Neurocognitive Consequences of Intermittent Hypoxia

间歇性缺氧的神经认知后果

• 批准号: 10617868
• 负责人: Alfredo J Garcia
• 金额: $ 5.54万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10617868
• 关键词: Ablation; Adult; Affect; American; Animals; Area; Attention; Behavior; Behavioral Assay; Biological Assay; Blood; Brain; Breathing; Cardiovascular Diseases; Carotid Body; Chronic; Clinical; Cognition; Cognitive; Cognitive deficits; Coupled; Data; Denervation; Development; Electrophysiology (science); Enzymes; Exposure to; Foundations; Functional disorder; Generations; Genetic; Genetic Transcription; Glutamates; Goals; Health; Hippocampus (Brain); Hypoxia; Hypoxia Inducible Factor; Impaired cognition; Impairment; In Vitro; Injury; Lead; Learning; Link; Long-Term Potentiation; Measures; Mechanics; Mediating; Memory; Memory impairment; Modeling; Molecular; Mus; Neurocognitive; Neurons; Organ; Outcome; Oxidative Stress; Parahippocampal Gyrus; Pathway interactions; Pattern; Periodicity; Peripheral; Physiology; Process; Property; Quality of life; Reactive Oxygen Species; Respiration Disorders; Risk; Rodent Model; Role; Self-Help Devices; Severities; Signal Transduction; Sleep; Sleep Apnea Syndromes; Slice; Structure; Synapses; Testing; Transcription Coactivator; Work; adult neurogenesis; animal data; base; cognitive change; cognitive function; cognitive performance; dentate gyrus; effective therapy; human imaging; hypoxia inducible factor 1; imaging study; indexing; insight; memory recognition; neurogenesis; neuroimaging; neurophysiology; positive airway pressure; prevent; relating to nervous system; respiratory; sensor; spatial memory; standard care; stem cell fate; stroke risk

PROJECT SUMMARY Sleep apnea is a respiratory disorder that causes chronic intermittent hypoxia throughout the sleep cycle. Neuroimaging studies indicate that the hippocampus is particularly vulnerable to injury in sleep apnea. In addition to the involvement of this brain structure with spatial and recognition memory, hippocampal activity is coupled to and exerts influence on peripheral chemoreflexes and respiratory patterns. Thus, along with its cognitive effects, the neurophysiological changes in the hippocampus may contribute to the development of cardiovascular disease, the increased risk for stroke that occur with untreated sleep apnea. As the duration of untreated sleep apnea persists, the severity of the condition increases, as does the risk of developing increasingly significant cognitive deficit. We hypothesize that chronic intermittent hypoxia caused by sleep apnea triggers reactive oxygen species signaling, resulting in duration-dependent changes to hippocampal neurophysiology and, in turn, causing progressive degradation in hippocampal-based cognition. We test this hypothesis in a rodent model of sleep apnea in which animals are exposed to different durations of chronic intermittent hypoxia. We examine the resulting effects on hippocampal neurophysiology and neurogenesis, focusing on principal neurons involved in learning and memory pathways. In addition to dissecting the role of reactive oxygen species signaling in cognitive changes, we explore the mechanistic origin of this signaling and the potential interaction between cardio-respiratory organs (i.e., carotid bodies) and the hippocampus. The mechanistic insights gained from this work will inform the development of more effective therapies to prevent, or fully reverse, cognitive decline in a condition that affects the quality of life for many Americans.

项目总结

项目成果

A consequence of immature breathing induces persistent changes in hippocampal synaptic plasticity and behavior: a role of prooxidant state and NMDA receptor imbalance.

未成熟呼吸的结果引起了海马突触可塑性和行为的持续变化：促氧化剂状态和NMDA受体失衡的作用。

• DOI: 10.3389/fnmol.2023.1192833
• 发表时间: 2023
• 期刊: FRONTIERS IN MOLECULAR NEUROSCIENCE
• 影响因子: 4.8
• 作者: Arias-Cavieres, Alejandra;Garcia III, Alfredo J. J.
• 通讯作者: Garcia III, Alfredo J. J.

Machine learning-based data analytic approaches for evaluating post-natal mouse respiratory physiological evolution.

• DOI: 10.1016/j.resp.2020.103558
• 发表时间: 2021-01
• 期刊: Respiratory physiology & neurobiology
• 影响因子: 2.3
• 作者: Wang W;Alzate-Correa D;Alves MJ;Jones M;Garcia AJ 3rd;Zhao J;Czeisler CM;Otero JJ
• 通讯作者: Otero JJ

Gasotransmitter modulation of hypoglossal motoneuron activity.

• DOI: 10.7554/elife.81978
• 发表时间: 2023-01-19
• 期刊: eLife
• 影响因子: 7.7
• 作者: Browe BM;Peng YJ;Nanduri J;Prabhakar NR;Garcia AJ 3rd
• 通讯作者: Garcia AJ 3rd

Finding inspiration in opioid-induced respiratory depression.

在阿片类药物引起的呼吸抑制中寻找灵感。

• DOI: 10.1113/jp279083
• 发表时间: 2020
• 期刊: The Journal of physiology
• 作者: Garcia3rd,AlfredoJ;Szujewski,CarolineC
• 通讯作者: Szujewski,CarolineC

Stage-dependent effects of intermittent hypoxia influence the outcome of hippocampal adult neurogenesis.

• DOI: 10.1038/s41598-021-85357-5
• 发表时间: 2021-03-16
• 期刊: Scientific reports
• 影响因子: 4.6
• 作者: Khuu MA;Nallamothu T;Castro-Rivera CI;Arias-Cavieres A;Szujewski CC;Garcia Iii AJ
• 通讯作者: Garcia Iii AJ