Proteomic and metabolomic profiling reveals time-dependent changes in hippocampal metabolism upon paroxetine treatment and biomarker candidates

Most of the commonly used antidepressants block monoamine reuptake transporters to enhance serotonergic or noradrenergic neurotransmission. Effects besides or downstream of monoamine reuptake inhibition are poorly understood and yet presumably important for the drugs' mode of action. In the present study we aimed at identifying hippocampal cellular pathway alterations in DBA/2 mice using paroxetine as a representative Selective Serotonin Reuptake Inhibitor (SSRI). Furthermore we identified biomarker candidates for the assessment of antidepressant treatment effects in plasma. Hippocampal protein levels were compared between chronic paroxetine- and vehicle-treated animals using in vivo¹⁵N metabolic labeling combined with mass spectrometry. We also studied the time course of metabolite level changes in hippocampus and plasma using a targeted polar metabolomics profiling platform. In silico pathway analyses revealed profound alterations related to hippocampal energy metabolism. Glycolytic metabolite levels acutely increased while Krebs cycle metabolite levels decreased upon chronic treatment. Changes in energy metabolism were influenced by altered glycogen metabolism rather than by altered glycolytic or Krebs cycle enzyme levels. Increased energy levels were reflected by an increased ATP/ADP ratio and by increased ratios of high-to-low energy purines and pyrimidines. In the course of our analyses we also identified myo-inositol as a biomarker candidate for the assessment of antidepressant treatment effects in the periphery. This study defines the cellular response to paroxetine treatment at the proteome and metabolome levels in the hippocampus of DBA/2 mice and suggests novel SSRI modes of action that warrant consideration in antidepressant development efforts.     

Psychotherapy supervision conducted via videoconferencing: A qualitative study of users' experiences

Forty-three patients who had been treated in hospital for major depression were studied 1 to 2 years after discharge. Patients retrospectively ranked physical exercise as the most important element in the comprehensive treatment programme. Most subjects continued with regular exercise after discharge, and most of these exercised aerobically at least 2 h a week. Exercisers tended to have lower depression scores at follow-up examination than nonexercisers.     

Aerobic training in persons who have recovered from juvenile dermatomyositis

A recent study has shown that 36 persons who had recovered from juvenile dermatomyositis (JDM) have on average an 18% decrease in maximal oxygen uptake. The objective of this study was to investigate the effect of a 12-week aerobic training program in this group, and assess whether aerobic training can normalize aerobic capacity to the expected level for age and gender.The patients participating in the study, one male and nine females (16–42 years of age), were in remission from JDM, defined as no clinical or biochemical evidence of disease activity and no medical treatment for 1 year. The patients had a median disease duration of 3.4 years (1.4–10.3), a median treatment duration of 2.4 years (0.4–9.3) and a median duration of remission of 7.0 years (1.2–30.0).Patients trained at home on a cycle ergometer for 12 weeks at a heart rate interval corresponding to 65% of their maximal oxygen uptake (VO_2max)_. VO_2max and maximal workload (W_max) were determined before and after the 12-week training period through an incremental cycling test to exhaustion. The patients served as their own controls.Eight patients with JDM in remission completed the 12-week exercise program; one patient completed 9 weeks out of the 12-week program and one dropped out of the study. Training increased VO_2max and W_max by 26% and 30% (P < 0.001). Creatine kinase (CK) levels were normal pre-training and did not change with training, reflecting no muscle damage. We also found that at a given workload, heart rate was lowered significantly after the 12-week training period, indicating an improvement in cardiovascular fitness.This study shows that 12 weeks of moderate-intensity aerobic training is an effective and safe method to increase oxidative capacity and fitness in persons who have recovered from JDM. The results indicate that the low oxidative capacity in JDM patients in remission is reversible and can be improved. Thus, we recommend frequent aerobic training to be incorporated into supervised physiotherapy sessions in the treatment of JDM patients in remission.     

Effect of regular exercise on blood pressure in normotensive pregnant women. A randomized controlled trial

Objective: To evaluate the effect of regular exercise on maternal arterial blood pressure (BP) at rest and during uphill walking, in healthy former inactive pregnant women. Methods: A single-blind, single-center, randomized controlled trial including 61 out of 105 healthy, inactive nulliparous pregnant women, initially enrolled in a controlled trial studying the effect of 12 weeks of aerobic exercise (60 min 2/week) on maternal weight gain. Primary outcome was the mean adjusted difference in change in resting systolic and diastolic BP from baseline to after intervention. Secondary outcome was the mean adjusted difference in change in systolic BP during uphill treadmill walking at critical power. Measurements were performed prior to the intervention (gestation week 17.6 ± 4.2) and after the intervention (gestation week 36.5 ± 0.9). Results: At baseline, resting systolic and diastolic BP was 115/66 ± 12/7 and 115/67 ± 10/9 mmHg in the exercise (n = 35) and control group (n = 26), respectively. After the intervention, resting systolic BP was 112 ± 8 mmHg in the exercise group and 119 ± 14 mmHg in the control group, giving a between-group difference of 7.5 mmHg (95% CI 1.5 to 12.6, p = 0.013). Diastolic BP was 71 ± 9 and 76 ± 8 mmHg, with a between-group difference of 3.9 mmHg (95% CI ?0.07 to 7.8, p = 0.054). During uphill treadmill walking at critical power, the between-group difference in systolic and diastolic BP was 5.9 mmHg (95% CI ?4.4 to 16.1, p = 0.254) and 5.5 mmHg (95% CI –0.2 to 11.1, p = 0.059), respectively. Conclusions: Aerobic exercise reduced resting systolic BP in healthy former inactive pregnant women.     

