Jeltsch H, Cassel J C, Neufang B, Kelche C, Hertting G, Jackisch R, Will B
L.N.B.C., U.P.R. 419 du C.N.R.S., Centre de Neurochimie, Strasbourg, France.
Neuroscience. 1994 Nov;63(1):19-39. doi: 10.1016/0306-4522(94)90004-3.
Long-Evans female rats sustained electrolytic lesions of the fimbria and the dorsal fornix and, two weeks later, received intrahippocampal suspension grafts of fetal tissue. The grafts were prepared from regions including either the medial septum and the diagonal band of Broca (septal grafts), or the mesencephalic raphe (raphe grafts), or from both these regions together (co-grafts). All rats were submitted to a series of behavioural tests (home cage and open-field locomotion, spontaneous alternation, radial-arm maze and Morris water maze performance) run over two periods after grafting (one to nine weeks and 20-35 weeks). Two weeks after completion of behavioural testing, histological (acetylcholinesterase and Cresyl Violet staining) and/or neurochemical (choline acetyltransferase activity, high-affinity synaptosomal uptake of choline and serotonin, noradrenaline, serotonin and 5-hydroxyindolacetic acid concentrations) verifications were performed on the hippocampus. Compared to sham-operated rats, lesion-only rats exhibited hyperactivity which was transient in a familiar environment (home cage) and lasting in an unfamiliar one (open field), decreased rates of spontaneous T-maze alternation, and impaired memory performance in both the radial-arm maze and the Morris water maze. These rats also showed decreased cholinergic and serotonergic markers with a maximal depletion in the septal two-thirds of the hippocampus. Noradrenaline concentration tended to be increased in the dorsal third of the hippocampus, but was not modified in the other two-thirds. While septal grafts specifically increased the cholinergic markers and raphe grafts the serotonergic ones, neither of these grafts produced a lasting effect on any behavioural variable. Conversely, the co-grafts, which increased both the cholinergic and serotonergic markers in the septal two-thirds of the hippocampus, completely normalized the Morris water maze probe trial performance, but failed to affect any of the other behavioural variables. Our present results confirm that grafts of fetal neurons injected into the denervated hippocampus may induce a neurochemical recovery that depends on the anatomical origin of the grafted cells, and that co-grafting two fetal brain regions allows the combination of their individual neurochemical properties. Furthermore, our results show that these neurochemical effects of the co-grafts may be involved in the recovery of behavioural function observed in the water maze. However, somewhat paradoxically, those effects appear inefficient for inducing any recovery in other behavioural tasks, even in the radial-arm maze; which is assumed to measure similar spatial functions.(ABSTRACT TRUNCATED AT 400 WORDS)
将成年雄性Long-Evans大鼠的穹窿和背侧穹窿进行电解损伤，两周后，将胎儿组织的海马内悬浮移植物植入大鼠体内。移植物取自包括内侧隔区和布罗卡斜角带（隔区移植物）、中脑缝际核（缝际核移植物）或这两个区域一起（联合移植物）的区域。所有大鼠在移植后的两个阶段（1至9周和20至35周）接受一系列行为测试（笼内和旷场运动、自发交替、放射状臂迷宫和莫里斯水迷宫表现）。行为测试完成两周后，对海马进行组织学（乙酰胆碱酯酶和甲酚紫染色）和/或神经化学（胆碱乙酰转移酶活性、胆碱和5-羟色胺、去甲肾上腺素、5-羟色胺和5-羟吲哚乙酸浓度的高亲和力突触体摄取）验证。与假手术大鼠相比，仅损伤大鼠表现出多动，在熟悉环境（笼内）中是短暂的，在不熟悉环境（旷场）中是持续的，自发T迷宫交替率降低，在放射状臂迷宫和莫里斯水迷宫中的记忆表现受损。这些大鼠还显示胆碱能和5-羟色胺能标记物减少，在海马隔区的三分之二处有最大程度的消耗。去甲肾上腺素浓度在海马背侧三分之一处有升高趋势，但在其他三分之二处未改变。虽然隔区移植物特异性增加胆碱能标记物，缝际核移植物增加5-羟色胺能标记物，但这些移植物对任何行为变量都没有产生持久影响。相反，联合移植物增加了海马隔区三分之二处的胆碱能和5-羟色胺能标记物，使莫里斯水迷宫探测试验表现完全正常化，但未能影响任何其他行为变量。我们目前的结果证实，注入去神经海马的胎儿神经元移植物可能诱导一种依赖于移植细胞解剖来源的神经化学恢复，并且联合移植两个胎儿脑区可以使它们各自的神经化学特性相结合。此外,我们的结果表明，联合移植物的这些神经化学作用可能参与了在水迷宫中观察到的行为功能恢复。然而，有点自相矛盾的是，这些作用在诱导其他行为任务中的任何恢复方面似乎效率不高，即使在放射状臂迷宫中也是如此；放射状臂迷宫被认为测量的是类似的空间功能。（摘要截断于400字）
