自噬增强剂以减少睡眠障碍 (SpSleep)
自噬增强剂减少睡眠障碍：一种综合方法
这项临床试验研究亚精胺补充剂对患有轻度认知障碍（MCI）的老年人睡眠质量和记忆功能的影响。MCI是一种与痴呆症风险增加相关的病症，特别是在因阿尔茨海默病导致的MCI患者中。睡眠障碍已被确定为导致认知能力下降的可改变因素，针对睡眠结构的干预措施可能具有预防或减缓这种下降的治疗潜力。
亚精胺是一种天然存在的多胺，存在于小麦胚芽和大豆等食物中。它能诱导自噬，这是一种对神经元维持和功能至关重要的细胞降解和回收过程。在动物研究中，亚精胺已被证明可以改善记忆表现、减少神经炎症并支持线粒体健康。针对主观认知下降或MCI患者的人体试验初步结果表明，亚精胺可能具有认知益处，但结果并非明确，且对睡眠的影响尚未得到系统评估。
在这项随机、双盲、安慰剂对照试验中，76名年龄在55至70岁之间患有MCI的参与者将接受亚精胺（6毫克/天）或安慰剂治疗12周。睡眠将通过夜间脑电图在受控实验室环境中进行评估，重点关注慢波睡眠和睡眠纺锤波活动等指标。记忆表现将在干预前后使用标准化的神经心理学测试进行评估。数值技能仅在基线时测试，以将MCI患者与健康对照组进行比较。
将收集血样以量化代谢指标、神经退行性疾病相关生物标志物和自噬相关蛋白。一个由38名认知健康个体组成的对照组将接受类似的睡眠和认知评估，但不接受任何补充剂。
本研究的主要目标是描述亚精胺对睡眠依赖性记忆巩固的影响，并识别与衰老和神经退行性疾病相关的生物变化。结果可能为制定旨在保护痴呆症风险人群认知功能的非药物策略提供信息。
研究概览
详细说明
轻度认知障碍（MCI）是一种临床病症，其特征是可测量的认知能力下降超出与年龄相关的正常范围，但尚未达到痴呆标准，通常由阿尔茨海默病（AD）引起。 该病症与进展为AD或其他形式痴呆的风险增加相关。 睡眠结构紊乱日益被认为是神经退行性疾病病理生理学中的一个因素，针对睡眠相关机制的早期干预可能有助于延缓进一步的认知衰退。 本临床试验评估了精胺补充剂对诊断为MCI的老年人睡眠质量和睡眠依赖性记忆巩固的影响。
经过一个适应夜和基于整夜脑电图（EEG）的初始基线睡眠评估后，参与者将被随机分配到精胺组或安慰剂组。 干预措施包括每日口服6毫克精胺（以三包2毫克小袋装形式给药），持续12周。 试验采用随机、双盲、安慰剂对照设计。 外观和味道相同的安慰剂小袋仅含有微晶纤维素。 在12周的补充期后，参与者将返回进行第二次整夜脑电图评估。
一个健康对照组（n=38），年龄和性别匹配，将接受类似的基线评估，但不接受任何干预。 这些数据将为睡眠和认知参数提供规范性参考值。
研究的主要目的是评估精胺对睡眠结构的影响，通过整夜多导睡眠图测量，特别关注慢波睡眠和睡眠纺锤波活动，这些是与睡眠依赖性记忆巩固相关的脑电图标志物，已知随年龄和神经退行性变而下降。 次要结果包括记忆巩固的变化（通过一系列针对陈述性、程序性和视觉空间记忆领域的认知任务评估），以及数字技能（通过例如数字-字母决策任务、柏林数字能力测试进行测试）。 测试在每次脑电图夜前后进行，以评估整夜巩固效应。 所有参与者将在两次脑电图夜前佩戴活动记录仪，以监测睡眠-觉醒周期和身体活动。
额外的生物学终点将检查循环神经肽、胰岛素-葡萄糖稳态和自噬相关生物标志物的变化。 每次脑电图会话和补充开始后两周收集血液样本。 生理评估包括口服葡萄糖耐量试验、炎症标志物（例如白细胞介素（IL）-6、肿瘤坏死因子（TNF-α））、神经保护因子（例如神经肽Y、真核翻译起始因子5A（eIF5A）的羟腐胺修饰）和代谢指标（例如空腹胰岛素、葡萄糖和血脂谱）的测量。
参与者将使用3特斯拉磁共振成像扫描仪进行脑部结构成像，以排除患有共病神经疾病（例如既往中风、其他神经退行性疾病）的个体，并评估脑部形态。 通过标准化的预筛查程序，包括临床访谈和神经心理学评估，确定参与者的资格。
研究包括76名年龄在55-70岁之间的MCI参与者，随机分配到精胺组或安慰剂组（每组n=38）。 基于先前的初步发现和预期的流失率，样本量提供了足够的统计功效来检测中等到大的效应大小。
本研究旨在调查精胺补充对早期认知衰退个体神经生理学和认知结果的影响。 预计结果将有助于不断增长的证据体系，评估精胺作为一种安全的、基于营养的策略，在衰老背景下维持大脑健康和认知功能。
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Agnes Flöel, Prof. Dr.
