多学科合作诊疗系统治疗孕妇心理问题诱发的躯体功能障碍临床回顾性研究

目的 探讨孕产妇由心理问题诱发的躯体功能障碍[孕产期心身障碍(PSD)]临床创新技术疗效.方法 对2016年1月至2017年2月在天津市滨海新区大港妇女儿童保健中心、广州市越秀区妇幼保健院、烟台市烟台山医院、天津市河北区妇女儿童保健和计划生育服务中心、临安市妇幼保健计划生育服务中心、扬州市妇幼保健院孕产妇心身健康门诊研究基地应用多学科合作模式的生理调控、心理调节、音乐调理(PPM)干预措施(基于产科)治疗罹患孕产期PSD的283例孕妇的临床疗效进行回顾性分析.结果 治疗显效率为60.78%(172/283),治疗有效率为31.44%(89/283);治疗无效率为7.78%(22/283);总有效率为92.23%(261/283).结论 应用多学科合作模式的PPM干预措施(基于产科)治疗孕产期PSD,疗效显著;同时对焦虑、抑郁亦起到治疗作用.     

Homers regulate drug-induced neuroplasticity: implications for addiction

Drug addiction is a chronic, relapsing disorder, characterized by an uncontrollable motivation to seek and use drugs. Converging clinical and preclinical observations implicate pathologies within the corticolimbic glutamate system in the genetic predisposition to, and the development of, an addicted phenotype. Such observations pose cellular factors regulating glutamate transmission as likely molecular candidates in the etiology of addiction. Members of the Homer family of proteins regulate signal transduction through, and the trafficking of, glutamate receptors, as well as maintain and regulate extracellular glutamate levels in corticolimbic brain regions. This review summarizes the existing data implicating the Homer family of protein in acute behavioral and neurochemical sensitivity to drugs of abuse, the development of drug-induced neuroplasticity, as well as other behavioral and cognitive pathologies associated with an addicted state.     

Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats

The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6–15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed–adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage.     

海坤失眠治疗仪配合心理疏导治疗卒中后失眠疗效观察

目的 观察海坤失眠治疗仪联合心理疏导治疗卒中后失眠的效果。方法 110例纳入患者随机分为两组,常规中西医对症基础治疗,对照组54例采用海坤失眠治疗仪治疗,观察组56例再联合心理疏导干预,每日1次,每周6次,连续治疗2周。结果 观察组总有效54例(96.43%),对照组总有效47例(87.04%)。两组具有显著性差异(P＜0.05)。结论 海坤失眠治疗仪联合心理疏导治疗卒中后失眠效果肯定,提示心理干预有良好的改善睡眠作用。     

Organization of amyloid‐β protein precursor intracellular domain‐associated protein‐1 in the rat brain

Sustained activity‐dependent synaptic modifications require protein synthesis. Although proteins can be synthesized locally in dendrites, long‐term changes also require nuclear signaling. Amyloid‐β protein precursor intracellular domain‐associated protein‐1 (AIDA‐1), an abundant component of the biochemical postsynaptic density fraction, contains a nuclear localization sequence, making it a plausible candidate for synapse‐to‐nucleus signaling. We used immunohistochemistry to study the regional, cellular, and subcellular distribution of AIDA‐1. Immunostaining was prominent in the hippocampus, cerebral cortex, and neostriatum. Along with diffuse staining of neuropil, fluorescence microscopy revealed immunostaining of excitatory synapses throughout the forebrain, and immunoreactive puncta within and directly outside the nucleus. Presynaptic staining was conspicuous in hippocampal mossy fibers. Electron microscopic analysis of material processed for postembedding immunogold revealed AIDA‐1 label within postsynaptic densities in both hippocampus and cortex. Together with previous work, these data suggest that AIDA‐1 serves as a direct signaling link between synapses and the nucleus in adult rat brain. J. Comp. Neurol. 518:3221–3236, 2010. © 2010 Wiley‐Liss, Inc.     

