex (SI and SII), motor (MI) and posterior insula), or emotional (DLPFC, Frontal, Anterior Insula, Cingulate) processing of pain. Both structural and functional (to brush-induced allodynia) scans were obtained and averaged from two different imaging sessions separated by 2–6 months in all patients. Age and gender-matched healthy controls were also scanned twice for cortical thickness measurement. Changes in cortical thickness of TNP patients were frequently colocalized and correlated with functional allodynic activations, and included both cortical thickening and thinning in sensorimotor regions, and predominantly thinning in emotional regions.Conclusions
Overall, such patterns of cortical thickness suggest a dynamic functionally-driven plasticity of the brain. These structural changes, which correlated with the pain duration, age-at-onset, pain intensity and cortical activity, may be specific targets for evaluating therapeutic interventions. 相似文献9.
Jennifer O'Loughlin Marie-Pierre Sylvestre Aurélie Labbe Nancy C. Low Marie-Hélène Roy-Gagnon Erika N. Dugas Igor Karp James C. Engert 《PloS one》2014,9(12)
Background
While the heritability of cigarette smoking and nicotine dependence (ND) is well-documented, the contribution of specific genetic variants to specific phenotypes has not been closely examined. The objectives of this study were to test the associations between 321 tagging single-nucleotide polymorphisms (SNPs) that capture common genetic variation in 24 genes, and early smoking and ND phenotypes in novice adolescent smokers, and to assess if genetic predictors differ across these phenotypes.Methods
In a prospective study of 1294 adolescents aged 12–13 years recruited from ten Montreal-area secondary schools, 544 participants who had smoked at least once during the 7–8 year follow-up provided DNA. 321 single-nucleotide polymorphisms (SNPs) in 24 candidate genes were tested for an association with number of cigarettes smoked in the past 3 months, and with five ND phenotypes (a modified version of the Fagerstrom Tolerance Questionnaire, the ICD-10 and three clusters of ND symptoms representing withdrawal symptoms, use of nicotine for self-medication, and a general ND/craving symptom indicator).Results
The pattern of SNP-gene associations differed across phenotypes. Sixteen SNPs in seven genes (ANKK1, CHRNA7, DDC, DRD2, COMT, OPRM1, SLC6A3 (also known as DAT1)) were associated with at least one phenotype with a p-value <0.01 using linear mixed models. After permutation and FDR adjustment, none of the associations remained statistically significant, although the p-values for the association between rs557748 in OPRM1 and the ND/craving and self-medication phenotypes were both 0.076.Conclusions
Because the genetic predictors differ, specific cigarette smoking and ND phenotypes should be distinguished in genetic studies in adolescents. Fifteen of the 16 top-ranked SNPs identified in this study were from loci involved in dopaminergic pathways (ANKK1/DRD2, DDC, COMT, OPRM1, and SLC6A3).Impact
Dopaminergic pathways may be salient during early smoking and the development of ND. 相似文献10.
Karling P Danielsson Å Wikgren M Söderström I Del-Favero J Adolfsson R Norrback KF 《PloS one》2011,6(3):e18035
Background
The catechol-O-methyltransferase (COMT) enzyme has a key function in the degradation of catecholamines and a functional polymorphism is val158met. The val/val genotype results in a three to fourfold higher enzymatic activity compared with the met/met genotype, with the val/met genotype exhibiting intermediate activity. Since pain syndromes as well as anxiety and depression are associated to low and high COMT activity respectively and these conditions are all associated with irritable bowel syndrome (IBS) we wanted for the first time to explore the relationship between the polymorphism and IBS.Methodology/Principal Findings
867 subjects (445 women) representative of the general population and 70 consecutively sampled patients with IBS (61 women) were genotyped for the val158met polymorphism and the IBS patients filled out the Hospital-Anxiety-and-Depression-Scale (HADS) questionnaire, and an IBS symptom diary.Results
There was a significantly higher occurrence of the val/val genotype in patients compared with controls (30% vs 20%; Chi2 (1) 3.98; p = 0.046) and a trend toward a lower occurrence of the val/met genotype in IBS patients compared with controls (39% vs 49%; Chi2 (1) 2.89; p = 0.089). Within the IBS patients the val/val carriers exhibited significantly increased bowel frequency (2.6 vs 1.8 stools per day; Chi2 (1) 5.3; p = 0.03) and a smaller proportion of stools with incomplete defecation (41% vs 68%; Chi2 (1) 4.3; p = 0.04) compared with the rest (val/met+met/met carriers). The val/val carriers also showed a trend for a smaller proportion of hard stools (0% vs 15%; Chi2 (1) 3.2; p = 0.08) and a higher frequency of postprandial defecation (26% vs 21%; Chi2 (1) 3.0; p = 0.08).Conclusions/Significance
In this study we found an association between the val/val genotype of the val158met COMT gene and IBS as well as to specific IBS related bowel pattern in IBS patients. 相似文献11.