- 电话号码：+49 (0)3834 86-6815
- 邮箱：agnes.floeel@med.uni-greifswald.de
研究联系人备份
- 姓名：Silke M Wortha, Dr.
- 电话号码：+49 3834 86 - 6704
- 邮箱：SilkeMaria.Wortha@med.uni-greifswald.de
学习地点
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Mecklenburg-Vorpommern
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Greifswald、Mecklenburg-Vorpommern、德国、17475
- 招聘中
- Department of Neurology, University Medicine Greifswald
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接触：
- Agnes Flöel, Prof. Dr.
- 电话号码：+49 (0)3834 86-6815
- 邮箱：agnes.floeel@med.uni-greifswald.de
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
纳入标准（MCI患者）：
- 男性和女性
- 签署书面同意参与研究
- 德语为母语水平
- 年龄在55至70岁之间
轻度认知障碍（MCI）操作化定义为：
- 患者、亲属或临床工作人员报告的认知能力变化（即历史或观察到的随时间恶化证据）
- 记忆障碍的客观证据（韦氏逻辑记忆量表（WMS-LM）至少低于正常范围1.0个标准差）；其他认知领域也可能受影响（即遗忘型MCI和遗忘型+MCI）
- 功能能力的独立性得以保留
- 无痴呆
排除标准（MCI患者）：
- 无法提供知情同意的患者
- 通过膳食补充剂摄入多胺和/或参与相应干预研究
- 根据《精神障碍诊断与统计手册》第4版（DSM-IV）诊断为痴呆
- 任何影响临床或神经心理学检查程序的情况
- 糖尿病
- 多囊卵巢综合征
- 癫痫迹象、局灶性脑损伤或头部外伤伴意识丧失或伤后立即意识模糊
- 既往卒中史
- 严重未治疗的医疗问题或不稳定的医疗状况
- 当前重度抑郁发作
- 精神障碍
- 双相情感障碍
- 当前或既往物质滥用
- 其他神经退行性疾病，例如帕金森病
- 血管性痴呆
- 酒精滥用
- 过去3个月内及整个研究期间参与干预性研究
- 睡眠障碍
- 服用主要影响中枢神经系统的药物（例如抗精神病药、抗抑郁药、苯二氮䓬类药物或任何类型的非处方助眠药物如缬草；抗痴呆药物）
- 已知对小麦胚芽、麸质或组胺不耐受或过敏
纳入标准（健康对照）：
- 男性和女性
- 签署书面同意参与研究
- 德语为母语水平
- 年龄在55至70岁之间
- 否认主观认知障碍
排除标准（健康对照）：
- 无法提供知情同意的受试者
- 通过膳食补充剂摄入多胺和/或参与相应干预研究
- 根据《精神障碍诊断与统计手册》第4版（DSM-IV）诊断为痴呆
- 轻度认知障碍（MCI），定义如上文患者纳入标准所述
- 任何干扰临床或神经心理学检查程序的情况
- 糖尿病
- 多囊卵巢综合征
- 癫痫迹象、局灶性脑损伤或头部外伤伴意识丧失或伤后立即意识模糊
- 既往卒中史
- 严重未治疗的医疗问题或不稳定的医疗状况
- 当前重度抑郁发作
- 精神障碍
- 双相情感障碍
- 当前或既往物质滥用
- 其他神经退行性疾病，例如帕金森病
- 血管性痴呆
- 酒精滥用
- 过去3个月内及整个研究期间参与干预性研究
- 睡眠障碍
- 服用主要影响中枢神经系统的药物（例如抗精神病药、抗抑郁药、苯二氮䓬类药物或任何类型的非处方助眠药物如缬草；抗痴呆药物）
学习计划
研究是如何设计的？
设计细节
- 主要用途：基础科学
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：膳食补充剂
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每日分3次补充6毫克亚精胺
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无干预：健康老年对照组
基线比较，健康对照组不属于干预部分
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安慰剂比较：饮食安慰剂
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每日分3次补充6毫克安慰剂（安慰剂由麦芽糊精、米提取物微晶纤维素混合物、无水柠檬酸、沉淀二氧化硅（E551）组成）
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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亚精胺补充剂对脑电图（EEG）平均功率谱测量的睡眠质量的影响
大体时间：基线、12周随访
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计算个体平均功率谱。 随后，在以下脑电图频段计算平均功率：慢振荡（0.5-1 Hz）、低δ波（1-1.5 Hz）、δ波（1-4 Hz）、θ波（4-8 Hz）和β波（15-25 Hz）。 对于亚精胺效应，将基线和随访的脑电图数据进行比较。 |
基线、12周随访
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通过脑电图评估的睡眠纺锤波计数测量的亚精胺补充对睡眠质量的影响
大体时间：基线，12周随访
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计算个体平均功率谱。 随后，在以下EEG频段中计算平均功率：慢速前额纺锤波（8-12 Hz）、快速顶叶纺锤波（12-15 Hz），并统计慢速前额和快速顶叶离散纺锤波的数量。 基于先前研究中采用的算法进行纺锤波检测。 对于亚精胺效应，将基线和随访的EEG数据相互比较。 |
基线，12周随访
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通过脑电图评估睡眠纺锤波功率测量的亚精胺补充对睡眠质量的影响
大体时间：基线, 12周随访
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计算个体平均功率谱。随后，在以下EEG频带中计算平均功率：慢波前额纺锤波（8-12 Hz）、快波顶叶纺锤波（12-15 Hz）。纺锤波功率作为纺锤波活动的进一步测量指标进行分析。纺锤波检测基于先前研究采用的算法进行。 对于亚精胺效应，将基线和随访期的EEG数据相互比较。 |
基线, 12周随访
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Effects of spermidine supplementation on sleep-related alertness as measured by computer-based task
大体时间：baseline, 12-week follow-up
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The alertness task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. It comprises two runs without and two runs with a prior warning tone. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other. Task performance is measured by speed (in ms) and hit/false or miss. |
baseline, 12-week follow-up
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Effects of spermidine supplementation on sleep-related visual-spatial memory as measured by computer-based task
大体时间：baseline, 12-week follow-up
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The visual-spatial memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 60 objects (e.g., photo of a band-aid) placed in front of a background (e.g., photo of a treatment room in a doctor's office), a retrieval phase follows directly after encoding in the evening before bedtime, in which 30 randomly selected images from the total of 60 are tested. Participants should memorize the position of the object placed in front of the background and select the correct position by pressing a button. In the next morning, the remaining 30 images are tested in a recall phase. Task performance is measured by speed (in ms) and hit/false or miss. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other. |
baseline, 12-week follow-up
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Effects of spermidine supplementation on sleep-related verbal memory as measured by computer-based task
大体时间：baseline, 12-week follow-up
