We previously demonstrated that serotonin (5-HT) and 5-HT2A receptor (5-HT2AR) levels in platelets were up- or down-regulated after myocardial infarction (MI) associated with depression. In this study, we further evaluated the effects of pretreatment with ginseng fruit saponins (GFS) on the expression of 5-HT and 5-HT2AR in MI with or without depression. Eighty Sprague-Dawley (SD) rats were treated with saline and GFS (n=40 per group). The animals were then randomly divided into four subgroups: sham, MI, depression, and MI + depression (n=10 per subgroup). Protein levels of 5-HT and 5-HT2AR in the serum, platelets and brain tissues were determined with ELISA. The results demonstrated that serum 5-HT levels was significantly increased by GFS pretreatment in all subgroups (except the sham subgroup) when compared with saline-treated counterparts (p<0.01). In platelets, GFS pretreatment significantly increased 5-HT levels in all subgroups when compared with their respective saline-treated counterparts (p<0.01). Brain 5-HT levels also declined with GFS pretreatment in the MI-only and depression-only subgroups (p<0.05 vs. saline pretreatment). With respect to 5-HT2AR levels, platelet 5-HT2AR was decreased in GFS pretreated MI, depression and MI + depression subgroups (p<0.01 vs. saline pretreatment). Similarly, brain 5-HT2AR levels decreased in all four subgroups pretreated with GFS (p<0.01 vs. saline pretreatment). We conclude that GFS plays a clear role in modulating 5-HT and 5-HT2AR expressions after MI and depression. Although the effects of GFS on brain 5-HT remain to be elucidated, its therapeutic potential for comorbidities of acute cardiovascular events and depression appears to hold much promise.
Post-stroke depression (PSD) is a common psychiatric complication of stroke that is associated with a poor outcome in stroke patients. Our aim was to assess the association between the serum magnesium levels and the presence of PSD in Chinese patients. Two hundred nine stroke patients were included in the study. Depressive symptoms were measured by the 17-Hamilton Rating Scale for Depression at 3 months after stroke. Based on the depressive symptoms, diagnoses of depression were made in line with the DSM-IV criteria for PSD. Serum magnesium levels were evaluated using the dimethyl aniline blue colorimetric method at admission. Multivariate analyses were conducted using logistic regression models. Further, 120 normal subjects were recruited, and their serum magnesium levels were also measured as control. At 3 months, fifty-nine patients (28.2%) were diagnosed as PSD. The serum magnesium levels were significantly lower in both PSD patients and non-PSD patients than in normal subjects (p < 0.001). Indeed, patients with PSD showed lower serum magnesium levels (p < 0.001) than did non-PSD patients at admission. In the multivariate analyses, after adjusting for potential variables, we found that an increased risk of PSD was associated with serum magnesium levels ≤ 0.84mmol/L (OR 2.614, 95% CI 1.178-5.798, p=0.018). Low serum magnesium levels at admission were found to be associated with the presence of PSD at 3 months after stroke.
Slow wave sleep abnormality has been reported in neuromyelitis optica spectrum disorder (NMOSD), but mechanism for such abnormality is unknown. To determine the structural defects in the brain that account for the decrease of slow wave sleep in NMOSD patients. Thirty-three NMOSD patients and 18 matched healthy controls (HC) were enrolled. Polysomnography was used to monitor slow wave sleep and three-dimensional T1-weighted MRIs were obtained to assess the alterations of grey matter volume. The percentage of deep slow wave sleep decreased in 93% NMOSD patients. Compared to HC, a reduction of grey matter volume was found in the bilateral thalamus of patients with a lower percentage of slow wave sleep (FWE corrected at cluster-level, p < 0.05, cluster size > 400 voxels). Furthermore, the right thalamic fraction was positively correlated with the decrease in the percentage of slow wave sleep in NMOSD patients (p < 0.05, FDR corrected, cluster size > 200 voxels). Our study identified that thalamic atrophy is associated with the decrease of slow wave sleep in NMOSD patients. Further studies should evaluate whether neurotransmitters or hormones which stem from thalamus are involved in the decrease of slow wave sleep.