Wendy Dávila Nieves Basterreche Aurora Arrue María I. Zamalloa Estíbaliz Gordo Ricardo Dávila Miguel A. González-Torres Mercedes Zumárraga 《PloS one》2013,8(4)
Introduction
Certain personality traits and genetic polymorphisms are contributing factors to bipolar disorder and its symptomatology, and in turn, this syndrome influences personality. The aim of the present study is to compare the personality traits of euthymic bipolar patients with healthy controls and to investigate the effect of the catechol-O-methyltransferase (COMT) Val158Met genotype on those traits. We recruited thirty seven bipolar I patients in euthymic state following a manic episode and thirty healthy controls and evaluated their personality by means of the Cloninger’s Temperament and Character Inventory (version TCI-R-140). We assessed the influence of the polymorphism Val158Met in the COMT gene on the personality of these patients. The patients scored higher than controls in harm avoidance (61.3±12.5 vs. 55.3±8.1) and self-transcendence (45.3±12.8 vs. 32.7±8.2) and scored lower than controls in self-directedness (68.8±13.3 vs. 79.3±8.1), cooperativeness (77.1±9.1 vs. 83.9±6.5) and persistence (60.4±15.1 vs. 67.1±8.9). The novelty seeking dimension associates with the Val158Met COMT genotype; patients with the low catabolic activity genotype, Met/Met, show a higher score than those with the high catabolic activity genotype, Val/Val.Conclusions
Suffering from bipolar disorder could have an impact on personality. A greater value in harm avoidance may be a genetic marker for a vulnerability to the development of a psychiatric disorder, but not bipolar disorder particularly, while a low value in persistence may characterize affective disorders or a subgroup of bipolar patients. The association between novelty seeking scores and COMT genotype may be linked with the role dopamine plays in the brain’s reward circuits. 相似文献12.
Ryu Takizawa Mamoru Tochigi Yuki Kawakubo Kohei Marumo Tsukasa Sasaki Masato Fukuda Kiyoto Kasai 《PloS one》2009,4(5)
Background
“Imaging genetics” studies have shown that brain function by neuroimaging is a sensitive intermediate phenotype that bridges the gap between genes and psychiatric conditions. Although the evidence of association between functional val108/158met polymorphism of the catechol-O-methyltransferase gene (COMT) and increasing risk for developing schizophrenia from genetic association studies remains to be elucidated, one of the most topical findings from imaging genetics studies is the association between COMT genotype and prefrontal function in schizophrenia. The next important step in the translational approach is to establish a useful neuroimaging tool in clinical settings that is sensitive to COMT variation, so that the clinician could use the index to predict clinical response such as improvement in cognitive dysfunction by medication. Here, we investigated spatiotemporal characteristics of the association between prefrontal hemodynamic activation and the COMT genotype using a noninvasive neuroimaging technique, near-infrared spectroscopy (NIRS).Methodology/Principal Findings
Study participants included 45 patients with schizophrenia and 60 healthy controls matched for age and gender. Signals that are assumed to reflect regional cerebral blood volume were monitored over prefrontal regions from 52-channel NIRS and compared between two COMT genotype subgroups (Met carriers and Val/Val individuals) matched for age, gender, premorbid IQ, and task performance. The [oxy-Hb] increase in the Met carriers during the verbal fluency task was significantly greater than that in the Val/Val individuals in the frontopolar prefrontal cortex of patients with schizophrenia, although neither medication nor clinical symptoms differed significantly between the two subgroups. These differences were not found to be significant in healthy controls.Conclusions/Significance
These data suggest that the prefrontal NIRS signals can noninvasively detect the impact of COMT variation in patients with schizophrenia. NIRS may be a promising candidate translational approach in psychiatric neuroimaging. 相似文献13.