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The verbal memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 44 word pairs, a retrieval phase follows directly after encoding in the evening before bedtime, in which all word pairs are tested in randomized order. The next morning, all word pairs are tested in a recall phase. Task performance is measured by hit/false or miss. For the spermidine effect, baseline and follow-up task performances of SCD and MCI participants are compared with each other. |
baseline, 12-week follow-up
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Differences in autophagy-related blood markers pre and post spermidine intervention in SCD and MCI as measured by polyamine concentration
大体时间：baseline, 2 weeks after baseline, 12-week follow-up
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concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
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baseline, 2 weeks after baseline, 12-week follow-up
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Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by electroencephalography (EEG) mean power spectra
大体时间：baseline data
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Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow oscillations (0.5-1 Hz), low delta (1-1.5 Hz), delta (1-4 Hz), theta (4-8 Hz), and beta (15-25 Hz). The differences between SCD / MCI and healthy controls are assessed from baseline EEG data. |
baseline data
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Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle count assessed from EEG
大体时间：baseline data
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Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz), and the number of slow frontal and fast parietal discrete spindles are counted. Spindle detection is performed based on an algorithm adopted from previous studies. The differences between SCD / MCI and healthy controls are assessed from baseline EEG data. |
baseline data
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Differences in sleep quality between SCD or MCI and healthy controls (HC) as measured by sleep spindle power assessed from EEG
大体时间：baseline data
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Individual mean power spectra are calculated. Subsequently, the mean power is calculated in the following EEG bands: slow frontal spindle (8-12 Hz), fast parietal spindle (12-15 Hz). Spindle power is analyzed as a further measure of spindle activity. Spindle detection is performed based on an algorithm adopted from previous studies. The differences between SCD / MCI and healthy controls are assessed from baseline EEG data. |
baseline data
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Differences in autophagy-related blood markers pre and post spermidine intervention in SCD or MCI as measured by eIF5A hypusination
大体时间：baseline, 2 weeks after baseline, 12-week follow-up
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assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
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baseline, 2 weeks after baseline, 12-week follow-up
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Differences in neuropeptide Y blood levels pre and post spermidine intervention in SCD or MCI
大体时间：baseline, 12-week follow-up
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Neuropeptide Y blood levels in pg/ml analyzed from serum blood sample
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baseline, 12-week follow-up
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Differences in sleep-related alertness between SCD or MCI participants and healthy controls as measured by computer-based task
大体时间：baseline
|
The alertness task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. It comprises two runs without and two runs with a prior warning tone. The differences between SCD / MCI and healthy controls are assessed from baseline task data. Task performance is measured by speed (in ms) and hit/false or miss. |
baseline
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Differences in sleep-related visual-spatial memory between SCD or MCI participants and healthy controls as measured by computer-based task
大体时间：baseline
|
The visual-spatial memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 60 objects (e.g., photo of a band-aid) placed in front of a background (e.g., photo of a treatment room in a doctor's office), a retrieval phase follows directly after encoding in the evening before bedtime, in which 30 randomly selected images from the total of 60 are tested. Participants should memorize the position of the object placed in front of the background and select the correct position by pressing a button. In the next morning, the remaining 30 images are tested in a recall phase. Task performance is measured by speed (in ms) and hit/false or miss. The differences between SCD / MCI and healthy controls are assessed from baseline task data. |
