Mechanisms involved in age-related memory impairment and sleep in Drosophila

果蝇年龄相关记忆障碍和睡眠的机制

• 批准号: 23500394
• 负责人: HORIUCHI Junjiro
• 金额: $ 3.33万
• 依托单位: Tokyo Metropolitan Institute of Medical Science (2013)Tokyo Metropolitan University (2011-2012)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23500394/
• 关键词: 学習; 記憶; 加齢性記憶障害; 睡眠; ショウジョウバエ; 長期記憶; 老化; シナプス可塑性

As we age, we suffer a decrease in memory. This phenomenon is known as age-related memory impairment (AMI). AMI is a serious social and medical problem, and it becomes more severe as we age. To understand the causes of AMI, we studied it in Drosophila. We found that aging causes an increase in a protein, pyruvate carboxylase (PC). PC is found in glia, cells that interact with neurons. Increasing PC activity in glia inhibits production D-serine, a neuromodulator that regulates neuronal activity. Feeding D-serine to old flies decreases AMI. This indicates that decreased glial production of the neuromodulator D-serine is a cause of AMI.In a second project, we studied sleep in Drosophila. Sleep is essential for many organisms, but its regulation is still unclear. We found that sleep is regulated by the Ca2+/calmodulin signaling pathway, a pathway known to control many biological processes. Our results suggest a mechanism through which sleep may be linked to other biological processes.

随着年龄的增长，我们的记忆力会下降。这种现象被称为与年龄相关的记忆障碍（AMI）。急性心肌梗死是一个严重的社会和医学问题，随着年龄的增长，它变得更加严重。为了了解AMI的原因，我们研究了果蝇。我们发现，衰老导致蛋白质丙酮酸羧化酶（PC）的增加。PC存在于神经胶质细胞中，这些细胞与神经元相互作用。增加神经胶质细胞中PC活性抑制D-丝氨酸的产生，D-丝氨酸是一种调节神经元活性的神经调质。给老年果蝇喂食D-丝氨酸可降低AMI。这表明神经胶质细胞分泌的神经调质D-丝氨酸的减少是AMI的一个原因。在第二个项目中，我们研究了果蝇的睡眠。睡眠对许多生物体来说是必不可少的，但其调节机制仍不清楚。我们发现睡眠是由Ca 2 +/钙调素信号通路调节的，这是一种已知控制许多生物过程的通路。我们的研究结果表明，睡眠可能与其他生物过程有关。

项目成果

Mg(2+) block of Drosophila NMDA receptors is required for long-term memory formation and CREB-dependent gene expression.

• DOI: 10.1016/j.neuron.2012.03.039
• 发表时间: 2012-06-07
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Miyashita T;Oda Y;Horiuchi J;Yin JC;Morimoto T;Saitoe M
• 通讯作者: Saitoe M

Olfactory aversive conditioning forms two distinct memory components in Drosophila

嗅觉厌恶调节在果蝇中形成两种不同的记忆成分

• 发表时间: 2014
• 作者: Naganos;S.;Ueno;K.;Horiuchi;J.;Saitoe;M
• 通讯作者: M

Long-term memory formation requires neuron-glia signaling to induce protein synthesis

长期记忆的形成需要神经元-胶质细胞信号传导来诱导蛋白质合成

• 发表时间: 2013
• 作者: Matsuno;M.;Horiuchi;J.;Saitoe;M
• 通讯作者: M

Age-related memory impairment in Drosophila is caused by an oxidative stress-independent impairment of glial neuromodulator release

果蝇年龄相关的记忆障碍是由神经胶质神经调节剂释放的氧化应激独立损伤引起的

• 发表时间: 2014
• 作者: Horiuchi;J.;Yamazaki;Y.;Saitoe;M
• 通讯作者: M

Coincident stimulation of two independent pathways triggers dopamine release which enhances synaptic transmission in Drosophila mushroom bodies

两条独立通路的同时刺激会触发多巴胺释放，从而增强果蝇蘑菇体内的突触传递

• 发表时间: 2013
• 作者: 上野耕平;堀内純二郎;齊藤実
• 通讯作者: 齊藤実