Effects of Prenatal Alcohol Exposure on Synaptic Plasticity and Auditory Processing

产前酒精暴露对突触可塑性和听觉处理的影响

• 批准号: 10579975
• 负责人: Padmashri Ragunathan
• 金额: $ 27.11万
• 依托单位: CREIGHTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-05 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10579975
• 关键词: AMPA Receptors; Acoustics; Affect; Agonist; Animal Model; Auditory; Auditory Brainstem Responses; Auditory Evoked Potentials; Auditory area; Autopsy; Behavior; Brain; Brain-Derived Neurotrophic Factor; Cells; Central Auditory Processing Disorder; Child; Cognitive deficits; Communities; Dendritic Spines; Development; Electrophysiology (science); Exhibits; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Fetal alcohol effects; Flavones; Goals; Hearing; Human; Impairment; Individual; Measures; Mediating; Mus; Neuronal Plasticity; Neurons; Neurotrophic Tyrosine Kinase Receptor Type 2; PHluorin; Prevalence; Reporting; Role; Sensorineural Hearing Loss; Sensory; Signal Transduction; Startle Reaction; Structure; Synapses; Synaptic Transmission; Synaptic plasticity; Testing; Therapeutic; Vertebral column; alcohol consumption during pregnancy; alcohol effect; alcohol exposure; auditory deprivation; auditory processing; hearing impairment; in vivo; in vivo imaging; mimetics; mouse model; otoacoustic emission; patch clamp; prenatal exposure; prepulse inhibition; preservation; receptor; receptor expression; receptor function; trafficking

PROJECT SUMMARY/ABSTRACT Exposure to alcohol during pregnancy produces fetal alcohol spectrum disorders (FASD) that are associated with sensory and cognitive deficits. Individuals with FASD have impaired auditory processing and also frequently exhibit atypical auditory behaviors. Developmental alcohol exposure has been shown to cause impairments in neuronal plasticity including reduction in dendritic spines and alterations in AMPA receptor (AMPAR) function. However, currently there is a gap in understanding how the effects of alcohol on AMPARs alters synaptic plasticity in the intact brain and how changes in AMPAR trafficking can result in alterations in auditory processing. Here, we will use a prenatal exposure mouse model of FASD to investigate the mechanism of auditory processing deficits observed in FASD. We will examine auditory processing in mice prenatally exposed to alcohol, perform in vivo imaging in the primary auditory cortex to track AMPARs and dendritic spines over days, and perform electrophysiological recordings to study AMPAR-mediated synaptic transmission. The goal of the proposal is to provide a mechanistic basis for the altered auditory processing observed in FASD and examine the therapeutic potential of the BDNF mimetic 7,8-Dihydroxy flavone to preserve or restore central auditory processing following fetal alcohol exposure.

项目总结/摘要 妊娠期接触酒精会产生胎儿酒精谱系障碍（FASD）， 感觉和认知缺陷FASD患者的听觉处理功能受损， 表现出非典型的听觉行为发育期酒精暴露已被证明会导致以下方面的损害： 神经元可塑性包括树突棘减少和AMPA受体（AMPAR）功能改变。 然而，目前在理解酒精对AMPAR的影响如何改变突触结构方面存在差距。 完整大脑的可塑性以及AMPAR运输的变化如何导致听觉处理的改变。 在此，我们将使用产前暴露的FASD小鼠模型来研究听觉损伤的机制。 在FASD中观察到的加工缺陷。我们将研究产前暴露于 酒精，在初级听觉皮层中进行体内成像，以跟踪AMPAR和树突棘数天， 并进行电生理记录以研究AMPAR介导的突触传递。的目标 我们的建议是为FASD中观察到的听觉处理改变提供一个机制基础，并检查 脑源性神经营养因子模拟物7，8-二羟基黄酮对听觉中枢保护或恢复的治疗潜力 胎儿酒精暴露后的处理。