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Study objectivesTo investigate the extent to which sleep quality associated with plasma Aβ levels in amnestic mild cognitive impairment (aMCI) elderly.MethodsA total of 172 cognitively normal (NC) elderly and 133 aMCI elderly were included in this study. For the evaluation of sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. Levels of plasma Aβ were determined by the sandwich enzyme-linked immunosorbent assay technique. Multivariable linear regression analysis was applied to evaluate associations between sleep quality and plasma Aβ levels after adjusting potential confounders.ResultsCompared to NC subjects, participants with aMCI had a higher global PSQI score (8.72 ± 3.87 vs. 7.10 ± 3.07, p < 0.001). The global PSQI score was positively associated with plasma Aβ42 level in the aMCI group (β = 0.063, 95% CI 0.001–0.125, and p = 0.049) but not in the NC group (p > 0.05). Additionally, a higher global PSQI score was associated with a higher plasma Aβ42/Aβ40 ratio in both NC (β = 0.010, 95% CI 0.003–0.016, and p = 0.003) and aMCI groups (β = 0.012, 95% CI 0.005–0.018, and p < 0.001). The association between global PSQI score and plasma Aβ42/Aβ40 ratio was stronger in individuals with aMCI relative to the NC subjects (β = 0.076 vs. 0.030, p for interaction = 0.023).ConclusionPoor sleep quality was associated with plasma Aβ42 and Aβ42/Aβ40 ratio, with a stronger effect among individuals with aMCI. A better understanding of the role of sleep in plasma Aβ levels in aMCI patients could lead to effective sleep-based intervention against the risk of Alzheimer’s disease.

This study aims to investigate the extent to which sleep duration and efficiency are associated with plasma amyloid-β (Aβ) levels in non-demented older people. This study is a cross-sectional analysis of 305 non-demented older people. Sleep duration and efficiency were assessed used the Pittsburgh Sleep Quality Index. Levels of plasma Aβ were determined by sandwich enzyme-linked immunosorbent assay technique. Associations between sleep variables and plasma Aβ levels were evaluated with multivariable linear regression analysis. Compared to those with sleep duration > 7 h, participants with sleep duration < 6 h had a higher plasma Aβ42 level (β = 0.495, 95% CI 0.077~0.913, p = 0.021) and Aβ42/Aβ40 ratio (β = 0.101, 95% CI 0.058~0.144, p < 0.001). Compared to those with sleep efficiency ≥ 85%, participants with lower sleep efficiency (65~74%

Objectives: To characterize gait disorders in patients with amnestic mild cognitive impairments and determine the association between the performance of the gait function and cognition. Methodology: In this study, we enrolled 38 patients with amnestic mild cognitive impairment (aMCI) and 30 cognitively normal individuals (NC). Neuropsychological assessments included tests of memory, executive function, language, and attention. Using an inertial-sensor-based wearable instrument, we collected the gait data dynamically for at least 1 h/day for 2 weeks. The gait parameters included walking velocity, stride length, stride time, cadence, and stride time variability. Results: The aMCI patients had reduced walking velocity and stride length and increased stride time variability compared with the NCs. Walking velocity was positively correlated with long-term memory (r = 0.256, p = 0.043) and executive function (r = 0.490, p = 0.007). Stride length was positively correlated with long-term memory (r = 0.322, p = 0.036), executive function (r = 0.366, p = 0.024), and attention (r = 0.264, p = 0.048). Stride time variability was negatively correlated with long-term memory (r = −0.206, p = 0.038), executive function (r = −0.430, p = 0.022), and attention (r = −0.247, p = 0.015). Conclusion: This study suggested that cognitive impairment-related gait disorders occur (reduced gait speed, gait length, and gait stability) in daily life walking among the aMCI patients. A sensor-based wearable device for gait measurement may be an alternative and convenient tool for screening cognitive impairment.

Lipids are essential to brain functions, yet they remain largely unexplored. Here we investigated the lipidome composition of prefrontal cortex gray matter in 396 cognitively healthy individuals with ages spanning 100 years, as well as 67 adult individuals diagnosed with autism (ASD), schizophrenia (SZ), and Down syndrome (DS). Of the 5024 detected lipids, 95% showed significant age-dependent concentration differences clustering into four temporal stages, and resulting in a gradual increase in membrane fluidity in individuals ranging from newborn to nonagenarian. Aging affects 14% of the brain lipidome with late-life changes starting predominantly at 50–55 years of age—a period of general metabolic transition. All three diseases alter the brain lipidome composition, leading—among other things—to a concentration decrease in glycerophospholipid metabolism and endocannabinoid signaling pathways. Lipid concentration decreases in SZ were further linked to genetic variants associated with disease, indicating the relevance of the lipidome changes to disease progression.