有氧运动通过上调Dhcr24改善H2O2诱导的心肌细胞凋亡

目的 研究Dhcr24在有氧运动改善心肌梗死(myocardial infarction,MI)后心肌细胞功能中的潜在作用及分子机制。方法 通过H2O2建立心肌细胞(H9C2)凋亡模型,并通过AMPK激动剂AICAR来模拟心肌细胞的运动效果。通过流式细胞术和TUNEL检测心肌细胞凋亡水平;通过Western blot检测心肌细胞中凋亡相关蛋白Bcl-2、Bax和Dhcr24的表达水平;通过RT-qPCR检测细胞中Dhcr24 mRNA的水平。结果 与对照组相比,H2O2诱导的心肌细胞凋亡率增加、TUNEL阳性粒子数升高、抗凋亡蛋白Bcl-2水平降低、促凋亡蛋白Bax水平升高、Dhcr24水平降低。与H2O2诱导的心肌细胞相比,AMPK激活剂AICAR处理后,心肌细胞凋亡率、TUNEL阳性粒子数降低、Dhcr24水平升高。在H2O2和AICAR共同处理的心肌细胞中敲低Dhcr24,降低的细胞凋亡率、TUNEL阳性粒子数得到逆转。结论 有氧运动对H2O2诱导的心肌细胞凋亡具有明显保护作用,可能与其上调Dhcr24表达有关。     

Maximal Oxygen Consumption and Bone Mineral Density in a Group of Young Lebanese Adults

The aim of this study was to explore the relationship between maximal oxygen consumption (VO₂ max) and bone mineral density (BMD) in a group of young Lebanese adults. Twenty women and 37 men whose ages range from 18 to 32 yr participated in this study. Informed written consent was obtained from the participants. Body weight and height were measured, and body mass index was calculated. VO₂ max was determined by direct measurement while exercising on a bicycle ergometer (Siemens-Elema RE 820; Rodby Elektronik AB, Enhorna, Sweden). Whole body bone mineral content (WB BMC), whole body bone mineral density (WB BMD), lumbar spine BMD (L1–L4 BMD), total hip BMD (TH BMD), and femoral neck BMD (FN BMD) were measured by dual-energy X-ray absorptiometry. In women, VO₂ max (expressed as L/mn) was positively correlated to WB BMC (r = 0.82; p < 0.001), WB BMD (r = 0.80; p < 0.001), L1–L4 BMD (r = 0.73; p < 0.001), TH BMD (r = 0.80; p < 0.001), and FN BMD (r = 0.85; p < 0.001). In men, VO₂ max (expressed as L/mn) was positively correlated to WB BMC (r = 0.57; p < 0.001), WB BMD (r = 0.53; p < 0.001), L1–L4 BMD (r = 0.50; p < 0.001), TH BMD (r = 0.38; p < 0.01), and FN BMD (r = 0.30; p < 0.05). In both sexes, the positive associations between VO₂ max and bone variables (BMC and BMD) remained significant after adjustment for age (p < 0.001). This study suggests that VO₂ max (L/mn) is a positive determinant of BMC and BMD in young adults. Aerobic power seems to be a determinant of BMC and BMD in young adults.     

Effects of aerobic training and resistance training in reducing cardiovascular disease risk for patients with prediabetes: A multi-center randomized controlled trial

