Effects of Developmental Alcohol Exposure on Astrocyte Ca2+ Signaling and Structural Synaptic Plasticity

发育期酒精暴露对星形胶质细胞 Ca2 信号传导和结构突触可塑性的影响

• 批准号: 9761943
• 负责人: Padmashri Ragunathan
• 金额: $ 18万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9761943
• 关键词: Affect; Alcohols; Animal Model; Astrocytes; Attention; Behavioral; Brain; Brain region; Child; Dendritic Spines; Development; Exhibits; Fetal Alcohol Exposure; Fetal Alcohol Spectrum Disorder; Forelimb; Functional disorder; Goals; Image; Impaired cognition; Impairment; Injections; Label; Language Development; Learning; Memory; Modeling; Monitor; Motor; Motor Cortex; Motor Skills; Mus; Neuronal Plasticity; Neurons; Neuropsychology; Pregnancy; Process; Reporting; Role; Signal Transduction; Slice; Structure; Synapses; Synaptic plasticity; Testing; Therapeutic; Vertebral column; Viral Vector; Visuospatial; alcohol exposure; brain abnormalities; design; designer receptors exclusively activated by designer drugs; executive function; experience; imaging modality; improved; in vivo; in vivo imaging; insight; motor control; motor learning; motor skill learning; mouse model; prenatal exposure; social; therapeutic target

Abstract Exposure to alcohol during pregnancy produces fetal alcohol spectrum disorders (FASD) which is associated with cognitive impairments in various neuropsychological domains. Children with FASD often exhibit sensorimotor dysfunctions that include deficits in motor coordination and fine motor control. Although developmental alcohol exposure has been shown to affect astrocytes and cause impairments in neuronal plasticity in several brain regions, very little is known about alterations in astrocytic Ca2+ signaling and synaptic changes that occur in the intact brain. Here we will use prenatal exposure mouse model of fetal alcohol spectrum disorders to study alcohol-induced alterations in basal and motor-skill learning induced astrocytic Ca2+ signaling and structural synaptic plasticity. We will combine in vivo imaging of dendritic spines with astrocytic Ca2+ imaging under basal conditions and with learning. The goal of the proposal is to determine whether developmental alcohol exposure results in alterations in basal and motor-skill learning induced astrocytic Ca2+ signaling and structural synaptic plasticity.

摘要 怀孕期间接触酒精会导致胎儿酒精谱系障碍（FASD）， 与各种神经心理学领域的认知障碍有关。患有FASD的儿童经常 表现出感觉运动功能障碍，包括运动协调和精细运动控制的缺陷。 虽然发育期的酒精暴露已被证明会影响星形胶质细胞并导致损伤 在几个脑区的神经元可塑性中，对星形胶质细胞Ca ~（2+）的改变知之甚少。 信号和突触的变化发生在完整的大脑。在这里，我们将使用产前暴露小鼠 研究酒精诱导的基础和运动技能改变的胎儿酒精谱系障碍模型 学习诱导星形胶质细胞Ca 2+信号和结构突触可塑性。我们将在体内联合收割机 在基础条件和学习条件下用星形胶质细胞Ca 2+成像对树突棘进行成像。的 该提案的目标是确定发育中的酒精暴露是否会导致 基础和运动技能学习诱导星形胶质细胞Ca 2+信号传导和结构突触可塑性。