Histamine metabolism and its role in central nervous system function

The present day data concerning biosynthesis, storage, release and inactivation of histamine in the brain of mammals are given. The possibility to regulate histamine of the action of physiologically active substances is discussed.     

Programming and reprogramming neuronal subtypes in the central nervous system

Recent discoveries in nuclear reprogramming have challenged the dogma that the identity of terminally differentiated cells cannot be changed. The identification of molecular mechanisms that reprogram differentiated cells to a new identity carries profound implications for regenerative medicine across organ systems. The central nervous system (CNS) has historically been considered to be largely immutable. However, recent studies indicate that even the adult CNS is imparted with the potential to change under the appropriate stimuli. Here, we review current knowledge regarding the capability of distinct cells within the CNS to reprogram their identity and consider the role of developmental signals in directing these cell fate decisions. Finally, we discuss the progress and current challenges of using developmental signals to precisely direct the generation of individual neuronal subtypes in the postnatal CNS and in the dish.     

Tenascin-R: role in the central nervous system

Tenascin-R (TN-R), a member of the tenascin family of extracellular matrix glycoproteins, is exclusive to the nervous system. It affects cell migration, adhesion and differentiation, although no remarkable clinical consequences have been shown in knock-out animal models. TN-R's expression pattern suggests a possible primary or secondary role in certain neurological problems including malformations, tumors and neurodegenerative disorders. This review summarizes the structure and molecular interactions of this molecule and discusses its function and possible roles in the central nervous system.     

The role of macrophage subpopulations in autoimmune disease of the central nervous system

Summary In this review the role of various subpopulations of macrophages in the pathogenesis of experimental autoimmune encephalomyetitis is discussed. Immunohistochemistry with macrophage markers shows that in this disease different populations of macrophages (i.e. perivascular cells, microglia and infiltrating blood-borne macrophages) are present in the central nervous system. These subpopulations partially overlap in some functional activity while other activities seem to be restricted to a distinct subpopulation, indicating that these subpopulations have different roles in the pathogenesis of encephalomyelitis. The studies discussed in this review reveal that immunocytochemical and morphological studies, combined with new techniques such asin situ nick translation and experimental approaches like the use of bone marrow chimeras and macrophage depletion techniques, give valuable information about the types and functions of cells involved in central nervous system inflammation. The review is divided in three parts. In the first part the experimental autoimmune encephalomyelitis model is introduced. The second part gives an overview of the origin, morphology and functions of the various subpopulations. In the third part the role of these subpopulations is discussed in relation to the various stages (i.e. preclinical, clinical and recovery) of the experimental disease.     

中枢神经系统铁代谢与帕金森病的关系

帕金森病病人黑质内铁含量增高,铁参与自由工的生成导致神经细胞死亡,因此脑内铁含量增高被认为参与了帕金森病的发病。但是黑质内铁异常增高的原因不清,因此对于脑内铁代谢的研究显得尤为重要。本文就脑内铁的摄取及铁代谢相关蛋白即铁蛋白、乳铁蛋白、铜蓝蛋白与帕金森病的关系作一简要综述。     

Biotin transport and metabolism in the central nervous system

The mechanisms by which biotin enters and leaves brain, choroid plexus and cerebrospinal fluid (CSF) were investigated by injecting [³H]biotin either intravenously or intraventricularly into adult rabbits. [³H]biotin, either alone or together with unlabeled biotin was infused at a constant rate into conscious rabbits. At 180 minutes, [³H]biotin had entered CSF, choroid plexus, and brain. In brain, CSF, and plasma, greater than 90% of the nonvolatile³H was associated with [³H]biotin. The addition of 400 mol/kg unlabeled biotin to the infusion syringe decreased the penetration of [³H]biotin into brain and CSF by approximately 70 percent. Two hours after an intraventricular injection, [³H]biotin was cleared from the CSF more rapidly than mannitol and minimal metabolism of the [³H]biotin had occurred in brain. However, 18 hours after an intraventricular injection, approximately 35% of the [³H]biotin remaining in brain had been covalently incorporated into proteins, presumably into carboxylase apoenzymes. These results show that biotin enters CSF and brain by saturable transport systems that do not depend on metabolism of the biotin. However, [³H]biotin is very slowly incorporated covalently into proteins in brain in vivo.     

阿片类物质在中枢神经系统的免疫调控作用

内源及外源性阿片具有调节神经元与胶质细胞的功能,这些调节具有保护或损伤脑功能的双重作用。吗啡具有促进受病毒复制及继发感染的作用。另一方面,阿片受体中的ｋａｐｐａ受体可能具有保护神经元的作用。更深层次的研究应是了解阿片通过什么机制作用在胶质细胞和神经元上,藉此以促进研制出具有明显疗效的新药。     

载脂蛋白E在神经系统中的作用

载脂蛋白Ｅ（ａｐｏＥ）在中枢神经系统（ＣＮＳ）生长发育,成熟衰老和损伤修复过程中发挥重要作用。其分子机制是：（１）稳定神经细胞骨架系统;（２）通过ａｐｏＥ受体途径调节神经细胞中胆固醇脂的运输和突触末梢的再生;（３）调控神经元之间及神经细胞与介质之间的相互作用;（４）调节神经细胞的Ｃａ＾２＋离子的平衡。     

Interactions between central nervous system and peripheral metabolic organs

Science China Life Sciences - According to Descartes, minds and bodies are distinct kinds of “substance”, and they cannot have causal interactions. However, in neuroscience, the two-way...     