Schmidt S Naranjo JR Brenneisen C Gundlach J Schultz C Kaube H Hinterberger T Jeanmonod D 《PloS one》2012,7(3):e31138
Objectives
Several recent studies report the presence of a specific EEG pattern named Thalamocortical Dysrhythmia (TCD) in patients with severe chronic neurogenic pain. This is of major interest since so far no neuroscientific indicator of chronic pain could be identified. We investigated whether a TCD-like pattern could be found in patients with moderate chronic back pain, and we compared patients with neuropathic and non-neuropathic pain components. We furthermore assessed the presence of psychopathology and the degree of psychological functioning and examined whether the strength of the TCD-related EEG markers is correlated with psychological symptoms and pain ratings.Design
Controlled clinical trial with age and sex matched healthy controls.Methods
Spontaneous EEG was recorded in 37 back pain patients and 37 healthy controls.Results
We were not able to observe a statistically significant TCD effect in the EEG data of the whole patient group, but a subsample of patients with evidence for root damage showed a trend in this direction. Pain patients showed markedly increased psychopathology. In addition, patients'' ratings of pain intensity within the last 1 to 12 months showed strong correlations with EEG power, while psychopathology was correlated to the peak frequency.Conclusion
Out of several possible interpretations the most likely conclusion is that only patients with severe pain as well as root lesions with consecutive thalamic deafferentation develop the typical TCD pattern. Our primary method of defining ‘neuropathic pain’ could not reliably determine if such a deafferentation was present. Nevertheless the analysis of a specific subsample as well as correlations between pain ratings, psychopathology and EEG power and peak frequency give some support to the TCD concept.Trial Registration
ClinicalTrials.gov NCT00744575相似文献14.
Li-Min Wu Mei-Hong Hu Xian-Hong Tong Hui Han Ni Shen Ren-Tao Jin Wei Wang Gui-Xiang Zhou Guo-Ping He Yu-Sheng Liu 《PloS one》2012,7(12)
Background
Brain-derived neurotropic factor (BDNF) was originally described in the nervous system but has been shown to be expressed in ovary tissues recently, acting as a paracrine/autocrine regulator required for developments of follicles and oocytes. Although it is generally accepted that chronic stress impairs female reproduction and decreases the expression of BDNF in limbic structures of central nervous system, which contributes to mood disorder. However, it is not known whether chronic stress affects oocytes developments, nor whether it affects expression of BDNF in ovary.Methods
Mice were randomly assigned into control group, stressed group, BDNF-treated group and BDNF-treated stressed group. The chronic unpredictable mild stress model was used to produce psychosocial stress in mice, and the model was verified by open field test and hypothalamic-pituitary-adrenal (HPA) axis activity. The methods of immunohistochemistry and western blotting were used to detect BDNF protein level and distribution. The number of retrieved oocytes, oocyte maturation, embryo cleavage and the rates of blastocyst formation after parthenogenetic activation were evaluated.Results
Chronic unpredictable stress decreased the BDNF expression in antral follicles, but didn’t affect the BDNF expression in primordial, primary and secondary follicles. Chronic unpredictable stress also decreased the number of retrieved oocytes and the rate of blastocyst formation, which was rescued by exogenous BDNF treatment.Conclusion
BDNF in mouse ovaries may be related to the decreased number of retrieved oocytes and impaired oocytes developmental potential induced by chronic unpredictable stress. 相似文献15.
