Does ethanol-induced lipid metabolism dysfunction aggravate symptoms of dementia?

乙醇已被证明在正常组织包括神经组织中诱导细胞凋亡。它还报告说，乙醇有一个方面，加重痴呆症的症状。我们前期的研究表明，某些腺苷酸环化酶的数量减少与酒精依赖和阿尔茨海默病的特征有关，表明cAMP介导的信号转导在这些脑中是紊乱的。本研究检测了乙醇诱导的细胞毒性和CREB重要靶基因之一的脑源性神经营养因子（BDNF）的定量变化。用SH-SY 5 Y细胞，发现乙醇暴露可降低培养细胞中BDNF的含量，而增加NF κ-B的活性。接下来，我们研究了乙醇对原代培养的大鼠皮层神经元存活和神经干细胞（NSCs）分化的影响。乙醇暴露减少神经元的存活。两个ins 关于我们 胰岛素样生长因子-1（IGF-1）和脑源性神经营养因子（BDNF）以剂量依赖方式促进神经干细胞向神经元分化，IGF-1和BDNF可抑制乙醇对神经干细胞分化的抑制作用。乙醇可能通过改变与神经营养因子相关的细胞通路来抑制神经干细胞的分化。此外，apoE对乙醇诱导的细胞毒性的异构体特异性效应被鉴定。结果表明，apoE 4的加入降低了乙醇诱导的细胞毒性，而apoE 2和apoE 3的存在都抑制了乙醇暴露的细胞毒性。apoE促进乙醇诱导的细胞损伤的确切机制尚未阐明，需要进一步的研究。然而，本研究表明，乙醇诱导的受体以下第二信使的改变通过基因和细胞内蛋白质的表达影响细胞内转因子和神经网络的改变结构，有助于认知障碍的发展。相反，诱导分化为神经元，恢复神经元数量和促进神经网络重塑可用于治疗酒精中毒和阿尔茨海默病。将这些疾病视为由脂质代谢和神经网络系统功能障碍引起的认知障碍，似乎可以拓宽治疗策略的选择。少

Ethanol has been shown to induce apoptosis in normal tissues including neural tissues. It has also reported that ethanol has an aspect of aggravate symptoms of dementia. Our previous studies suggest that the quantitative reduction of certain type of adenylyl cyclase is related to the features of alcohol dependence and Alzheimer's disease indicating that cAMP-mediated signal transduction is disordered in those brains. In the present study, we measured the ethanol-induced cytotoxicity and the quantitative alteration of brain-derived neurotrophic factor(BDNF), which is one of the important target genes of CREB. Using SH-SY5Y cells, it was revealed that the amount of BDNF was decreased by the exposure to ethanol in the cultured cells, whereas the activity of NF κ-B was increased. We next investigated the effects of ethanol on the survival on primary cultured rat cortical neurons and the differentiation of neural stem cells(NSCs). Ethanol exposure decreased the survival of neurons. Both ins … More ulin-like growth factor-1(IGF-1) and BDNF promoted neuronal differentiation of NSCs in a dose-dependent-manner, and the inhibition of NSC differentiation by ethanol was suppressed by IGF-1 and BDNF. Ethanol may inhibit NSC differentiation through alteration of cellular pathways related to neurotrophic factors. Furthermore, the isoform specific effects of apoE on the ethanol-induced cytotoxicity were identified. It was shown that the addition of apoE4 diminish the ethanol-induced cytotoxicity, whereas the presence of neither apoE2 nor apoE3 inhibits the cytotoxicity by the exposure of ethanol. The precise mechanisms of promoting effect of apoE on ethanol-induced cell damage have yet to be clarified and further investigations will be required. However, the present study suggests that the ethanol-induced alterations of second messengers below receptors effect on intracellular transfactors and alternate structure of neural network through expression of genes and intracellular proteins, contributing to the development of cognitive disturbances. To the contrary, induction of differentiation into neurons, recovery of number of neurons and promotion of remodeling of neural network may be applied to the treatment of alcoholism and Alzheimer's disease. It seems possible to broaden our choices of therapeutic strategies by approaching to those illnesses regarding them as a cognitive disorders caused by dysfunctions of lipid metabolism and neural network system. Less