Muscle power is a strong predictor of functional status in the elderly population and is required to perform different daily activities. To compare the effects of different weekly training frequencies on muscle power and muscle quality induced by concurrent training (resistance + aerobic) in previously trained elderly men. Twenty-four trained elderly men (65 ± 4 years), previously engaged in a regular concurrent training program, three times per week, for the previous five months, were randomly allocated to concurrent training programs in which training was performed either twice a week (2·week-1, n = 12) or three times per week (3·week-1, n = 12). The groups trained with an identical exercise intensity and volume per session for 10 weeks. Before and after the exercise training, we examined muscle power, as estimated by countermovement jump height; knee extensor isokinetic peak torque at 60 and 180o.s-1; and muscle quality, a quotient between the one-repetition maximum of the knee extensors and the sum of quadriceps femoris muscle thickness determined by ultrasonography. Additionally, as secondary outcomes, blood pressure and reactive hyperemia were evaluated. Two-way ANOVA with repeated measures were used and statistical significance was set at α = 0.05. Muscular power (2·week-1: 7%, and 3·week-1: 10%) and muscle quality (2·week-1: 15%, and 3·week-1: 8%) improved with the concurrent exercise training (p < 0.001) but with no differences between groups. The isokinetic peak torque at 60 (2·week-1: 4%, and 3·week-1: 2%) and 180o.s-1 (2·week-1: 7%, and 3·week-1: 1%) increased in both groups (p = 0.036 and p=0.014, respectively). There were no changes in blood pressure or reactive hyperemia with the concurrent training. Concurrent training performed twice a week promotes similar adaptations in muscular power and muscle quality when compared with the same program performed three times per week in previously trained elderly men.
MicroRNA-181 (miR-181) is highly expressed in the brain, and downregulated in miRNA expression profiles of acute ischemic stroke patients. However, the roles of miR-181c in stroke are not known. The clinical relevance of miR-181c in acute stroke patients was evaluated by real-time PCR and correlation analyses. Proliferation and apoptosis of BV2 microglial cells and Neuro-2a cells cultured separately or together under oxidative stress or inflammation were assessed with the Cell Counting Kit-8 and by flow cytometry, respectively. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in C57/BL6 mice, and cerebral infarct volume, microglia activation, and expression of pro-apoptotic factors were evaluated by 2,3,5-triphenyl-2H-tetrazolium chloride staining, immunocytochemistry, and western blotting, respectively. Plasma levels of miR-181c were decreased in stroke patients relative to healthy individuals, and were positively correlated with neutrophil number and blood platelet count and negatively correlated with lymphocyte number. Lipopolysaccharide (LPS)/hydrogen peroxide (H2O2) treatment inhibited BV2 microglia proliferation without inducing apoptosis, while miR-181c reduced proliferation but increased the apoptosis of these cells with or without LPS/H2O2 treatment. LPS/H2O2 induced apoptosis in Neuro-2a cells co-cultured with BV2 cells, an effect that was potentiated by miR-181c. In the MCAO model, miR-181c agomir modestly increased infarct volume, markedly decreased microglia activation and B cell lymphoma-2 expression, and increased the levels of pro-apoptotic proteins in the ischemic brain. Our data indicate that miR-181c contributes to brain injury in acute ischemic stroke by promoting apoptosis of microglia and neurons via modulation of pro- and anti-apoptotic proteins.
The study was designed to investigate the clinical application and significance of the bulbocavernosus reflex (BCR) test for diagnosing diabetic neurogenic bladder (DNB) in female subjects. In this study, 68 female patients with DNB and 40 female normal controls were subjected to a nerve conduction study (NCS) of all four limbs and the BCR test. The data were analyzed and compared, and the corresponding diagnostic sensitivities were discussed. Mean BCR latency for female DNB patients was significantly prolonged, compared to that of the control group, suggesting pudendal nerve injuries in female DNB patients. Moreover, DNB patients were categorized according to the diabetes course. Compared to that of Group A (diabetes course < 5 y), the mean BCR latency was significantly prolonged in Group B (diabetes course between 5 and 10 y) and then further prolonged in Group C (diabetes course > 10 y), which were all longer than the control group. Furthermore, compared with that of the controls, the mean BCR latency was prolonged in DNB patients with or without NCS abnormalities in limbs. Nevertheless, no significant difference was observed in BCR latency between DNB patients with and without NCS abnormalities. Significantly increasing trends were also observed in the NCS and BCR abnormality rates along with increased diabetes course. Most importantly, compared with the NCS of limbs, the BCR test was more sensitive in diagnosing DNB in the female subjects. Overall, our findings suggest that the BCR test would help to assess the pudendal nerve injury in female DNB patients, which might be a potential diagnostic tool in the clinic.