V Pieramico R Esposito F Sensi F Cilli D Mantini PA Mattei V Frazzini D Ciavardelli V Gatta A Ferretti GL Romani SL Sensi 《PloS one》2012,7(8):e43901
Background
Aging is a major co-risk factor in many neurodegenerative diseases. Cognitive enrichment positively affects the structural plasticity of the aging brain. In this study, we evaluated effects of a set of structured multimodal activities (Combination Training; CT) on cognitive performances, functional connectivity, and cortical thickness of a group of healthy elderly individuals. CT lasted six months.Methodology
Neuropsychological and occupational performances were evaluated before and at the end of the training period. fMRI was used to assess effects of training on resting state network (RSN) functional connectivity using Independent Component Analysis (ICA). Effects on cortical thickness were also studied. Finally, we evaluated whether specific dopamine-related genes can affect the response to training.Principal Findings
Results of the study indicate that CT improves cognitive/occupational performances and reorganizes functional connectivity. Intriguingly, individuals responding to CT showed specific dopamine-related genotypes. Indeed, analysis of dopamine-related genes revealed that carriers of DRD3 ser9gly and COMT Val158Met polymorphisms had the greatest benefits from exposure to CT.Conclusions and Significance
Overall, our findings support the idea that exposure to a set of structured multimodal activities can be an effective strategy to counteract aging-related cognitive decline and also indicate that significant capability of functional and structural changes are maintained in the elderly. 相似文献16.
Background
Intense abdominal pain is the dominant feature of chronic pancreatitis. During the disease changes in central pain processing, e.g. central sensitization manifest as spreading hyperalgesia, can result from ongoing nociceptive input. The aim of the present study is to evaluate the effect of pregabalin on pain processing in chronic pancreatitis as assessed by quantitative sensory testing (QST).Methods
This randomized, double-blind, placebo-controlled trial evaluated effects of pregabalin on pain processing. QST was used to quantify pain processing by measuring thresholds to painful electrical and pressure stimulation in six body dermatomes. Descending endogenous pain modulation was quantified using the conditioned pain modulation (CPM) paradigm to elicit a DNIC (diffuse noxious inhibitory controls) response. The main effect parameter was the change in the sum of all body pain threshold values after three weeks of study treatment versus baseline values between both treatment groups.Results
64 patients were analyzed. No differences in change in sum of pain thresholds were present for pregabalin vs. placebo after three weeks of treatment. For individual dermatomes, change vs. baseline pain thresholds was significantly greater in pregabalin vs. placebo patients for electric pain detection threshold in C5 (P = 0.005), electric pain tolerance threshold in C5 (P = 0.04) and L1 (P = 0.05), and pressure pain tolerance threshold in T4 (P = 0.004). No differences were observed between pregabalin and placebo regarding conditioned pain modulation.Conclusion
Our study provides first evidence that pregabalin has moderate inhibitory effects on central sensitization manifest as spreading hyperalgesia in chronic pancreatitis patients. These findings suggest that QST can be of clinical use for monitoring pain treatments in the context of chronic pain.Trial Registration
ClinicalTrials.gov NCT00755573相似文献17.
Yen Ying Lim Victor L. Villemagne Simon M. Laws David Ames Robert H. Pietrzak Kathryn A. Ellis Karra Harrington Pierrick Bourgeat Ashley I. Bush Ralph N. Martins Colin L. Masters Christopher C. Rowe Paul Maruff for the AIBL Research Group 《PloS one》2014,9(1)
Objective
Cross-sectional genetic association studies have reported equivocal results on the relationship between the brain-derived neurotrophic factor (BDNF) Val66Met and risk of Alzheimer’s disease (AD). As AD is a neurodegenerative disease, genetic influences may become clearer from prospective study. We aimed to determine whether BDNF Val66Met polymorphism influences changes in memory performance, hippocampal volume, and Aβ accumulation in adults with amnestic mild cognitive impairment (aMCI) and high Aβ.Methods
Thirty-four adults with aMCI were recruited from the Australian, Imaging, Biomarkers and Lifestyle (AIBL) Study. Participants underwent PiB-PET and structural MRI neuroimaging, neuropsychological assessments and BDNF genotyping at baseline, 18 month, and 36 month assessments.Results
In individuals with aMCI and high Aβ, Met carriers showed significant and large decline in episodic memory (d = 0.90, p = .020) and hippocampal volume (d = 0.98, p = .035). BDNF Val66Met was unrelated to the rate of Aβ accumulation (d = −0.35, p = .401).Conclusions
Although preliminary due to the small sample size, results of this study suggest that high Aβ levels and Met carriage may be useful prognostic markers of accelerated decline in episodic memory, and reductions in hippocampal volume in individuals in the prodromal or MCI stage of AD. 相似文献18.
