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Effects--Ethanol--Dendritic Smooth Endoplasmic Reticulum

作用--乙醇--树突状光滑内质网

基本信息

批准号：
6623542
负责人：
CYNTHIA A DLUGOS
金额：
$ 7.84万
依托单位：
STATE UNIVERSITY OF NEW YORK AT BUFFALO
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2005-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6623542
关键词：
alcoholic beverage consumption alcoholism /alcohol abuse animal old age blood tests cellular pathology cerebellar Purkinje cell cerebellar cortex dendrites endoplasmic reticulum ethanol gender difference granule cell juvenile animal laboratory rat neuropharmacology neurotoxicology transmission electron microscopy

项目摘要

Further understanding of ethanol-related effects of the Pukinje neuron (PN), the sole output neuron of the cerebellar cortex, is essential due to the deleterious effects of alcohol on balance and motor coordination. Lengthy periods of ethanol consumption result in dendritic regression and dilatation of the dendritic smooth endoplasmic reticulum (SER) within the extensive dendritic arbor of PN. The SER within PN dendrites stores calcium ions, a function that may be upset by ethanol-related imbalances. Ethanol-related SER dilatation in PN dendrites, moreover, may predict and contribute to the ethanol-related dendritic regression that has been repeatedly observed in old rats. The first aim of this proposal is to characterize the development of SER dilation in PN dendrites at several time points during a lengthy period of ethanol consumption. This will relate the time when ethanol-related SER dilatation occurs to the time when PN dendritic regression has been reported. The second aim is to confirm and characterize ethanol-related SER dilatation in parallel fibers, the axons of granule neurons (GN). Parallel fibers provide a major synaptic input to the PN and a causal relationship may exist between ethanol-related SER dilatation in the presynaptic parallel fiber and the postsynaptic PN dendrite. SER dilatation is most probably a marker of neuronal imbalances that could severely impact on cerebellar output. One hundred and twenty old male F344 and 30 old female F3244 rats will be assigned to three treatment groups (50 rats/group). Treatment groups will include a chow control group, a pair-fed group, and an ethanol group. Ten males from each treatment group will be treated for a 5,10,20 or 40 week period, respectively. Length of treatment for the female rats will be determined by the time point at which SER dilatation reached significant levels in both PN dendrites and parallel fibers. Following treatment, rats will be euthanized, the cerebella removed and prepared for transmission electron microscopy (TEM). Image analysis of scanned TEM negative will be used to quantitative the maximum and minimum diameters of SER profiles in PN dendritic branches, branch points, and spines, and in parallel fibers.

由于酒精对平衡和运动协调的有害影响，进一步了解小脑皮质唯一的输出神经元Pukinje神经元(PN)与酒精相关的影响是至关重要的。长时间的酒精摄入会导致PN广泛的树突枝内的树突状滑面内质网(SER)的树突状退缩和扩张。PN树突内的SER存储钙离子，这一功能可能会被乙醇相关的失衡所扰乱。此外，PN树突中与酒精相关的SER扩张可能预测并有助于在老年大鼠中反复观察到的与酒精相关的树突退化。这一建议的第一个目的是描述长期酒精消费期间在几个时间点上PN树突中SER扩张的发展情况。这将与酒精相关的SER扩张发生的时间和PN树突状退行性变的时间相关联。第二个目的是确认和表征酒精引起的平行纤维的SER扩张，即颗粒神经元(GN)的轴突。平行纤维为PN提供了主要的突触输入，突触前平行纤维中乙醇引起的SER扩张与突触后PN树突之间可能存在因果关系。Ser扩张很可能是神经元失衡的标志，这可能会严重影响小脑输出。将120只老年雄性F344和30只老年雌性F3244大鼠随机分为3组，每组50只。试验组将包括饲料对照组、配对饲料组和乙醇组。每组10名男性将分别接受为期5周、10周、20周或40周的治疗。雌性大鼠的治疗时间将取决于SER扩张在PN树突和平行纤维中达到显着水平的时间点。治疗后，大鼠将被安乐死，取出小脑，并准备进行透射电子显微镜(TEM)检查。扫描的透射电子显微镜底片的图像分析将被用来定量PN树枝、分支点和脊椎以及平行纤维中SER轮廓的最大和最小直径。