Homer2 is necessary for EtOH-induced neuroplasticity
Homer2 is necessary for EtOH-induced neuroplasticity
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DOI：
10.1523/jneurosci.1529-05.2005
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发表时间：
2005-07-27
影响因子：
5.3
通讯作者：
Kalivas, PW
中科院分区：
文献类型：
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作者：
Szumlinski, KK;Lominac, KD;Kalivas, PW
Homer蛋白是调节谷氨酸信号传导和突触可塑性的蛋白质组装的组成部分。组成型Homer 2基因缺失[敲除（KO）]和用腺相关病毒（AAV）转染Homer 2b的拯救用于证明Homer蛋白在通过重复乙醇（EtOH）施用产生的神经可塑性中的重要性。Homer2 KO小鼠避免饮用高浓度的EtOH，并且在重复EtOH给药后未出现位置偏好或运动致敏。缺乏行为可塑性EtOH后Homer2删除是由于缺乏增强细胞外多巴胺和谷氨酸引起的反复EtOH注射的上升。通过AAV介导的Homer2b转染入Alcobens细胞，EtOH诱导的行为和神经化学变化的基因型差异基本上被逆转，包括EtOH偏好、运动致敏和EtOH诱导的细胞外谷氨酸和多巴胺升高的差异。这些数据表明，在调节EtOH诱导的行为和细胞神经可塑性的必要的和积极的作用，为hemorbens Homer2的表达。
Homer proteins are integral to the assembly of proteins regulating glutamate signaling and synaptic plasticity. Constitutive Homer2 gene deletion [ knock- out ( KO)] and rescue with adeno- associated viral ( AAV) transfection of Homer2b was used to demonstrate the importance of Homerproteins in neuroplasticity produced by repeated ethanol ( EtOH) administration. Homer2 KO mice avoided drinking high concentrations of EtOH and did not develop place preference or locomotor sensitization after repeated EtOH administration. The deficient behavioral plasticity to EtOH after Homer2 deletion was paralleled by a lack of augmentation in the rise in extracellular dopamine and glutamate elicited by repeated EtOH injections. The genotypic differences in EtOH- induced change in behavior and neurochemistry were essentially reversed by AAV- mediated transfection of Homer2b into accumbens cells including, differences in EtOH preference, locomotor sensitization, and EtOH- induced elevations in extracellular glutamate and dopamine. These data demonstrate a necessary and active role for accumbens Homer2 expression in regulating EtOH- induced behavioral and cellular neuroplasticity.