Ronkainen PH Pöllänen E Törmäkangas T Tiainen K Koskenvuo M Kaprio J Rantanen T Sipilä S Kovanen V 《PloS one》2008,3(3):e1819
Background
Muscle strength declines on average by one percent annually from midlife on. In postmenopausal women this decrement coincides with a rapid decline in estrogen production. The genetics underlying the effects of estrogen on skeletal muscle remains unclear. In the present study, we examined whether polymorphisms within COMT and ESR1 are associated with muscle properties and assessed their interaction and their combined effects with physical activity.Methodology/Principal Findings
A cross-sectional data analysis was conducted with 434 63-76-year-old women from the population-based Finnish Twin Study on Aging. Body anthropometry, muscle cross-sectional area (mCSA), isometric hand grip and knee extension strengths, and leg extension power were measured. COMT Val158Met and ESR1 PvuII genotypes were determined by the RFLP method. mCSA differed by COMT genotypes (p = 0.014) being significantly larger in LL than HL individuals in unadjusted (p = 0.001) and age- and height-adjusted model (p = 0.004). When physical activity and age were entered into GEE model, COMT genotype had a significant main effect (p = 0.038) on mCSA. Furthermore, sedentary individuals with the HH genotype had lower muscle mass, strength and power, but they also appeared to benefit the most from physical activity. No association of ESR1 PvuII polymorphism with any of the muscle outcomes was observed.Conclusions/Significance
The present study suggests that the COMT polymorphism, affecting the activity of the enzyme, is associated with muscle mass. Furthermore, sedentary individuals with potential high enzyme activity were the weakest group, but they may potentially benefit the most from physical activity. This observation elucidates the importance of both environmental and genetic factors in muscle properties. 相似文献19.
Stefan A. W. Bouwense S?ren S. Olesen Asbj?rn M. Drewes Jens B. Fr?kj?r Harry van Goor Oliver H. G. Wilder-Smith 《PloS one》2013,8(2)
Background
The most dominant feature in chronic pancreatitis is intense abdominal pain. Changes in spinal and/or supraspinal central nervous system pain processing due to visceral nociceptive input play an important role in this pain. How altered pain processing is related to disease stage still needs study.Methodology/Principal Findings
Sixty chronic pancreatitis patients were compared to 15 healthy controls. Two subgroups of pancreatitis patients were defined based on the M-ANNHEIM severity index of chronic pancreatitis; i.e. moderate and severe. Pain detection and tolerance thresholds for pressure and electric stimuli were measured in six selected dermatomes (C5, T4, T10, L1, L4 and T10BACK). In addition, the conditioned pain modulation response to cold pressor task was determined. These measures were compared between the healthy controls and chronic pancreatitis patients. Severe pancreatitis patients showed lower pain thresholds than moderate pancreatitis patients or healthy volunteers. Healthy controls showed a significantly larger conditioned pain modulation response compared to all chronic pancreatitis patients taken together.Conclusions/Significance
The present study confirms that chronic pancreatitis patients show signs of altered central processing of nociception compared to healthy controls. The study further suggests that these changes, i.e. central sensitization, may be influenced by disease stage. These findings underline the need to take altered central pain processing into account when managing the pain of chronic pancreatitis. 相似文献20.
Rakib U. Rayhan Benson W. Stevens Christian R. Timbol Oluwatoyin Adewuyi Brian Walitt John W. VanMeter James N. Baraniuk 《PloS one》2013,8(3)