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Adenosine Kinase Expression Modulates Expression of Myelin Proteolipid Protein 腺苷激酶的表达调节髓磷脂蛋白的表达
Pub Date : 2007-12-07 DOI: 10.2174/1874082000701010015
N. Wu, D. Boison
Adenosine is known to regulate myelination in vitro. Here we tested the hypothesis that adenosine, regulated by adenosine kinase (ADK), might regulate myelin-specific protein expression and myelination in vivo. We demonstrate that transgenic overexpression of ADK, which reduces adenosine in mouse brain, results in increased levels of myelin prote- olipid protein.
已知腺苷在体外调节髓鞘形成。在这里,我们验证了腺苷受腺苷激酶(ADK)调节的假设,腺苷可能调节髓鞘特异性蛋白的表达和体内髓鞘形成。我们证明转基因过表达的ADK,减少了小鼠脑中的腺苷,导致髓磷脂蛋白-脂质蛋白水平升高。
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引用次数: 3
Cell Growth in Response to Mechanical Stiffness is Affected by Neuron- Astroglia Interactions 神经元-星形胶质细胞相互作用影响细胞生长对机械刚度的响应
Pub Date : 2007-11-15 DOI: 10.2174/1874082000701010007
Xue Jiang, Penelope C. Georges, Baogang Li, Y. Du, Melinda K. Kutzing, M. Previtera, N. Langrana, B. Firestein
Cell adhesion and morphology are affected by the mechanical properties of the extracellular matrix. Using polyacrylamide gels as cell substrates, the cellular response to substrate compliance was investigated in pure neuronal, pure astroglial, or mixed co-cultures. Substrates used spanned a large range of stiffnesses including that of brain tissue. In both pure and mixed cultures, immature (vimentin+) astroglia adhered best to stiffest gels. Mature (GFAP+) astrocyte ad- hesion peaked on intermediate stiffness, while pure GFAP+ astroglial adhesion displayed no intermediate preference and increased with stiffness. Neurite length was constant with stiffness; however, primary dendrite number was lowest on in- termediate gels. Pure neuronal cultures were more adherent to hard gels, while mixed cultures had no stiffness preference. Furthermore, we investigated the role of stiffness in the modulation of the neurotoxic effect of glutamate. Exposure to two glutamate concentrations (500 and 1000 � M) of cultured spinal cord neurons induced cell death. The damage elicited by 500 � m glutamate to neurons in a mixed culture of spinal cord cells is most severe on soft 300 Pa gels. The neurotoxic ef- fect of glutamate on neurons cultured on hard gels where astrocytes are present was strongly attenuated compared with that observed on soft gels, where there is a relatively low number of astrocytes. Our data suggest that mechanical stiffness of the substrate affects the response of both neurons and astroglia, and this response is varied by interaction between the two cell types.
细胞外基质的力学性能影响细胞的粘附和形态。使用聚丙烯酰胺凝胶作为细胞底物,在纯神经元、纯星形胶质或混合共培养中研究了细胞对底物依从性的反应。所使用的基质跨越了很大的刚度范围,包括脑组织的刚度。在纯培养和混合培养中,未成熟的(vimentin+)星形胶质细胞粘附在最硬的凝胶上效果最好。成熟(GFAP+)星形胶质细胞黏附在中等硬度时达到峰值,而纯GFAP+星形胶质细胞黏附没有中间偏好,并随着硬度的增加而增加。神经突长度随刚度不变;而初生枝晶数量在中间凝胶中最少。纯神经元培养物对硬凝胶的粘附性更强,而混合培养物对硬度没有偏好。此外,我们研究了僵硬在谷氨酸的神经毒性作用的调节中的作用。暴露于两种谷氨酸浓度(500和1000 μ M)的培养脊髓神经元诱导细胞死亡。500 μ m谷氨酸对脊髓细胞混合培养中神经元的损伤在300 Pa软凝胶中最为严重。谷氨酸对存在星形胶质细胞的硬凝胶培养的神经元的神经毒性作用,与在星形胶质细胞数量相对较少的软凝胶上观察到的神经毒性作用相比,明显减弱。我们的数据表明,基质的机械刚度影响神经元和星形胶质细胞的反应,这种反应因两种细胞类型之间的相互作用而变化。
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引用次数: 38
A Tale of Two Hormones: Role of Leptin and Insulin in Hippocampal Synaptic Function 两种激素的故事:瘦素和胰岛素在海马突触功能中的作用
Pub Date : 2007-10-29 DOI: 10.2174/1874082000701010001
J. Harvey
It is well documented that the endocrine hormones, leptin and insulin provide signals to specific hypothalamic brain regions to regulate energy balance. However, the past decade of research has not only revealed the widespread ex- pression of insulin and leptin receptors in the CNS, but has also identified numerous additional functions of these hor- mones in the brain. In particular, there is growing evidence that these hormones markedly influence hippocampal excita- tory synaptic transmission as well as hippocampal synaptic plasticity. More recent studies have also identified links be- tween dysregulation of leptin and insulin systems and the development of neurodegenerative disorders such as Alz- heimer's disease. Here we review the recent evidence supporting a role for these hormones in modulating hippocampal synaptic function in health and disease.
有充分的证据表明,内分泌激素、瘦素和胰岛素向大脑下丘脑的特定区域提供信号来调节能量平衡。然而,过去十年的研究不仅揭示了胰岛素和瘦素受体在中枢神经系统中的广泛表达,而且还发现了这些激素在大脑中的许多其他功能。特别是,越来越多的证据表明,这些激素显著影响海马兴奋性突触传递以及海马突触可塑性。最近的研究也发现了瘦素和胰岛素系统失调与阿尔茨海默病等神经退行性疾病的发展之间的联系。在这里,我们回顾了最近的证据支持这些激素在调节海马突触功能在健康和疾病中的作用。
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引用次数: 0
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