AimsAerobic training (AT) and resistance training (RT) can reduce blood glucose and type 2 diabetes risk, and increase muscle mass for prediabetes patients. However, the impact of long-term AT and RT on cardiovascular disease (CVD) risk remains unclear. The purpose of this study was to investigate the impact of AT and RT on CVD risk reduction in prediabetes patients.Materials and methods248 prediabetes patients were enrolled in this multi-center randomized controlled trial (RCT). Patients were randomly divided into 3 groups: RT (n = 82), aerobic training (AT (n = 83)), and control group (n = 83). Participants in RT and AT groups had moderate RT or AT 3 times a week (150 min/week) under supervision in 3 research centers for 24 months. Primary outcome was CVD risk measured by Framingham Risk Score (FRS) and The Chinese 10-year ischemic cardiovascular disease (ICVD) risk assessment tool. Secondary outcomes included in HOMA2-IR, HbA1c, blood pressure and serum lipid profile.ResultsBoth RT and AT groups experienced a significant reduction in HOMA2-IR, HbA1c, LDL-C, TC, SBP, and DBP at the end of 12 and 24 months. Compared to the control group, Both RT and AT groups had significant reduction of the Chinese 10-year ICVD risk (P < 0.05), but FRS CVD risk declined significantly only in the AT group (all P < 0.05). Although FRS CVD risk decreased more in the RT group than in the control group, the difference was not statistically significant. After adjusting for age, gender, statin use, BMI, and WHR, in COX’s proportional hazard model, RT (HR = 0.419, P = 0.037) and AT (HR = 0.310, P = 0.026) were protective factors for CVD risk in prediabetes patients. 24-month RT and AT decreased respectively 58.1% and 69.0% of CVD risk (10-year ICVD risk assessment) in prediabetes patients.ConclusionsThis study demonstrated that 24-month moderate AT reduces the Chinese 10-year ICVD risk and FRS CVD risk in prediabetes patients. RT groups had significant reduction of CVD risk (10-year ICVD risk assessment) in prediabetes patients.Trial registrationClinical trial registration number: NCT 02561377.Date of registration24/09/2015.     

中等强度有氧运动对去卵巢大鼠心肌纤维化的影响

目的 观察中等强度有氧运动对去卵巢大鼠心肌纤维化以及心功能的影响,并探讨其可能作用机制。 方法 采用随机数字表法将30只雌性SD大鼠分为假手术组（简称对照组）、去卵巢组及去卵巢运动组（简称运动组）。对照组大鼠仅切除双侧卵巢附近脂肪组织,去卵巢组及运动组大鼠均行双侧卵巢切除术。制模后对照组及去卵巢组大鼠置于笼内安静饲养,运动组大鼠则进行10周中等强度跑台运动（跑台速度为16~24 m/min）。于末次运动结束后48 h采用超声心动术检测各组大鼠心脏结构及功能,采用Masson染色进行心肌组织病理学观察并获取心肌胶原容积分数（CVF）,采用比色法检测心肌I型胶原（Col-I）和III型胶原（Col-III）含量,采用Western blot法检测心肌基质金属蛋白酶-2（MMP-2）和组织金属蛋白酶抑制物-2（TIMP-2）蛋白表达量。 结果 与对照组比较,去卵巢组大鼠心肌CVF、Col-I和Col-III含量均明显升高（P<0.05）,左心室射血分数（LVEF）、64 kDa MMP-2和TIMP-2蛋白表达量以及64 kDa MMP-2/TIMP-2比值均明显降低（P<0.05）;与去卵巢组比较,运动组大鼠心肌CVF、Col-I和Col-III含量均明显降低（P<0.05）,LVEF、64 kDa MMP-2和TIMP-2蛋白表达量以及64 kDa MMP-2/TIMP-2比值均明显升高（P<0.05）;3组大鼠72 kDa MMP-2蛋白表达量组间差异均无统计学意义（P>0.05）。 结论 中等强度有氧运动能改善去卵巢大鼠心肌纤维化并提高心功能,其治疗机制可能与维持MMP-2/TIMP-2系统稳态平衡有关。     

The effect of 4-week aerobic exercise program on postural balance in postmenopausal women with osteoporosis

The aim of this study is to evaluate the effect of submaximal aerobic exercise program on postural balance in postmenopausal women with osteoporosis. Twenty-five postmenopausal women without osteoporosis and 28 postmenopausal women with osteoporosis enrolled in this study. Balance ability of all subjects was measured by timed up and go test (TUG), four square step test (FSS), Berg balance scale (BBS) and Kinesthetic ability trainer 3000. After completion of initial measurements of balance, postmenopausal women with osteoporosis attended the submaximal aerobic exercise program on treadmill. At the end of the exercise program, balance tests were repeated. Balance tests of postmenopausal women without osteoporosis were repeated approximately 4-weeks after the initial measurement. There was statistically significant improvement in all balance scores in the postmenopausal women with osteoporosis after exercise training whereas there were no statistically significant differences in the scores of postmenopausal women without osteoporosis who did not exercise. This study showed that a 4-week submaximal aerobic exercise program provided significant improvements in static and dynamic balances in postmenopausal osteoporotic women.     

Effects of aerobic or resistance exercise training on cardiovascular autonomic function of subjects with type 2 diabetes: A pilot study

Background and aims

Both aerobic (AER) and resistance (RES) training improve metabolic control in patients with type 2 diabetes (T2DM). However, information on the effects of these training modalities on cardiovascular autonomic control is limited. Our aim was to compare the effects of AER and RES training on cardiovascular autonomic function in these subjects.