Androgen and progesterone metabolism in the central and peripheral nervous system

This paper summarizes the most recent data obtained in the authors' laboratory on the metabolism of testosterone and progesterone in neurons, in the glia, and in neuroblastoma cells. The activities of the 5α-reductase (the enzyme that converts testosterone into dihydrotestosterone, DHT), and of the 3α-hydroxysteroid dehydrogenase (the enzyme that converts DHT into 5α-androstane-3α,17β-diol, 3α-diol) have been first evaluated in primary cultures of neurons, oligodendrocytes and type-1 and -2 astrocytes, obtained from the fetal or neonatal rat brain. All the cultures were used on the fifth day. The formation of DHT or 3α-diol was evaluated incubating the different cultures with labeled testosterone or DHT as substrates. The results obtained indicate that the formation of DHT takes place preferentially in neurons; however, type-2 astrocytes and oligodendrocytes also possess considerable 5α-reductase activity, while type-1 astrocytes show a much lower enzymatic concentration. A completely different localization was observed for 3α-hydroxysteroid dehydrogenase; the formation of 3α-diol appears to be prevalently, if not exclusively, present in type-1 astrocytes; 3α-diol is formed in very low yields by neurons, type-2 astrocytes and oligodendrocytes. The compartmentalization of two strictly correlated enzymes (5α-reductase and 3α-hydroxysteroid dehydrogenase) in separate central nervous system (CNS) cell populations suggests the simultaneous participation of neurons and glial cells in the 5α-reductive metabolism of testosterone. Subsequently it has been shown that, similarly to what happens when testosterone is used as the substrate, the 5α-reductase which metabolizes progesterone into 5α-pregnane-3,20-dione (DHP) shows a significantly higher activity in neurons than in glial cells; however, type-1 and -2 astrocytes as well as oligodendrocytes also possess some ability to 5α-reduce progesterone. On the other hand, 3α-hydroxysteroid dehydrogenase, the enzyme which converts DHP into 5α-pregnane-3α-ol-20-one, appears to be present mainly in type-1 astrocytes; much lower levels of this enzyme are present in neurons and in type-2 astrocytes. At variance with the previous results obtained using androgens as precursors, oligodendrocytes show considerable 3α-hydroxysteroid dehydrogenase activity, even if this is statistically lower than that present in type-1 astrocytes. The existence of isoforms of the enzyme involved in androgen and progesterone metabolism is discussed.Finally, the ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied incubating the cells in the presence of labeled testosterone or progesterone to measure, respectively, the formation of DHT or DHP (5α-reductase activity). 3α-Hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 3α-diol. The results demonstrate that undifferentiated neuroblastoma cells possess a significant 5α-reductase activity, as shown by the considerable conversion of testosterone into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), but not after differentiation induced by retinoic acid (RA). The 5α-reductase present in SH-SY5Y cells is also able to convert progesterone into DHP. In undifferentiated cell, this conversion is about 8 times higher than that of testosterone into DHT. Under the influences of TPA and RA, the formation of DHP follows the same pattern observed for that of DHT. SH-SY5Y cells also appear to possess the enzyme 3α-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3α-diol. This enzymatic activity is not altered following TPA-induced differentiation, and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful “in vitro” model for the study of the mechanisms involved in the control of androgen and progesterone metabolism in nervous cells.     

Degeneration and repair in central nervous system disease

Divergent disease triggers in neurodegeneration may induce convergent endogenous pathways in neuronal, glial and vascular elements as the central nervous system (CNS) attempts to compensate, remodel and recover. Dissecting these multicellular mechanisms and the integrative responses in cerebral blood flow and metabolism may allow us to understand the balance between injury and repair, validate new targets and define therapeutic time windows for neurodegeneration.     

Olfactory ensheathing cells: their role in central nervous system repair

The olfactory system is an unusual tissue in that it can support neurogenesis throughout life; permitting the in-growth and synapse formation of olfactory receptor axons into the central nervous system (CNS) environment of the olfactory bulb. It is thought that this unusual property is in part due to the olfactory glial cells, termed olfactory ensheathing cells (OECs), but also due to neuronal stem cells. These glial cells originate from the olfactory placode and possess many properties in common with the glial cells from the peripheral nervous system (PNS), Schwann cells. Recent data has suggested that olfactory ensheathing cells are a distinct glial cell type and possess properties, which might make them more suitable for transplant-mediated repair of central nervous system injury models. This paper reviews the biological properties of these cells and illustrates their use in central nervous system repair.     

Crucial role of granulocytic myeloid-derived suppressor cells in the regulation of central nervous system autoimmune disease

There is a need in autoimmune diseases to uncover the mechanisms involved in the natural resolution of inflammation. In this article, we demonstrate that granulocytic myeloid-derived suppressor cells (G-MDSCs) abundantly accumulate within the peripheral lymphoid compartments and target organs of mice with experimental autoimmune encephalomyelitis prior to disease remission. In vivo transfer of G-MDSCs ameliorated experimental autoimmune encephalomyelitis, significantly decreased demyelination, and delayed disease onset through inhibition of encephalitogenic Th1 and Th17 immune responses. Exposure of G-MDSCs to the autoimmune milieu led to up-regulation of the programmed death 1 ligand that was required for the G-MDSC-mediated suppressive function both in vitro and in vivo. Importantly, myeloid-derived suppressor cells were enriched in the periphery of subjects with active multiple sclerosis and suppressed the activation and proliferation of autologous CD4(+) T cells ex vivo. Collectively, this study revealed a pivotal role for myeloid-derived suppressor cells in the regulation of multiple sclerosis, which could be exploited for therapeutic purposes.