Dalrymple-Alford J C
Department of Psychology, University of Canterbury, Christchurch, New Zealand.
Brain Res. 1994 Oct 24;661(1-2):243-58. doi: 10.1016/0006-8993(94)91201-7.
There are many reports that basal forebrain grafts ameliorate behavioral impairments produced by dorsal septo-hippocampal pathway lesions, but several studies have either found that this recovery may be unrelated to concomitant restitution of cholinergic markers, may be modest and depend on certain experimental conditions or instead that grafts may actually exacerbate lesion-induced impairments. In this study, rats received one of three lesions of the dorsal septo-hippocampal pathways or a sham lesion, at 32 days of age, and intrahippocampal basal forebrain grafts or the vehicle control 10 days later. In grafted rats with total aspirative lesion of the fimbria-fornix, there was a substantial AChE-positive hippocampal reinnervation but no improvement of the severe lesion-induced spatial learning deficits, either reference memory or working memory, whether tested at 1 or 5 months post-grafting. In rats with bilateral medial fimbria lesions, grafts were successful, normal in appearance and produced substantial hippocampal cholinergic reinnervation; relative to non-grafted counterparts, however, grafted medial fimbria rats showed an early reference memory impairment and a persistent exacerbation of a working memory deficit. Exacerbation of learning impairments was also apparent in grafted rats with partial hippocampal denervation due to lesion of the cingulate and adjacent cortex above the fimbria-fornix. Nonetheless, basal forebrain grafts normalised general activity in these lesion groups, irrespective of whether the lesion-induced change was an increase or a decrease relative to controls. Graft-derived lesion groups, irrespective of whether the lesion-induced change was an increase or a decrease relative to controls. Graft-derived AChE-positive innervation was more marked than expected in both grafted cingulate-lesioned rats and grafted sham-lesioned rats, while control grafts of fetal cortex (above the septum) produced little or no AChE-positive innervation. Size of basal forebrain grafts, originally 3 microliters at two dorsal sites per hippocampus, increased markedly from rostral to caudal dorsal hippocampus in all groups but did not differ significantly across grafted groups, even with respect to non-lesioned rats. This study adds further evidence that basal forebrain grafts, successful with respect to cholinergic reinnervation, do not always enhance cognitive functions in rat hippocampal lesion models, and confirms that these grafts may have adverse effects after partial septo-hippocampal system lesions. It is important to attend to both the potential negative and positive effects of neural grafts.
有许多报道称，基底前脑移植可改善背侧隔区 - 海马通路损伤所导致的行为障碍，但一些研究发现，这种恢复可能与胆碱能标志物的同时恢复无关，可能程度有限且取决于某些实验条件，或者相反，移植实际上可能会加剧损伤诱导的障碍。在本研究中，大鼠在32日龄时接受背侧隔区 - 海马通路的三种损伤之一或假损伤，10天后接受海马内基底前脑移植或载体对照。在接受穹窿 - 海马全吸除损伤的移植大鼠中，海马有大量乙酰胆碱酯酶（AChE）阳性的神经再支配，但严重损伤诱导的空间学习缺陷，无论是参考记忆还是工作记忆，在移植后1个月或5个月进行测试时均未得到改善。在双侧内侧穹窿损伤的大鼠中，移植成功，外观正常并产生大量海马胆碱能神经再支配；然而，相对于未移植的大鼠，移植内侧穹窿的大鼠表现出早期参考记忆损伤和工作记忆缺陷的持续加剧。由于扣带回和穹窿 - 海马上方相邻皮质的损伤导致部分海马去神经支配的移植大鼠中，学习障碍的加剧也很明显。尽管如此，基底前脑移植使这些损伤组的一般活动正常化，无论损伤诱导的变化相对于对照组是增加还是减少。移植衍生的损伤组，无论损伤诱导的变化相对于对照组是增加还是减少。在移植的扣带回损伤大鼠和移植的假损伤大鼠中，移植衍生的AChE阳性神经支配比预期更明显，而胎儿皮质（隔区上方）的对照移植产生很少或没有AChE阳性神经支配。基底前脑移植的大小，最初在每个海马的两个背侧部位为3微升，在所有组中从海马背侧的头端到尾端显著增加，但移植组之间没有显著差异，即使是未损伤的大鼠也是如此。这项研究进一步证明，在胆碱能神经再支配方面成功的基底前脑移植并不总是能增强大鼠海马损伤模型中的认知功能，并证实这些移植在部分隔区 - 海马系统损伤后可能产生不利影响。关注神经移植的潜在负面和正面影响很重要。
