Gene Expression in Long-Term Memory

长期记忆中的基因表达

• 批准号: 10311040
• 负责人: CRISTINA M ALBERINI
• 金额: $ 63.26万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10311040
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Animal Model; Area; Autophagocytosis; Biological; Brain; Cell physiology; Cognition Disorders; Disease; Gene Expression; Goals; Impaired cognition; Injury; Insulin-Like Growth Factor II; Investigation; Knowledge; Lead; Learning; Mediating; Memory; Memory Loss; Memory impairment; Mental Health; Mental Retardation; Modeling; Molecular; Mus; Nootropic Agents; Physiological; Rattus; Regulation; Research; Role; Somatomedins; Stress; Synaptic plasticity; System; Training; autism spectrum disorder; cognitive function; developmental disease; experience; long term memory; memory consolidation; mild cognitive impairment; mouse model; myelination; novel; prevent

Maintaining and promoting healthy cognitive functions, of which memory is a most important one, is one of the major goals of mental health research. Diseases, stress, injury and aging can lead to cognitive and memory impairments. It is estimated that up to one third of adults will experience a gradual decline in cognitive function known as mild cognitive impairment as they age. Furthermore, a number of diseases such as Alzheimer's disease, autism, mental retardation are associated with memory impairments. Thus, minimizing or preventing cognitive and memory impairments is a very important goal in mental health. A principal approach toward this goal is to understand the physiological mechanisms of memory formation, persistence and storage and identify molecular mechanisms and targets that can be used to enhance memory, not only for potentiating normal functions but also for developing strategies that may prevent or reverse memory loss. Using rat and mouse models, we have identified the growth factor insulin like growth factor 2 (IGF-2) as a potent memory and cognitive enhancer in healthy conditions. Using models of memory impairment in both developmental disorders and aging we found that IGF-2 significantly reverses memory losses. Our studies of the last 5 years also started elucidating some of the action mechanisms by which IGF-2 promotes memory enhancement and reverse memory deficits. One of these mechanisms emerged as the autophagy/lysosomal degradation system, a key regulator of cell functions. Furthermore, investigations of mechanisms of memory formation and enhancement in cortical regions provided evidence for slow-developing learning-induced changes distinct from the known synaptic plasticity. This proposal aims at continuing these mechanistic investigations in order to: 1- Determine the role of autophagy/lysosomal degradation in memory consolidation and IGF-2-mediated memory enhancement, as well as their critical target mechanisms; 2- Determine identity and regulation of novel biological mechanisms occurring in cortical areas following training that are critical for memory consolidation and enhancement; and 3- Determine the role of myelination in long-term memory formation. Results from these studies should significantly advance our knowledge of brain plasticity mechanisms, which may be targeted to achieve memory enhancement and to treat cognitive disorders.

维持和促进健康的认知功能，其中最重要的是 心理健康研究的主要目标之一。 疾病，压力，伤害和衰老会导致 认知和记忆力障碍。据估计，多达三分之一的成年人会经历 随着年龄的增长，认知功能的逐渐下降被称为轻度认知障碍。 此外， 许多疾病，例如阿尔茨海默氏病，自闭症，智力低下 记忆障碍。因此，最大程度地减少或预防认知和记忆障碍是非常 心理健康的重要目标。 实现此目标的主要方法是了解 记忆形成，持久性和存储的生理机制，并识别分子 可用于增强记忆的机制和目标，不仅用于增强正常状态 功能，还用于制定可能阻止或逆转记忆力损失的策略。使用老鼠和 小鼠模型，我们已经确定生长因子胰岛素（例如生长因子2（IGF-2））是有效的 在健康条件下的记忆和认知增强子。在两者中都使用记忆障碍的模型 发育障碍和衰老，我们发现IGF-2显着逆转记忆损失。我们的 过去5年的研究还开始阐明IGF-2的某些动作机制 促进内存增强和反向内存不足。这些机制之一出现为 自噬/溶酶体降解系统，细胞功能的关键调节剂。此外， 对所提供的皮质区域的记忆形成和增强机制的调查 缓慢发展学习引起的变化的证据与已知的突触可塑性不同。 该建议旨在继续进行这些机械调查，以：1-确定 自噬/溶酶体降解在记忆巩固和IGF-2介导的内存中的作用 增强及其关键目标机制； 2-确定身份和调节 训练后的皮质区域中发生的新型生物学机制至关重要 记忆合并和增强； 3-确定髓鞘形成在长期记忆中的作用 形成。这些研究的结果应大大提高我们对大脑的了解 可塑性机制，可以针对实现记忆增强和治疗认知障碍。

项目成果

Recovery of memory from infantile amnesia is developmentally constrained.

• DOI: 10.1101/lm.052621.120
• 发表时间: 2021-09
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Bisaz R;Bessières B;Miranda JM;Travaglia A;Alberini CM
• 通讯作者: Alberini CM

The neurotrophin-inducible gene Vgf regulates hippocampal function and behavior through a brain-derived neurotrophic factor-dependent mechanism.

• DOI: 10.1523/jneurosci.3145-08.2008
• 发表时间: 2008-09-24
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Bozdagi O;Rich E;Tronel S;Sadahiro M;Patterson K;Shapiro ML;Alberini CM;Huntley GW;Salton SR
• 通讯作者: Salton SR

Glucocorticoid receptors recruit the CaMKIIα-BDNF-CREB pathways to mediate memory consolidation.

• DOI: 10.1038/nn.3266
• 发表时间: 2012-12
• 期刊: NATURE NEUROSCIENCE
• 影响因子: 25
• 作者: Chen, Dillon Y.;Bambah-Mukku, Dhananjay;Pollonini, Gabriella;Alberini, Cristina M.
• 通讯作者: Alberini, Cristina M.

Introduction to the special issue on the ontogeny of hippocampal functions.

• DOI: 10.1002/hipo.23406
• 发表时间: 2022-03
• 期刊: HIPPOCAMPUS
• 影响因子: 3.5
• 作者: Ohana, Ora;Alberini, Cristina M.;Donato, Flavio
• 通讯作者: Donato, Flavio

The effect of insulin and insulin-like growth factors on hippocampus- and amygdala-dependent long-term memory formation.

• DOI: 10.1101/lm.029348.112
• 发表时间: 2014-10
• 期刊: Learning & memory (Cold Spring Harbor, N.Y.)
• 作者: Stern SA;Chen DY;Alberini CM
• 通讯作者: Alberini CM