Non-serine-phosphorylated tyrosine hydroxylase expressing neurons are present in mouse striatum,accumbens and cortex that increase in number following dopaminergic denervation

Neurons partially expressing individual enzymes of dopamine (DA) biosynthesis, e.g. tyrosine hydroxylase (TH) or aromatic acid decarboxylase, are found in different areas of the central nervous system, continuously or transiently in normal and pathological conditions. This current study analyzed if TH neurons exist in target areas of ventral midbrain dopaminergic neurons and how they react to dopaminergic denervation.High power analysis of brain tissue sections revealed that TH-immunopositive neurons were present in striatum, accumbens and cortex - and several other brain areas - of healthy adult mice. DAergic denervation induced by stereotaxic injection of 6-hydroxydopamine into the medial forebrain bundle increased the number of TH expressing neurons in the striatum, accumbens and the cortex, up 40 d later. These TH neurons were not stained by specific antibodies recognizing TH phosphorylated at serine residues 19, 31 and 40, dopamine transporter and vesicular monoamine transporter type 2, but most of them expressed dopamine and cyclic AMP-regulated phosphoprotein 32 kDa.Thus, mouse striatum, accumbens and cortex contain neurons which express TH with low activity, and their number increases following dopamine depletion.     

Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T‐cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1^hi) develop normally in immunocompetent and Rag2^?/?thymi, their differentiation is partially blocked in Rag2^?/?Il2rg^?/? counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross‐talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)⁺ mTEC subtypes expressing intermediate CCRL1 levels (CCRL1^int) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2^?/? thymi, CCRL1^int mTECs are restored in Rag2^?/?Marilyn TCR‐Tg mice, indicating that the appearance of postnatal‐restricted mTECs is closely linked with T‐cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.     

CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells

Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs), which play essential roles in the establishment of a functionally competent and self‐tolerant repertoire of T cells, are derived from common thymic epithelial progenitor cells (pTECs). Recent findings indicate that mTECs are derived from cells that express molecules that are abundant in cTECs rather than mTECs, and provide fresh insight into the characteristics of pTECs and their diversification pathways into TEC subpopulations. In this issue of the European Journal of Immunology, Ribeiro et al. [Eur. J. Immunol. 2014. 44: 2918–2924] focus on CCRL1, an atypical chemokine receptor that is highly expressed by cTECs rather than mTECs, and show that CCRL1‐expressing embryonic TECs can give rise to mTECs. Interestingly, Ribeiro et al. further report that a fraction of postnatal mTECs express CCRL1 at a low level, suggesting novel complexity in mTECs.     

Accelerated aging of selective brain structures in human immunodeficiency virus infection: a controlled,longitudinal magnetic resonance imaging study

Advances in treatment have transformed human immunodeficiency virus (HIV) infection from an inexorable march to severe morbidity and premature death to a manageable chronic condition, often marked by good health. Thus, infected individuals are living long enough that there is a potential for interaction with normal senescence effects on various organ systems, including the brain. To examine this interaction, the brains of 51 individuals with HIV infection and 65 uninfected controls were studied using 351 magnetic resonance imaging and a battery of neuropsychological tests collected 2 or more times over follow-up periods ranging from 6 months to 8 years. Brain tissue regions of interest showed expected age-related decrease in volume; cerebrospinal fluid-filled spaces showed increase in volume for both groups. Although HIV-infected individuals were in good general health, and free of clinically-detectable dementia, several brain regions supporting higher-order cognition and integration of functions showed acceleration of the normal aging trajectory, including neocortex, which extended from the frontal and temporal poles to the parietal lobe, and the thalamus. Beyond an anticipated increase in lateral ventricle and Sylvian fissure volumes and decrease in tissue volumes (specifically, the frontal and sensorimotor neocortices, thalamus, and hippocampus) with longer duration of illness, most regions also showed accelerated disease progression. This accelerated loss of cortical tissue may represent a risk factor for premature cognitive and motor compromise if not dementia. On a more promising note, HIV-infected patients with increasing CD4 counts exhibited slower expansion of Sylvian fissure volume and slower declines of frontal and temporoparietal cortices, insula, and hippocampus tissue volumes. Thus, attenuated shrinkage of these brain regions, likely with adequate pharmacologic treatment and control of further infection, has the potential of abating decline in associated higher-order functions, notably, explicit memory, executive functions, self-regulation, and visuospatial abilities.     

