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，其中记忆是最重要的一项

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

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

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.

Insulin-like growth factor 2 reverses memory and synaptic deficits in APP transgenic mice.

• DOI: 10.15252/emmm.201404228
• 发表时间: 2014-10
• 期刊: EMBO molecular medicine
• 影响因子: 11.1
• 作者: Pascual-Lucas M;Viana da Silva S;Di Scala M;Garcia-Barroso C;González-Aseguinolaza G;Mulle C;Alberini CM;Cuadrado-Tejedor M;Garcia-Osta A
• 通讯作者: Garcia-Osta A