The effect of weight loss from long-term, mild-calorie diets (MCD) on plasma metabolites is unknown. This study was to examine whether MCD-induced weight reduction caused changes in the extended plasma metabolites. Overweight and obese subjects aged 40-59 years consumed a MCD (approximately 100 kcal/day deficit, n=47) or a weight-maintenance diet (control, n=47) in a randomized, controlled design with a three-year clinical intervention period and plasma samples were analyzed by using UPLC-LTQ-Orbitrap mass spectrometry. The three-year MCD intervention resulted in weight loss (-8.87%) and significant decreases in HOMA-IR and TG. The three-year follow-up of the MCD group showed reductions in the following 13 metabolites: L-leucine; L-phenylalanine; 9 lysoPCs; PC (18:0/20:4); and SM (d18:0/16:1). The three-year MCD group follow-up identified increases in palmitic amide, oleamide, and PC (18:2/18:2). Considering the age-related alterations in the identified metabolites, the MCD group showed a greater decrease in L-leucine, L-phenylalanine, and SM (d18:0/16:1) compared with those of the control group. Overall, the change (Δ) in BMI positively correlated with the ΔTG, ΔHOMA-IR, ΔL-leucine, and ΔSM (d18:0/16:1). The ΔHOMA-IR positively correlated with ΔTG, ΔL-leucine, ΔL-phenylalanine, and ΔSM (d18:0/16:1). The weight loss resulting from three-year mild-caloric restriction lessens the age-related increase in SM and reduces L-leucine and L-phenylalanine in overweight and obese subjects. These changes were coupled with improved insulin resistance (ClinicalTrials.gov: NCT02081898).
Subclinical hyperthyroidism is known to be associated with the risk of fractures in elderly people. However, there are few studies assessing whether low normal thyroid-stimulating hormone (TSH) levels affect bone density and geometry. Here, we aimed to assess the influence of the TSH level on bone mineral density (BMD) and geometry in elderly euthyroid subjects. This was a cross-sectional cohort study. A total of 343 men and 674 women with euthyroidism were included and analyzed separately. The subjects were divided into tertiles based on the serum TSH level. The BMD and geometry were measured using dual-energy X-ray absorptiometry and a hip structural analysis program. Multiple regression analysis was used to compute the odds ratios of osteoporosis in the lower TSH tertile group and the association between geometry parameters and the TSH level. We found that the femoral neck and total hip BMDs were lower in the lower TSH tertile group. In women, the cross-sectional area and cortical thickness of the femur were negatively associated with the TSH level in all three regions (the narrow neck, intertrochanter, and femoral shaft); however, in men, these geometry parameters were significantly associated with the TSH level only in the intertrochanter region. The buckling ratio, a bone geometry parameter representing cortical instability, was significantly higher in the lower TSH tertile group in all three regions in women, but not in men. Our results indicated that lower TSH levels in the euthyroid range are related to lower BMD and weaker femoral structure in elderly women.
Flavonoids are known to trigger the intrinsic genetic adaptive programs to hypoxic or oxidative stress via estrogen receptor engagement or upstream kinase activation. To reveal specific structural requirements for direct stabilization of the transcription factors responsible for triggering the antihypoxic and antioxidant programs, we studied flavones, isoflavones and catechols including dihydroxybenzoate, didox, levodopa, and nordihydroguaiaretic acid (NDGA), using novel luciferase-based reporters specific for the first step in HIF1 or Nrf2 protein stabilization. Distinct structural requirements for either transcription factor stabilization have been found: as expected, these requirements for activation of HIF ODD-luc reporter correlate with in silico binding to HIF prolyl hydroxylase. By contrast, stabilization of Nrf2 requires the presence of 3,4-dihydroxy- (catechol) groups. Thus, only some but not all flavonoids are direct activators of the hypoxic and antioxidant genetic programs. NDGA from the Creosote bush resembles the best flavonoids in their ability to directly stabilize HIF1 and Nrf2 and is superior with respect to LOX inhibition thus favoring this compound over others. Given much higher bioavailability and stability of NDGA than any flavonoid, NDGA has been tested in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-animal model of Parkinson’s Disease and demonstrated neuroprotective effects.
Vision, hearing, olfaction, and cognitive function are essential components of healthy and successful aging. Multiple studies demonstrate relationship between these conditions with cognitive function. The present article focuses on hearing loss, visual impairment, olfactory loss, and dual sensory impairments in relation to cognitive declination and neurodegenerative disorders. Sensorineural organ impairment is a predictive factor for mild cognitive impairment and neurodegenerative disorders in the elderly. We recommend early detection of sensorineural dysfunction by history, physical examination, and screening tests. Assisted device and early cognitive rehabilitation may be beneficial. Future research is warranted in order to explore advanced treatment options and method to slow progression for cognitive declination and sensorineural organ impairment.