Petit T L, Biederman G B, Jonas P, LeBoutillier J C
Exp Neurol. 1985 Jun;88(3):640-51. doi: 10.1016/0014-4886(85)90077-9.
Aluminum (Al) is known to be a neurotoxic agent in some species, inducing neurofibrillary tangles, dendritic atrophy, and behavioral deterioration, and has been implicated as a possible agent in human Alzheimer's disease and dialysis dementia. This study was conducted to assess the neurotoxic effects of Al in infant rabbits, and to compare the effects to those previously observed to follow exposure in the adult animal. Aluminum tartrate (2 microM) or physiologic saline was injected into the right lateral ventricle of 2-day-old (day P3) New Zealand white rabbits. The animals were trained in a step-down active avoidance task on P12 and retested 1 day later. They were killed on P20, and their hippocampal CA1 pyramidal cells examined for neurofibrillary tangles or prepared with the rapid Golgi stain for an examination of dendritic development. Additional animals were similarly infused with 1 or 3 microM Al for qualitative and some quantitative observations. No overt neurologic signs were observed in the 1- or 2-microM groups, however, most of the 3-microM group died between P10 and P20. Although there were no significant differences between the 2-microM and control animals on either learning or retention of the active avoidance task, deficits in retention of the task were observed in the 3-microM group. Neurofibrillary tangles in CA1 pyramidal cells were observed with dosages of 1 microM and higher. In the 2-microM group, the pattern of dendritic arborization in CA1 pyramidal cells was consistent with that expected for cells retarded in their development. These results have implications in terms of developmental differences in the neurobehavioral effects of Al.
已知铝(Al)在某些物种中是一种神经毒性剂,可诱发神经原纤维缠结、树突萎缩和行为退化,并且被认为可能是导致人类阿尔茨海默病和透析性痴呆的一种因素。本研究旨在评估铝对幼兔的神经毒性作用,并将这些作用与先前观察到的成年动物暴露后的作用进行比较。将酒石酸铝(2微摩尔)或生理盐水注入2日龄(出生后第3天)的新西兰白兔的右侧脑室。在出生后第12天对这些动物进行逐步下降主动回避任务训练,并在1天后重新测试。它们在出生后第20天被处死,检查其海马CA1锥体细胞有无神经原纤维缠结,或用快速高尔基染色法制备标本以检查树突发育。另外的动物以同样方式注入1或3微摩尔铝以进行定性和一些定量观察。在1微摩尔或2微摩尔组中未观察到明显的神经体征,然而,3微摩尔组的大多数动物在出生后第10天至第20天之间死亡。虽然在主动回避任务的学习或记忆方面,2微摩尔组与对照组动物之间没有显著差异,但在3微摩尔组中观察到任务记忆存在缺陷。在剂量为1微摩尔及更高时,观察到CA1锥体细胞中有神经原纤维缠结。在2微摩尔组中,CA1锥体细胞的树突分支模式与发育迟缓细胞预期的模式一致。这些结果对铝的神经行为效应的发育差异具有启示意义。