Leanza G, Martìnez-Serrano A, Björklund A
Wallenberg Neuroscience Center, Lund University, Sweden.
Eur J Neurosci. 1998 Jul;10(7):2353-70. doi: 10.1046/j.1460-9568.1998.00247.x.
Impairments in learning and memory, induced by surgical or excitotoxic lesions of the septo-hippocampal or basalo-cortical pathways, can be ameliorated by grafts of cholinergic-rich foetal basal forebrain tissue into the hippocampus and/or neocortex. However, the effects of such grafts have been only partial, which may be due to the non-specific nature of the lesioning procedures used in these studies, known to destroy both cholinergic and non-cholinergic neuronal projections. In the present study, we have explored the effects of cholinergic-rich grafts in rats subjected to selective cholinergic lesions, induced by intraventricular injections of the immunotoxin 192 IgG-saporin. This lesion, which selectively destroyed 85-95% of the cholinergic neurons in both the septal-diagonal band and nucleus basalis, produced a long-lasting, substantial impairment in both the acquisition of spatial reference memory in the Morris water maze task and delay-dependent short-term memory performance, as seen in a delayed matching-to-position test. Foetal cholinergic grafts (but not control grafts of cerebellar tissue) implanted at multiple sites into both the hippocampus and fronto-parietal neocortex, bilaterally, completely reversed the acquisition deficit in place navigation in the water maze, to an extent that greatly exceeded that previously seen in animals with non-selective lesions. Most notably, however, the impairment in short-term memory was only partially and inconsistently affected, and only at the longest delay times. The morphological analysis, performed at about 7 months after transplantation, showed that the grafts had re-established a close to normal cholinergic innervation in the initially denervated cortical and hippocampal territories. It is proposed that the differential effects of cholinergic-rich transplants on different aspects of cognitive performance may define intrinsic limitations to the functional capacity of the ectopically placed grafts, which may be due to incomplete integration of the grafted cholinergic neurons into functional regulatory circuitries normally available to the basal forebrain cholinergic system.
经手术或通过隔海马或基底皮质通路的兴奋性毒性损伤所诱发的学习和记忆障碍，可通过将富含胆碱能的胎儿基底前脑组移植到海马体和/或新皮质中得到改善。然而，此类移植的效果只是部分性的，这可能是由于这些研究中所采用的损伤程序具有非特异性，已知这些程序会破坏胆碱能和非胆碱能神经元投射。在本研究中，我们探究了富含胆碱能的移植对接受选择性胆碱能损伤的大鼠的影响，该损伤由脑室内注射免疫毒素192 IgG-皂草素所诱发。这种损伤选择性地破坏了隔角带和基底核中85-95%的胆碱能神经元，在莫里斯水迷宫任务中对空间参考记忆的获取以及在延迟位置匹配测试中所观察到的延迟依赖性短期记忆表现均产生了持久且显著的损伤。双侧在多个部位将胎儿胆碱能移植体（而非小脑组织的对照移植体）植入海马体和额顶叶新皮质，完全逆转了水迷宫中位置导航的获取缺陷，其程度大大超过了先前在非选择性损伤动物中所观察到的情况。然而，最值得注意的是，短期记忆损伤仅受到部分且不一致的影响，且仅在最长延迟时间时出现。在移植后约7个月进行的形态学分析表明，移植体在最初去神经支配的皮质和海马区域重新建立了接近正常的胆碱能神经支配。有人提出，富含胆碱能的移植对认知表现不同方面的不同影响可能界定了异位移植体功能能力的内在局限性，这可能是由于移植的胆碱能神经元未完全整合到基底前脑胆碱能系统通常可利用的功能调节回路中所致。