baseline
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Differences in sleep-related verbal memory between SCD or MCI participants and healthy controls as measured by computer-based task
大体时间：baseline
|
The verbal memory task is trained at adaptation night and assessed at baseline and follow-up before and after sleep. After an encoding phase consisting of 44 word pairs, a retrieval phase follows directly after encoding in the evening before bedtime, in which all word pairs are tested in randomized order. The next morning, all word pairs are tested in a recall phase. Task performance is measured by hit/false or miss. The differences between SCD / MCI and healthy controls are assessed from baseline task data. |
baseline
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Differences in neuropeptide Y blood levels between SCD or MCI and healthy controls
大体时间：baseline data
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blood levels in pg/ml analyzed from serum blood sample
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baseline data
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Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by polyamine concentration
大体时间：baseline data
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concentration in nmol / mg Protein assessed via Peripheral Blood Mononuclear Cells (PBMCs)
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baseline data
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Differences in autophagy-related blood markers between SCD or MCI and healthy controls as measured by eIF5A hypusination
大体时间：baseline data
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assessed via Hypusinated eIF5A levels (Western Blot) from Peripheral Blood Mononuclear Cells (PBMCs)
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baseline data
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Differences in numerical skills between SCD or MCI patients and healthy controls as measured by lexical decision task
大体时间：assessed at baseline only
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Participants complete a computer-based lexical decision task, in which a row of six symbols is presented after a fixation cross.
Depending on the condition, the test subjects must decide by pressing a key on the keyboard whether the row presented contains a letter (e.g., condition 1) or a digit (e.g., condition 2).
Each condition consists of two blocks.
After the first block, there is a short pause before the second block starts.
The condition (digit or letter) with which the trial starts is randomized for each test subject.
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assessed at baseline only
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Differences in numerical skills between SCD or MCI participants and healthy controls as measured by Berlin Numeracy Test
大体时间：assessed at baseline only
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The Berlin Numeracy Test contains 4 short, text-based questions testing statistical numeracy and risk literacy, requiring Bayesian inference for problems like understanding probabilities in health concerns (e.g., poisonous mushrooms) or lotteries, often presenting data in relative/absolute numbers and asking for probability estimates.
Correct answers scored for a total of 0-4 points.
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assessed at baseline only
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合作者和调查者
出版物和有用的链接
一般刊物
- Marshall L, Helgadottir H, Molle M, Born J. Boosting slow oscillations during sleep potentiates memory. Nature. 2006 Nov 30;444(7119):610-3. doi: 10.1038/nature05278. Epub 2006 Nov 5.
- Minois N, Carmona-Gutierrez D, Madeo F. Polyamines in aging and disease. Aging (Albany NY). 2011 Aug;3(8):716-32. doi: 10.18632/aging.100361.
- Gupta VK, Pech U, Bhukel A, Fulterer A, Ender A, Mauermann SF, Andlauer TF, Antwi-Adjei E, Beuschel C, Thriene K, Maglione M, Quentin C, Bushow R, Schwarzel M, Mielke T, Madeo F, Dengjel J, Fiala A, Sigrist SJ. Spermidine Suppresses Age-Associated Memory Impairment by Preventing Adverse Increase of Presynaptic Active Zone Size and Release. PLoS Biol. 2016 Sep 29;14(9):e1002563. doi: 10.1371/journal.pbio.1002563. eCollection 2016 Sep.
- Madeo F, Eisenberg T, Pietrocola F, Kroemer G. Spermidine in health and disease. Science. 2018 Jan 26;359(6374):eaan2788. doi: 10.1126/science.aan2788.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
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