铁皮石斛中多糖和甘露糖含量测定方法的改进及与齿瓣石斛的比较研究

目的：改进铁皮石斛中多糖和甘露糖的含量测定方法并对铁皮石斛与齿瓣石斛中的多糖和甘露糖含量进行分析比较。方法：采用硫酸-苯酚法测定石斛中多糖的含量;采用高效液相色谱法测定石斛中甘露糖的含量。结果：多糖在2.54～12.87 mg· L-1范围线性关系良好（r＝0.9990）,平均回收率为99.02％,RSD为2.6％（n＝6）;甘露糖的平均回收率为101.5％,RSD为1.7％（n＝9）。6批铁皮石斛药材多糖平均含量为45.94％,甘露糖平均含量为32.33％;9批齿瓣石斛药材多糖平均含量为45.12％,甘露糖平均含量为37.88％。结论：所建方法操作比较简单,准确可靠,重现性好,可用于控制铁皮石斛的质量。铁皮石斛与齿瓣石斛多糖含量相当,齿瓣石斛甘露糖含量高于铁皮石斛。     

功能性消化不良患者水负荷试验时大脑感知作用的fMRI研究

背景：应用功能性核磁共振成像（fMRI）可提示内脏感觉转导作用和内脏高敏感的中枢机制。目前水负荷试验（WLT）致中枢反应的fMRI研究尚少见。目的：研究功能性消化不良（FD）患者WLT时大脑皮质的信息反应特点,探讨其内脏高敏感的中枢机制。方法：纳入符合罗马Ⅲ标准的11例餐后不适综合征（PDS）、13例上腹痛综合征（EPS）患者以及12名对照者。受试者行WLT时接受fMRI检查。结果：PDS和EPS组胃初次饱足阈值、最大饱足阈值均显著低于对照者（P〈0.05）。三组激活脑区大部分集中于双侧大脑半球的前扣带回、颞叶、额叶、岛叶（左侧为主）、楔叶（左侧为主）、丘脑、小脑。PDS组胃初次饱足时颞叶、小脑以及最大饱足时小脑、岛叶的fMRI最大信号变化幅度均显著高于对照者（P〈0.05）;EPS组胃初次饱足时以及最大饱足时前扣带回、枕叶均显著高于对照者（P〈0.05）;除最大饱足时枕叶外,两个FD亚组之间均无明显差异（P〉0.05）。结论：WLT时FD患者大脑感知作用可能与健康对照者相似,中枢在边缘系统（主要为岛叶、前扣带回）以及颞叶、小脑、枕叶等脑区的加工、处理或调节存在异常,导致内脏敏感性增高：而FD亚型之间无明显差异。     

肉桂油对胰岛素抵抗小鼠糖脂代谢的影响

目的:研究肉桂油对胰岛素抵抗小鼠糖脂代谢的影响,探讨其作用机制.方法:采用高脂饲料喂养建立小鼠胰岛素抵抗模型,经肉桂油治疗后测定口服糖耐量及胰岛素耐受,观察体质量、血糖、血清胰岛素、甘油三酯、总胆固醇、瘦素、抵抗素、脂联素的变化.结果:肉桂油能降低胰岛素抵抗小鼠的体质量(30.3±3.6vs34.6±3.1,P<0.05)、血糖(7.6±2.2vs9.2±1.3,P<0.05)、血清胰岛素(1.3±0.1vs1.7±0.2,P<0.05)、甘油三酯(70.1±10.9vs65.4±19.5,P<0.05)、总胆固醇(93.2±13.8vs102.3±21.5,P<0.05)、瘦素、抵抗素水平,同时改善口服糖耐量,降低胰岛素抵抗.结论:肉桂油能有效改善胰岛素抵抗小鼠糖脂代谢,其作用与降低血清瘦素、抵抗素水平,增加胰岛素敏感性有关.