Bianchi M, Fone K F C, Azmi N, Heidbreder C A, Hagan J J, Marsden C A
Institute of Neuroscience, School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
Eur J Neurosci. 2006 Nov;24(10):2894-902. doi: 10.1111/j.1460-9568.2006.05170.x. Epub 2006 Nov 20.
Social isolation from weaning affects hippocampal structure and function in the rat. The intrinsic dynamic instability of the cytoskeletal microtubular system is essential for neuronal development and organization. Accordingly, the present paper investigated the effects of social isolation on hippocampal levels of alpha-tubulin isoforms associated with microtubule dynamics, the dendritic marker MAP-2 and alterations in locomotor activity and recognition memory. Male Lister Hooded rats (postnatal day 25-28) were housed either in groups or singly (isolated animals) for 30 days. Locomotor activity in a novel arena and novel object recognition were monitored in activity boxes. The hippocampus was dissected out 18 h after the novel object recognition task. Levels of alpha-tubulin isoforms and MAP-2 were analysed using Western blots. The experiments were conducted in duplicate, using two batches of rats obtained from different suppliers. Isolated animals were hyperactive and showed recognition memory deficits in the novel object recognition task. These behavioural alterations were accompanied by specific alterations in hippocampal alpha-tubulin isoforms and decreased MAP-2 expression. The results confirm that rearing rats in isolation produces hyperactivity and cognitive deficits. The behavioural alterations were accompanied by hippocampal cytoskeletal changes consistent with microtubule stabilization, and by decreased MAP-2 expression. These findings are indicative of an abnormal development of synaptic connections and/or reductions in neuronal cell number. The developmental structural abnormalities in the hippocampus may contribute to the cognitive impairments which result from isolation rearing in rats.
断奶后社交隔离会影响大鼠海马体的结构和功能。细胞骨架微管系统固有的动态不稳定性对神经元的发育和组织至关重要。因此,本文研究了社交隔离对与微管动力学相关的α-微管蛋白亚型的海马水平、树突标记物MAP-2以及运动活动和识别记忆改变的影响。雄性利斯特戴帽大鼠(出生后第25 - 28天)被成组饲养或单独饲养(隔离动物)30天。在活动箱中监测新环境中的运动活动和新物体识别。在新物体识别任务后18小时取出海马体。使用蛋白质免疫印迹法分析α-微管蛋白亚型和MAP-2的水平。实验重复进行,使用从不同供应商获得的两批大鼠。隔离动物表现为多动,并且在新物体识别任务中表现出识别记忆缺陷。这些行为改变伴随着海马α-微管蛋白亚型的特定改变以及MAP-2表达的降低。结果证实,单独饲养大鼠会导致多动和认知缺陷。行为改变伴随着与微管稳定一致的海马细胞骨架变化以及MAP-2表达的降低。这些发现表明突触连接发育异常和/或神经元细胞数量减少。海马体发育结构异常可能导致大鼠因隔离饲养而产生的认知障碍。