Modeling oxidative stress in the central nervous system

Oxidative stress is associated with the onset and pathogenesis of several prominent central nervous system disorders. Consequently, there is a pressing need for experimental methods for studying neuronal responses to oxidative stress. A number of techniques for modeling oxidative stress have been developed, including the use of inhibitors of the mitochondrial respiratory chain, depletion of endogenous antioxidants, application of products of lipid peroxidation, use of heavy metals, and models of ischemic brain injury. These experimental approaches can be applied from cell culture to in vivo animal models. Their use has provided insight into the molecular underpinnings of oxidative stress responses in the nervous system, including cell recovery and cell death. Reactive oxygen species contribute to conformational change-induced activation of signaling pathways, inactivation of enzymes through modification of catalytic cysteine residues, and subcellular redistribution of signaling molecules. In this review, we will discuss several methods for inducing oxidative stress in the nervous system and explore newly emerging concepts in oxidative stress signaling.     

Regulation of proliferation during central nervous system development

The retina is one of the best-characterized regions of the central nervous system (CNS) and has served as a model for many of the principles that now form the foundation for CNS development. In the past several years, a number of advances have been made in our understanding of the coordination of proliferation and cell fate specification during retinal development. In this review, we will draw on findings from studies of the retina and highlight similarities and differences in other regions in the CNS, namely the cerebellum and cortex. We will present a framework in which to pose challenges and outstanding questions for future studies on the coordination of proliferation and cell fate specification in the developing CNS.     

Antibodies from inflamed central nervous system tissue recognize myelin oligodendrocyte glycoprotein

Autoantibodies to myelin oligodendrocyte glycoprotein (MOG) can induce demyelination and oligodendrocyte loss in models of multiple sclerosis (MS). Whether anti-MOG Abs play a similar role in patients with MS or inflammatory CNS diseases by epitope spreading is unclear. We have therefore examined whether autoantibodies that bind properly folded MOG protein are present in the CNS parenchyma of MS patients. IgG was purified from CNS tissue of 14 postmortem cases of MS and 8 control cases, including cases of encephalitis. Binding was assessed using two independent assays, a fluorescence-based solid-phase assay and a solution-phase RIA. MOG autoantibodies were identified in IgG purified from CNS tissue by solid-phase immunoassay in 7 of 14 cases with MS and 1 case of subacute sclerosing panencephalitis, but not in IgG from noninflamed control tissue. This finding was confirmed with a solution-phase RIA, which measures higher affinity autoantibodies. These data demonstrate that autoantibodies recognizing MOG are present in substantially higher concentrations in the CNS parenchyma compared with cerebrospinal fluid and serum in subjects with MS, indicating that local production/accumulation is an important aspect of autoantibody-mediated pathology in demyelinating CNS diseases. Moreover, chronic inflammatory CNS disease may induce autoantibodies by virtue of epitope spreading.     

组织型激肽释放酶及相关肽酶在中枢神经系统中的作用

组织型激肽释放酶1(kallikrein1,KLK1)和激肽释放酶相关肽酶(kallikrein-related peptidase 2～15,KLK2～15)是一类丝氨酸蛋白酶,具有广泛的生物学活性。在中枢神经系统中,它们不但在脑的生长、发育和学习记忆等方面起重要作用,同时也在多种脑部疾病中起重要作用,如帕金森病、痴呆、多发性硬化、肿瘤等,并在这些疾病的诊断、治疗和预后方面显示出潜在的应用价值。     

Plasmalogenase activity in normal and demyelinating tissue of the central nervous system

1. The plasmalogenase activity of brain was found to be associated with the white matter but was absent from myelin fractions. 2. Increased enzyme activity was found in demyelinating spinal cords from vitamin B₁₂-deficient monkeys and in white matter from a patient with multiple sclerosis.     

Studies of neurotransmitter chemistry of central nervous system neurons in primary tissue culture

Primary tissue culture methods have been applied to various areas of the central nervous system, including cerebral cortex, spinal cord, cerebellum, hippocampus, hypothalamus, striatum, mesencephalon, lower brain stem and retina. Experimental studies in vitro involving central neurotransmission are discussed here. Information gleaned from such studies impacts on neurotransmitter identification, neuronal development, patterns of receptor distribution, peptidergic transmission, transmitter metabolism, synaptogenesis and the regulation of synaptic development.     

Nogo在中枢神经损伤再生中的作用机制

Nogo是中枢神经系统（CNS）少突胶质细胞分泌的一种髓磷脂蛋白,它的主要功能是抑制损伤后轴突的再生,它含有两个完全独立的具有抑制活性的结构域：位于细胞内的amino—Nogo和位于细胞表面的Nogo-66。Nogo-66是通过与受体复合体NgR／p75／Lingo—1结合,触发Rho信号通路来发挥作用。Nogo及其信号转导机制日益成为CNS损伤再生的研究热点,就Nogo在CNS损伤再生中的作用机制作一综述。     

Differential spatial distribution and temporal regulation of tissue inhibitor of metalloproteinase mRNA expression during rat central nervous system development

The elucidation of the cellular and molecular mechanisms governing the maturation of the central nervous system (CNS) is rapidly emerging. Cell-cell and cell-matrix interactions play critical roles in all phases of developmental tissue remodeling. Throughout development, an intricate balance between extracellular matrix synthesis and degradation is preserved by the opposing actions of matrix metalloproteinases (MMPs) and their specific inhibitors, the tissue inhibitors of metalloproteinases (TIMPs). Although recent evidence suggests that TIMPs exert diverse cell biological functions distinct from their MMP-inhibitory activities, few studies have investigated MMP or TIMP expression during CNS development. The present report analyzes the mRNA expression of the four known TIMPs throughout the course of embryonic and postnatal rat CNS development. The results clearly demonstrate the unique spatial distribution and temporal regulation of TIMP expression and suggest a distinct role for each TIMP during CNS development.