Characterizing evolutionarily conserved mechanisms underlying sleep, clocks, and memory

表征睡眠、时钟和记忆背后的进化保守机制

• 批准号: 10807806
• 负责人: JASON ROBERT GERSTNER
• 金额: $ 12.74万
• 依托单位: WASHINGTON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-13 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10807806
• 关键词: Activity Cycles; Affect; American; Behavioral Assay; Biomedical Research; Cardiovascular Diseases; Circadian Rhythms; Diabetes Mellitus; Electrophysiology (science); Genetic; Image; Learning; Link; Medical; Memory; Metabolism; Molecular; Nerve Tissue; Neuroglia; Neurons; Outcome; Phylogenetic Analysis; Physiological; Process; Rest; Site; Sleep; Sleep Deprivation; Sleep Disorders; Sleep disturbances; Synapses; Synaptic plasticity; Wakefulness; chronic pain; cognitive function; comorbidity; nervous system disorder; neural; novel

Sleep disturbance and sleep disorders affect millions of Americans and are commonly found with other existing medical conditions including cardiovascular disease, chronic pain, diabetes, and neurological disorders. To better understand the comorbidities of sleep disturbance and their negative outcomes, we need to first understand basic sleep function. Current biomedical research has not been able to adequately explain sleep function, and the subject remains controversial. Adaptive processes, such as synaptic plasticity, learning, and memory, are sensitive to sleep loss, which may provide important clues for identifying the physiological function of sleep. Cellular and molecular processes that are critical for sleep function within nervous tissue also may not be restricted to neurons, but may include glial cells, which are known to regulate metabolism, sleep, and cognitive function. Changes in neuronal-glial interactions, particularly around synapses related to activity- and energy-dependent demands during wakefulness, are therefore key sites to investigate the functional aspects of sleep. Here, we propose studies in phylogenetically diverse species that integrate the circadian rhythm of rest-activity cycles with changes in sleep need. We also provide novel avenues for tackling testable questions related to evolutionarily conserved cellular and molecular mechanisms underlying activity dependent changes in synaptic activity that are sensitive to sleep and are critical for cognitive function.

睡眠障碍和睡眠障碍影响着数百万美国人，并且在其他现有的医疗保健中也很常见。 这些疾病包括心血管疾病、慢性疼痛、糖尿病和神经系统疾病。更好地了解 睡眠障碍的合并症及其负面后果，我们需要首先了解基本的睡眠功能。 目前的生物医学研究还不能充分解释睡眠功能， 争议适应性过程，如突触可塑性、学习和记忆，对睡眠不足很敏感， 可能为识别睡眠的生理功能提供重要线索。细胞和分子过程， 对神经组织内的睡眠功能至关重要，也可能不限于神经元，而是可能包括神经胶质细胞， 已知其调节新陈代谢、睡眠和认知功能。神经元-胶质细胞相互作用的变化， 因此，在清醒状态下，特别是与活动和能量依赖需求相关的突触周围， 研究睡眠功能的网站。在这里，我们建议对遗传多样性物种进行研究， 将休息-活动周期的昼夜节律与睡眠需求的变化相结合。我们还提供了新的途径， 解决与进化上保守的细胞和分子机制相关的可测试问题 突触活动的依赖性变化，对睡眠敏感，对认知功能至关重要。

项目成果

Glitazone Treatment Rescues Phenotypic Deficits in a Fly Model of Gaucher/Parkinson's Disease.

• DOI: 10.3390/ijms222312740
• 发表时间: 2021-11-25
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Shola-Dare O;Bailess S;Flores CC;Vanderheyden WM;Gerstner JR
• 通讯作者: Gerstner JR

The transcriptional repressor Rev-erbα regulates circadian expression of the astrocyte Fabp7 mRNA.

转录抑制因子 Rev-erbα 调节星形胶质细胞 Fabp7 mRNA 的昼夜节律表达。

• DOI: 10.1016/j.crneur.2021.100009
• 发表时间: 2021
• 期刊: Current research in neurobiology
• 作者: Vanderheyden,WilliamM;Fang,Bin;Flores,CarlosC;Jager,Jennifer;Gerstner,JasonR
• 通讯作者: Gerstner,JasonR

FABP7: a glial integrator of sleep, circadian rhythms, plasticity, and metabolic function.

• DOI: 10.3389/fnsys.2023.1212213
• 发表时间: 2023
• 期刊: FRONTIERS IN SYSTEMS NEUROSCIENCE
• 影响因子: 3
• 作者: Gerstner, Jason R.;Flores, Carlos C.;Lefton, Micah;Rogers, Brooke;Davis, Christopher J.
• 通讯作者: Davis, Christopher J.

A Dichotomous Role for FABP7 in Sleep and Alzheimer's Disease Pathogenesis: A Hypothesis.

• DOI: 10.3389/fnins.2022.798994
• 发表时间: 2022
• 期刊: FRONTIERS IN NEUROSCIENCE
• 影响因子: 4.3
• 作者: Needham, Hope;Torpey, Grace;Flores, Carlos C.;Davis, Christopher J.;Vanderheyden, William M.;Gerstner, Jason R.
• 通讯作者: Gerstner, Jason R.