孕期酒精暴露对小鼠视皮质神经元树突棘和突触的影响
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摘要
酒精滥用可以导致多组织和器官的损伤,主要影响部位是脑、肝、心血管系统和免疫系统。胎儿酒精综合征(FAS)就是由于孕期母体酒精暴露所导致的胎儿和儿童的严重损害。由于树突棘和突触在学习和记忆方面的特殊功能,因此人们常用它们在孕期或出生后酒精暴露中出现的病理改变来解释患者神经行为障碍的成因。为了更好的揭示孕期酒精暴露对突触和树突棘发育的影响,我们分析了P0—P30生前酒精暴露小鼠视皮质中树突棘和突触的超微结构,及其长时程效应。从妊娠第5天(E5)开始用酒精灌胃直至子鼠出生,建立FAS动物模型。采用DiI散射的方法标记视皮质锥体细胞树突棘,利用透射电子显微镜观察突触的超微结构。结果显示:1.在胚胎15天(E15)可以观察到不成熟的新生的突触,突触前终末内有临近胞体或突起的多形囊泡,突触后膜属于非特化部分,在突触前、后膜之间的突触间隙只有5~10 nm,要比成熟的突触间隙狭窄。随着年龄的增加突触前、后膜逐渐增厚,突触间隙增宽至15~20 nm。到p7时才能看到成熟的突触超微结构,这个时期可观察到Gray’s I型和II型突触。而突触的成熟与树突棘的分化是同步的,突触的特化可能依赖于树突棘的成熟和突触前囊泡成分的表达。同时,研究显示出突触的发生与新皮质的发育和成熟密切相关。2.孕期酒精暴露能够诱导子鼠视皮质锥体细胞树突棘的密度降低、长度增加,该变化具有剂量依赖性和长时程效应。同时突触超微结构也出现一定的改变,如:突触小泡减少和突触间隙变窄。树突棘和突触超微结构的改变可能是视皮质发育滞后的一种表现,其长时程效应则可能是儿童时期FAS中出现智力低下的一种原因。
Alcohol abuse causes injuries of multiple organs and tissues affecting the brain, liver, cardiovascular system, immune system. Fetal alcohol syndrome (FAS) is a serious injury to fetus and child caused by maternal prenatal exposure. Due to their specific functions in learning and memory, the pathologic alterations of synapses and dendritc spines should be used to explain the neurobehavioral deficits after prenatal or postnatal alcohol exposure. To better understand the development of synapse and dendritic spine after prenatal alcohol exposure, we analyzed dendritic spines and synaptic ultrastucture in visual cortex of mice from P0-P30 after prenatal ethanol consumption, and the dose-dependent and long-term affecting alterations of synapse and dendritic spine were investigated in visual cortex. Pregnant mice were intubated ethanol daily from E5 through the pup’s birth to establish mode of prenatal alcohol abuse. The dendritic spines of pyramidal cells in visual cortex of pups were labeled with DiI diolistic assay, and the synaptic ultrastructure was observed under transmission electron microscope. The results show: 1.Nascent synapses were seen as early as E15, although these were immature and were composed of a presumed presynaptic terminal with pleiomorphic vesicles in the vicinity of a partner cell body or projection. The postsynaptic plasmalemma remained unspecialized and the gap between pre- and postsynaptic plasmalemmas was only 5-10 nm, significantly narrower than the mature synaptic cleft. With increasing age there was gradual thickening of both the pre- and postsynaptic membranes, with widening of the synaptic cleft to 15-20 nm. Ultrastructurally mature synapses were not seen until P7; at this time both Gray’s type I and II could be observed. Synapse maturation was synchronous with dendritic spine differentiation, synaptic specialization may be dependent on dendritic spine maturation and the expression of presynaptic vesicle components. In the meantime, the study also indicated that the synaptogenesis was connected with the development and maturation of neocortex. 2. Prenatal alcohol exposure could induce dendritic spines of pyramidal neurons in visual cortex to decrease in their number and elongate in their length. These changes are dose-dependent with long term effect even at postnatal 30. The ultrastructural alterations could also be found in synapse, for example, decreased synaptic vesicle, narrow synaptic cleft. The alterations of dendritic pine and synaptic ultrastructure probably were the manifestations of the retardation of visual cortical development. Their long-term effect is one of the causes of lifelong mental retardation of FAS in childhood.
Alcohol abuse causes injuries of multiple organs and tissues affecting the brain, liver, cardiovascular system, immune system. Fetal alcohol syndrome (FAS) is a serious injury to fetus and child caused by maternal prenatal exposure. Due to their specific functions in learning and memory, the pathologic alterations of synapses and dendritc spines should be used to explain the neurobehavioral deficits after prenatal or postnatal alcohol exposure. To better understand the development of synapse and dendritic spine after prenatal alcohol exposure, we analyzed dendritic spines and synaptic ultrastucture in visual cortex of mice from P0-P30 after prenatal ethanol consumption, and the dose-dependent and long-term affecting alterations of synapse and dendritic spine were investigated in visual cortex. Pregnant mice were intubated ethanol daily from E5 through the pup’s birth to establish mode of prenatal alcohol abuse. The dendritic spines of pyramidal cells in visual cortex of pups were labeled with DiI diolistic assay, and the synaptic ultrastructure was observed under transmission electron microscope. The results show: 1.Nascent synapses were seen as early as E15, although these were immature and were composed of a presumed presynaptic terminal with pleiomorphic vesicles in the vicinity of a partner cell body or projection. The postsynaptic plasmalemma remained unspecialized and the gap between pre- and postsynaptic plasmalemmas was only 5-10 nm, significantly narrower than the mature synaptic cleft. With increasing age there was gradual thickening of both the pre- and postsynaptic membranes, with widening of the synaptic cleft to 15-20 nm. Ultrastructurally mature synapses were not seen until P7; at this time both Gray’s type I and II could be observed. Synapse maturation was synchronous with dendritic spine differentiation, synaptic specialization may be dependent on dendritic spine maturation and the expression of presynaptic vesicle components. In the meantime, the study also indicated that the synaptogenesis was connected with the development and maturation of neocortex. 2. Prenatal alcohol exposure could induce dendritic spines of pyramidal neurons in visual cortex to decrease in their number and elongate in their length. These changes are dose-dependent with long term effect even at postnatal 30. The ultrastructural alterations could also be found in synapse, for example, decreased synaptic vesicle, narrow synaptic cleft. The alterations of dendritic pine and synaptic ultrastructure probably were the manifestations of the retardation of visual cortical development. Their long-term effect is one of the causes of lifelong mental retardation of FAS in childhood.
引文
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