Yamamoto T
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Yakubutsu Seishin Kodo. 1991 Aug;11(4):223-35.
Alzheimer's disease is characterized pathologically by the development of numerous neuritic plaques (NP) and neurofibrillary tangles (NFT) within the brain. Recent studies of Alzheimer's disease patients have uniformly shown marked impairment on odor recognition. In Alzheimer's disease, brain structures closely related to the olfactory bulb (OB) or the olfactory system demonstrate significantly histopathological changes. Anatomically, the olfactory bulbs project through the lateral olfactory tracts to the olfactory tubercules, the pyriform cortex, the cortical amygdala nucleus, and the ventrolateral entorhinal area. In addition, the olfactory system is particularly rich in acetylcholine and other neurotransmitters, many of which are deficient in Alzheimer's disease. Furthermore, increased numbers of NP and NFT in the OB and anterior olfactory nucleus have been demonstrated in patients with Alzheimer's disease. These findings suggest that there is a close correlation between the impairment of olfactory processes and the course of Alzheimer's disease. In animal study, many investigators have become interested in the role that olfactory cues play in learning/memory. Bilateral olfactory bulbectomy in rats impairs passive avoidance and radial-maze task in acquisition. In both working and reference memory tasks using a 3-panel runway apparatus, OB-lesioned rats showed a marked increase of errors (pushes made on the two incorrect panels of the 3-panel gates located at 4 choice points). Furthermore, in 3-lever operant task using a delayed matching-to-lever location procedure, OB lesions decreased significantly the correct response in test trials without affecting that in training trials. These findings indicate that olfactory bulbectomy leads to severe impairment of memory in rats. Interestingly, the appearance of memory impairment is delayed following OB lesions. Earlier studies also had shown that the rats do not require olfactory cues for efficient performance in some learning task. Judging from these findings, the impairment of memory do not attribute solely to olfactory deficit. Therefore, it seems likely that the impairment of memory following the bulbectomy might be due to secondary degeneration in several areas projected from the OB rather than to the olfactory deficit. Unfortunately, investigation of the mechanism underlying the development of Alzheimer's disease has been hampered by the lack of an animal model. In this context, as reviewed here, since OB-lesioned rats show severe impairment of memory with some emotional changes, the olfactory bulbectomy syndrome may be a useful model of Alzheimer's disease. Such a review inevitably raises more questions than its answers, but it is hoped that it may stimulate further investigation in this new field.
阿尔茨海默病的病理特征是大脑中出现大量神经炎性斑块（NP）和神经原纤维缠结（NFT）。对阿尔茨海默病患者的近期研究一致显示其在气味识别方面存在明显损害。在阿尔茨海默病中，与嗅球（OB）或嗅觉系统密切相关的脑结构表现出显著的组织病理学变化。从解剖学角度来看，嗅球通过外侧嗅束投射至嗅结节、梨状皮质、皮质杏仁核以及腹侧内嗅区。此外，嗅觉系统中乙酰胆碱和其他神经递质特别丰富，而在阿尔茨海默病中许多此类神经递质会缺乏。此外，已证实在阿尔茨海默病患者的嗅球和前嗅核中，NP和NFT的数量增加。这些发现表明嗅觉功能障碍与阿尔茨海默病的病程之间存在密切关联。在动物研究中，许多研究者对嗅觉线索在学习/记忆中所起的作用产生了兴趣。大鼠双侧嗅球切除会损害其在习得过程中的被动回避和放射状迷宫任务。在使用三面板跑道装置的工作记忆和参考记忆任务中，嗅球损伤的大鼠错误（在位于4个选择点的三面板门的两个错误面板上的推压）显著增加。此外，在使用延迟杠杆位置匹配程序的三杠杆操作性任务中，嗅球损伤在测试试验中显著降低了正确反应，而不影响训练试验中的正确反应。这些发现表明嗅球切除会导致大鼠严重的记忆障碍。有趣的是，嗅球损伤后记忆障碍的出现会延迟。早期研究还表明，大鼠在某些学习任务中高效表现并不需要嗅觉线索。从这些发现来看，记忆障碍并非仅仅归因于嗅觉缺陷。因此，嗅球切除后出现的记忆障碍可能是由于从嗅球投射的几个区域的继发性变性，而非嗅觉缺陷所致。不幸的是，由于缺乏动物模型，对阿尔茨海默病发病机制的研究受到了阻碍。在此背景下，如本文所综述的，由于嗅球损伤的大鼠表现出严重的记忆障碍并伴有一些情绪变化，嗅球切除综合征可能是阿尔茨海默病的一个有用模型。这样一篇综述不可避免地引发的问题比给出的答案更多，但希望它能激发在这个新领域的进一步研究。