The aim of this study was to investigate the mechanisms and effects of B-cell lymphoma 2 (Bcl-2) on the vasculogenic mimicry (VM) of human glioma cells. U87 cells were cultured under hypoxic conditions and then divided into four groups: Control, 3-(5-hydroxymethyl-2-furyl)-1-benzylindazole (YC-1), ABT-737 and YC-1 + ABT-737. These groups were treated with the corresponding simulators. The expression of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-14 and Bcl-2 in each group was determined using a reverse transcription-quantitative polymerase chain reaction and western blot analysis. Compared with that in the control group, the mRNA and protein expression of MMP-2, MMP-14 and Bcl-2 in the YC-1 and ABT-737 groups was significantly reduced. The expression of HIF-1α, however, was only significantly reduced in the YC-1 group (P

The purpose of the present study was to characterize the expressions of phosphorylated Ca(2+)/calmodulin-dependent protein kinase II (p-CaMK-II), total CaMK-II, and L-type Ca(2+) channel in offspring hippocampus that was induced by prenatal restraint stress. Pregnant rats were divided into two groups: the control group and the prenatal stress (PNS) group. Pregnant rats in the PNS group were exposed to restraint stress on day 14-20 of pregnancy three times daily for 45 min. Adult offspring rats were used in this study. The results demonstrated that prenatal restraint stress induced a significant increase in the expression of p-CaMK-II, total CaMK-II, and L-Ca(2+) channel by western blot analysis in offspring hippocampus. The immunohistochemistry results revealed that PNS increased the expressions of CaMK-II and L-Ca(2+) channel in the hippocampal CA3 of offspring rats. These data suggest that PNS can have long-term neuronal effects within hippocampal structure involved in the feedback mechanisms of the hypothalamo-pituitary-adrenal axis.

The hippocampus, which has the highest density of GC receptors in the brain, is involved in the regulation of the HPA and the behavioral responses to stress. Overexposure to corticosteroid hormones is harmful to hippocampal neuron integrity. Our purpose is to investigate the effects of prenatal stress (PNS) on expression of p38 mitogen-activated protein kinase (p38 MAPK) in offspring hippocampal neurons using Western blotting and Immunohistochemistry. The prenatal restraint stress induces significant increase in the expression of p-p38 MAPK and total p38 MAPK in female offspring hippocampus. The level of p-p38 MAPK in PNS female offspring rats was significantly increased (126.41 ± 3.937, n = 6) compared with that in the control female offspring rats (101.35 ± 3.468, n = 6, P < 0.01). Immunoblot analysis revealed there was significant difference in the level of total p38 MAPK between the female control and prenatal restraint stress offspring rats (101.70 ± 3.162 vs. 128.111 ± 2.724, respectively, P < 0.01). Immunodensity of p38 MAPK was significantly increased above female control in PNS female offspring hippocampal CA3 and CA4 fields (P < 0.001 vs. control group, CON). The data suggest that exposure of animals to a period of stressful experience during a critical phase could impose lasting effects on the offspring hippocampal neurons cellular signalling of offspring hippocampus.

Prenatal stress is known to cause neuronal loss and oxidative damage in the hippocampus of offspring rats. The underlying molecular mechanism has not been fully understood. The extracellularsignal-regulated kinase (ERK1/2) is recruited when the brain undergoes synaptic plasticity and remodeling. In the present study, we used Western blotting and immunohistochemistry techniques to examine the effects of prenatal restraint stress (PNS) on the expression of phosphorylated ERK (p-ERK) and total ERK. Pregnant rats in the PNS group were exposed to restraint stress on day 14–20 of pregnancy three times daily for 45 min. One-month-old offspring rats were used in this experiment. PNS treatment increased the expression of p-ERK2 compared to that in the control female offspring rats and total ERK2 in female offspring hippocampus compared with that of control group. No significant changes in the amounts of total ERK1 of prenatally offspring hippocampus were observed in both genders compared with control animals. ERK immunodensity was significantly increased in PNS groups in CA3 field in male offspring hippocampus compared with control animals. ERK optical density was significantly increased in PNS female offspring hippocampus CA1, CA3 and CA4 region. However, ERK optical density was not significantly different between male control and PNS groups in CA1, CA4 fields and DG in offspring hippocampus. These findings suggest the sex and region-dependent effects of prenatal stress on the expression of ERK in offspring hippocampus. ERK expression changes induced by prenatal stress may contribute to hippocampus synaptic plasticity changes of the offspring.

The mammalian target of rapamycin (mTOR) is a crucial regulator in malignant gliomas. Vasculogenic mimicry (VM) describes functional channels established by highly malignant tumor cells that is different from endothelium-lined blood vessels. Our previous studies confirmed the existence and clinical significance of VM in medulloblastoma and glioblastoma. In the present study, by immunohistochemical and CD34/PAS histochemical double-staining, 34 cases (26.8%) with VM structures were identified among a total of 127 glioma cases, and these VM structures were associated with mTOR expression in the glioma specimens. In vitro, U87 malignant glioblastoma cells formed tube structures similar to HUVECs on Matrigel in 3D culture, and mTOR-specific inhibitor rapamycin inhibited VM formation in the U87 malignant glioblastoma cells under both normoxia and hypoxia. In addition, rapamycin and mTOR siRNA inhibited molecules in the signaling cascade of VM formation, particularly HIF-1α. Taken together, our results demonstrated that mTOR signaling is involved in VM formation, and may be a potential therapeutic target for gliomas.