Downregulation of thioredoxin reductase 1 expression in the substantia nigra pars compacta of Parkinson's disease mice

Because neurons are susceptible to oxidative damage and thioredoxin reductase 1 is extensively distributed in the central nervous system and has antioxidant properties, we speculated that the enzyme may be involved in the pathogenesis of Parkinson＇s disease. A Parkinson＇s disease model was produced by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into C57BL/6 mice. Real-time reverse transcription-PCR, western blot analysis and colorimetric assay showed that the levels of thioredoxin reductase 1 mRNA and protein were decreased, along with a significant reduction in thioredoxin reductase activity, in the midbrain of Parkinson＇s disease mice compared with normal mice. Immunohistochemical staining revealed that the number of thioredoxin reductase 1-positive neurons in the substantia nigra pars compacta of Parkinson＇s disease mice was significantly decreased compared with normal mice. These experimental findings suggest that the expression of thioredoxin reductase 1 in the substantia nigra pars compacta of Parkinson＇s disease mice is significantly decreased, and that the enzyme may be associated with disease onset.

Ontogenesis of the Form <i>Biota orientalis compacta</i>(Cupressaceae) in the Conditions of Introduction of the Tashkent Botanical Garden (Uzbekistan)

The ontogenesis of the form Biota orientalis compacta (Cupressaceae) was first studied in the conditions of introduction of the Tashkent Botanical Garden. The passage of periods and stages of ontogenesis, full ripening of the cones, a high rate of growth and development, as well as high seed productivity are the main indicators of the success and prospects of the introduction of the form Biota orientalis compacta. The data obtained will serve as a theoretical basis for the agrotechnical development in landscaping.

B&K公司订购高宝(KBA)Compacta217商业印刷机——高宝(KBA)在德国热销

位于0ttersweier的德国印刷企业B＆KOffsetdruck公司雄心勃勃,希望扩大其市场份额,它已经订购了一套高宝(K BA)C om pacta217高性能16页式的商业印刷机.自35年前创建以来,B&K公司在专门从事产品定制和提供一站武服务方面,从设计开发到印刷产品的转化,一直在稳步壮大,这个家族企业共有250名员工,他们在操纵先进设备时展示出非凡的技能和丰富的经验.

高宝商业轮转胶印机——面向短版彩色杂志印刷的COMPACTA 215

适用于短版及中版活印刷的高宝COMPACTA215 毫疑问,卷筒纸商业印刷的趋势是短版活及中版活日益增多,此外,这一领域还存在着激烈的价格竞争.如今的卷筒纸胶印机必须能尽量缩短准备时间,降低废品率,适印范围广,印刷质量高,能很经济地运行,操作简便,并能通过各种自动化装置减低人的劳动强度.高宝COM-PACTA 21 5能最大程度地满足上述要求,是印速为每小时5万份的同类机型中最先进的商用卷筒纸胶印机之一.

高宝Compacta 215商用卷筒纸胶印机

高宝Compacta 215型商用卷筒纸胶印机采用高宝公司推出的一项新技术,该机印刷质量高,经济效益好.

即将于德鲁巴2004推出的新型16页Compacta——KBA Heatset家族喜添新成员

KBA发布了即将于德鲁巴2004展示的另一款新产品——70，000cph高自动化商用卷筒纸印刷机Compacta217的细节。该机型将瞄准高端的16页市场，并为世界首台无轴印刷机1997-vintage Compacta215提供补充，从而扩大在中型印刷机的市场份额。

Activation and polarization of striatal microglia and astrocytes are involved in bradykinesia and allodynia in early-stage parkinsonian mice

In addition to the cardinal motor symptoms,pain is a major non-motor symptom of Parkinson's disease(PD).Neuroinflammation in the substantia nigra pars compacta and dorsal striatum is involved in neurodegeneration in PD.But the polarization of microglia and astrocytes in the dorsal striatum and their contribution to motor deficits and hyperalgesia in PD have not been characterized.In the present study,we observed that hemiparkinsonian mice established by unilateral 6-OHDA injection in the medial forebrain bundle exhibited motor deficits and mechanical allodynia.In these mice,both microglia and astrocytes in the dorsal striatum were activated and polarized to M1/M2 microglia and A1/A2 astrocytes as genes specific to these cells were upregulated.These effects peaked 7 days after 6-OHDA injection.Meanwhile,striatal astrocytes in parkinsonian mice also displayed hyperpolarized membrane potentials,enhanced voltage-gated potassium currents,and dysfunction in inwardly rectifying potassium channels and glutamate transporters.Systemic administration of minocycline,a microglia inhibitor,attenuated the expression of genes specific to M1 microglia and A1 astrocytes in the dorsal striatum(but not those specific to M2 microglia and A2 astrocytes),attenuated the damage in the nigrostriatal dopaminergic system,and alleviated the motor deficits and mechanical allodynia in parkinsonian mice.By contrast,local administration of minocycline into the dorsal striatum of parkinsonian mice mitigated only hyperalgesia.This study suggests that M1 microglia and A1 astrocytes in the dorsal striatum may play important roles in the development of pathophysiology underlying hyperalgesia in the early stages of PD.