小檗碱对三转基因阿尔茨海默病小鼠的学习记忆和海马PSD95突触相关蛋白表达水平的影响

目的 探讨小檗碱(BBR)对三转基因阿尔茨海默病(AD)小鼠的学习记忆及海马组织PSD95突触蛋白表达水平的影响。方法 将30只三转基因(APP/Tau/PS1)AD小鼠按随机数字表法分成3组,即AD对照组、AD+25 mgBBR组、AD+50 mgBBR,每组各10只,后2组以灌胃方式且剂量分别为25 mg·kg^-1·d^-1、50 mg·kg^-1·d^-1,对照组给予等剂量生理盐水连续3个月灌胃处理; 采用Morris水迷宫方法探测各组AD小鼠行为学改变、空间记忆及探索情况; 免疫荧光染色检测各组小鼠海马组织突触后致密蛋白95(PSD95)阳性表达水平; Western blotting(WB)法检测各组三转基因AD小鼠海马脑组织PSD95蛋白、磷酸化蛋白激酶B(p-Akt)和磷酸化雷帕霉素靶蛋白(p-mTOR)表达水平及微管相关蛋白轻链3-Ⅱ(LC3-Ⅱ)自噬水平。结果 AD+25 mgBBR组的逃避潜伏期的学习记忆能力、免疫荧光PSD95表达水平以及PSD995、LC3-Ⅱ、p-Akt、p-mTOR蛋白表达水平与AD对照组比较均有明显差异(P<0.05); AD+50 mgBBR组逃避潜伏期的学习记忆能力、免疫荧光PSD95表达水平以及LC3-Ⅱ、p-Akt、p-mTOR表达水平与AD对照组比较差异均更明显(P<0.05,P<0.01)。结论 应用50 mg小檗碱能较好改善三转基因AD小鼠的学习记忆、空间探索能力,其机制可能是通过增加自噬水平LC3-Ⅱ调控Akt/mTOR信号通路,增加突触蛋白PSD95的表达水平及突触数量,以改善AD相关临床症状。     

Pallidal deep brain stimulation modulates excessive cortical high β phase amplitude coupling in Parkinson disease

Objective

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and globus pallidus internus (GPi) are equally efficacious in the management of Parkinson disease (PD). Studies of STN-DBS have revealed a therapeutic reduction in excessive cortical β-γ phase-amplitude coupling (PAC). It is unclear whether this is specific to STN-DBS and potentially mediated by modulation of the hyperdirect pathway or if it is a generalizable mechanism seen with DBS of other targets. Moreover, it remains unclear how cortical signals are differentially modulated by movement versus therapy. To clarify, the effects of GPi-DBS and movement on cortical β power and β-γ PAC were examined.

TGF‐β2 and TGF‐β3 from cultured β‐amyloid‐treated or 3xTg‐AD‐derived astrocytes may mediate astrocyte–neuron communication

Astrocytes participate in the development and resolution of neuroinflammation in numerous ways, including the release of cytokines and growth factors. Among many, astrocytes release transforming growth factors beta (TGF‐β) TGF‐β1, TGF‐β2 and TGF‐β3. TGF‐β1 is the most studied isoform, while production and release of TGF‐β2 and TGF‐β3 by astrocytes have been poorly characterized. Here, we report that purified cultures of hippocampal astrocytes produce mainly TGF‐β3 followed by TGF‐β2 and TGF‐β1. Furthermore, astrocytes release principally the active form of TGF‐β3 over the other two. Changes in release of TGF‐β were sensitive to the calcineurin (CaN) inhibitor FK506. Starvation had no effect on TGF‐β1 and TGF‐β3 while TGF‐β2 mRNA was significantly up‐regulated in a CaN‐dependent manner. We further investigated production and release of astroglial TGF‐β in Alzheimer's disease‐related conditions. Oligomeric β‐amyloid (Aβ) down‐regulated TGF‐β1, while up‐regulating TGF‐β2 and TGF‐β3, in a CaN‐dependent manner. In cultured hippocampal astrocytes from 3xTg‐AD mice, TGF‐β2 and TGF‐β3, but not TGF‐β1, were up‐regulated, and this was CaN‐independent. In hippocampal tissues from symptomatic 3xTg‐AD mice, TGF‐β2 was up‐regulated with respect to control mice. Finally, treatment with recombinant TGF‐βs showed that TGF‐β2 and TGF‐β3 significantly reduced PSD95 protein in cultured hippocampal neurons, and this effect was paralleled by conditioned media from Aβ‐treated astrocytes or from astrocytes from 3xTg‐AD mice. Taken together, our data suggest that TGF‐β2 and TGF‐β3 are produced by astrocytes in a CaN‐dependent manner and should be investigated further in the context of astrocyte‐mediated neurodegeneration.     

Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms

ObjectiveRecent discoveries suggest that it is most likely the coupling of β oscillations (13–30 Hz) and not merely their power that relates to Parkinson disease (PD) pathophysiology.MethodsWe analyzed power and phase amplitude coupling (PAC) in local field potentials (LFP) recorded from Pallidum after placement of deep brain stimulation (DBS) leads in nineteen PD patients and three patients with dystonia.ResultsWithin GPi, we identified PAC between phase of β and amplitude of high frequency oscillations (200–300 Hz) and distinct β-low γ (40–80 Hz) PAC both modulated by contralateral movement. Resting β-low γ PAC, also present in dystonia patients, inversely correlated with severity of rigidity and bradykinesia (R = −0.44, P = 0.028). These findings were specific to the low β band, suggesting a differential role for the two β sub-bands.ConclusionsPAC is present across distinct frequency bands within the GPi. Given the presence of low β-low γ PAC in dystonia and the inverse correlation with symptom severity, we propose that this PAC may be a normal pallidal signal.SignificanceThis study provides new evidence on the pathophysiological contribution of local pallidal coupling and suggests similar and distinct patterns of coupling within GPi and STN in PD.