BETA ADRENERGIC RECEPTORS IN ALZHEIMER'S DISEASE
BETA ADRENERGIC RECEPTORS IN ALZHEIMER'S DISEASE
批准号:
3802977
负责人:
ANAT BIEGON
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
--
资助国家:
美国
项目状态:
未结题
起止时间:
至
中文摘要
阿尔茨海默病(AD)与以下几种疾病的神经元丢失有关
大脑中的神经递质系统,包括去甲肾上腺素系统。
蓝斑神经元的丢失可能导致突触后改变
在特定区域的β肾上腺素能受体(BAR)群体中,
可能反过来促成这种疾病的表现。现在
建议研究神经解剖学分布和亚型。
死后条件下与AD相关的BAR变化的特异性。
AD的局部效应将通过体外受体来研究
阿尔茨海默病患者脑切片放射自显影与年龄、性别的关系
匹配的对照在死后获得,两者都有足够的代表性
性别。只有没有药物和神经病理的大脑才会被包括在
对照组。AD组由确诊为AD患者组成
NINCDS-ADRDA标准与基于以下诊断的确认
尸检大脑的组织病理学检查。总条数将为
使用150 PM 125I-碘吲哚进行评估。将在中检查Beta1绑定
100 nm Zinterol,一种选择性的Beta2阻滞剂和Beta2的存在
受体将在100 nm美托洛尔存在的情况下可视化。
选择性Beta1试剂。在存在的情况下测量非特定结合
普萘洛尔1000 nm。酒吧的地区性变化将与
阿尔茨海默病患者个体的各种临床特征
了解这些变化对以下领域的贡献
阿尔茨海默病患者的神经行为异常。
英文摘要
Alzheimer's disease (AD) is associated with neuronal losses in several
neurotransmitter systems, including the noradrenergic system, in the brain.
Loss of neurons in the locus coeruleus may result in postsynaptic changes
in beta adrenergic receptor (BAR) populations in specific regions, which
may in turn contribute to the manifestations of the disease. The present
proposal is designed to study the neuroanatomical distribution and subtype
specificity of changes in BAR related to AD under postmortem conditions.
The regional effects of AD will be studied by in vitro receptor
autoradiography on sections from brains of AD patients and age- and sex
matched controls obtained postmortem, with adequate representation of both
sexes. Only drug- and neuropathology-free brains will be included in the
control group. The AD group is composed of patients diagnosed using
NINCDS-ADRDA criteria with a confirmation of the diagnosis based on
histopathological examination of the brain postmortem. Total BAR will be
assessed using 150 pM 125I-iodopindolol. Beta1 binding will be examined in
the presence of 100nM Zinterol, a selective beta2 blocker, and beta2
receptors will be visualized in the presence of 100nM metoprolol, a
selective beta1 agent. Non specific binding is measured in the presence of
1000nM propranolol. Regional changes in BAR will be correlated with
various clinical features of individual AD patients in an attempt to
understand the contribution of these changes to the spectrum of
neurobehavioral abnormalities seen in AD.
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