The raphe nuclei are the early lesion site of gastric α-synuclein propagation to the substantia nigra

Parkinson's disease(PD)is a neurodegeneration disease withα-synuclein accumulated in the substantia nigra pars compacta(SNpc)and most of the dopaminergic neurons are lost in SNpc while patients are diagnosed with PD.Exploring the pathology at an early stage contributes to the development of the disease-modifying strategy.Although the“gut–brain”hypothesis is proposed to explain the underlying mechanism,where the earlier lesioned site in the brain of gastricα-synuclein and howα-synuclein further spreads are not fully understood.Here we report that caudal raphe nuclei(CRN)are the early lesion site of gastricα-synuclein propagating through the spinal cord,while locus coeruleus(LC)and substantia nigra pars compacta(SNpc)were further affected over a time frame of 7 months.Pathologicalα-synuclein propagation via CRN leads to neuron loss and disordered neuron activity,accompanied by abnormal motor and non-motor behavior.Potential neuron circuits are observed among CRN,LC,and SNpc,which contribute to the venerability of dopaminergic neurons in SNpc.These results show that CRN is the key region for the gastricα-synuclein spread to the midbrain.Our study provides valuable details for the“gut–brain”hypothesis and proposes a valuable PD model for future research on early PD intervention.

Super Weak Compactness and Uniform Eberlein Compacta

We prove that a topological space is uniform Eberlein compact iff it is homeomorphic to a super weakly compact subset C of a Banach space such that the closed convex hull coC of C is super weakly compact. We also show that a Banach space X is super weakly compactly generated iff the dual unit ball B;of X;in its weak star topology is affinely homeomorphic to a super weakly compactly convex subset of a Banach space.

THE ANTAGONISTIC EFFECTS OF TETRAHYDRO-PROTOBERBERINES ON DOPAMINE RECEPTORS: ELECTROPHYSIOLOGICAL STUDIES

Tetrahydroprotoberberines (THPBs), including (-)-stepholidine ((-)-SPD), (-)-tetrahydropalmatine ((-)-THP) and tetrahydroberberine (THB), have been demonstrated to be a new class of DA antagonists in biochemical and neuropharmacological studies. In this paper, the antagonistic action of THPBs was examined by means of single unit recording from nigral DA neuron in chloral hydrate-anesthetized and gallamine-paralyzed rats. Intravenous injection of these compounds could promptly and completely reverse the inhibition of the spontaneous firing induced by DA agonist apomorphine (APO) in a dose-dependent way. Pretreatment with (-)-SPD, (-)-THP or THB could significantly reduce the inhibitory effect of APO and shift the dose-action curve to the right. Besides, the compounds could increase the spontaneous firing of DA neurons. The above results not only strongly support the conclusion that (-)-SPD, (-)-THP and THB are DA antagonists, but also demonstrate that one of their blocking sites is at somatodendritic DA autoreceptors (D-2 receptors). In other words, (-)-SPD did not exhibit any DA agonistic action in this acute electrophysiological study, although its DA agonistic action can be demonstrated in rotational behavior of 6-oHDA-lesioned rats. The dual actions of (-)-SPD, dependent upon different experimental conditions, are discussed.

Aldehyde Dehydrogenase 1 making molecular inroads into the differential vulnerability of nigrostriatal dopaminergic neuron subtypes in Parkinson’s disease

A preferential dysfunction/loss of dopaminergic(DA)neurons in the substantia nigra pars compacta(SNpc)accounts for the main motor symptoms of Parkinson’s disease(PD),the most common degenerative movement disorder.However,the neuronal loss is not stochastic,but rather displays regionally selectivity,indicating the existence of different DA subpopulations in the SNpc.To identify the underlying molecular determinants is thereby instrumental in understanding the pathophysiological mechanisms of PD-related neuron dysfunction/loss and offering new therapeutic targets.Recently,we have demonstrated that aldehyde dehydrogenase 1(ALDH1A1)is one such molecular determinant that defines and protects an SNpc DA neuron subpopulation preferentially affected in PD.In this review,we provide further analysis and discussion on the roles of ALDH1A1 in the function and survival of SNpc DA neurons in both rodent and human brains.We also explore the feasibility of ALDH1A1 as a potential biomarker and therapeutic target for PD.