神经节苷脂GM_1对胚基底前脑移植入Alzheimer病鼠的影响

EFFECTS OF GANGLIOSIDE ON CHOLINERGIC VENTRAL BASAL FOREBRAIN GRAFTS IN THE RAT MODEL OF ALZHEIMER'S DISEASE

用使君子酸毁损大鼠左侧基底大细胞核,制成Alzheimer病模型鼠。2周后进行移植,移植组分单纯胚基底前脑细胞悬液移植组(ST组)和含单唾液酸神经节苷脂(GM_1)的胚基底前脑悬液移植组(GM_1组)。移植后2月、6月行为测试发现,两移植组学习和记忆行为均有改善,GM_1T组行为指标在2月和6月时均与模型组有显著差异。而与正常组无显著差异;ST组仅在6月时与GM_1T组相似。GM_1T组动物在移植前后进行了体感诱发电位检测,结果发现移植前损毁侧正常出现的10 ms正波消失,而在移植后2月和6月时此波重新出现或潜伏期呈轻或中度延长。形态学观察发现,破坏后1周或6月时破坏侧基底大细胞核的AChE阳性细胞大部消失,同侧额、顶叶皮质AChE阳性纤维和终末明显减少。GM_1T组移植区较ST组移植区大。GM_1T组移植区AChE阳性细胞较ST组多而且突起长。两组均见有ChAT免疫阳性细胞。实验表明GM_1能保护植入受体脑内的胚脑细胞并促进它们在受体脑内发育生长并发挥功能效应。

Rats were divided into 4 groups: M group Alzheimer's disease model was established by injecting quisqualic acid into the left nucleus basalis magnocellularis(NBM); ST group-suspension of fetal ventral basal forebrain was transplanted by injecting it into the frontal and parietal cortex(8μ1 each) on the lesion side of the model rat; GM_1T group-Cholinergic neuronal suspension containing ganglioside (GM_1) was injected (4μg/8μl each) in the same way; and N group-normal rats were used as control. Two and six months after grafting, the passive and active avoidance tests were carried out. The results showed that the learning and memory behaviour were improved in the grafted groups. There were significant difference (P<0.05) between GM_1T group and model rats and no significant difference (P>0.05) between GM_1T group and normal rats either at two or six months period. Whereas in ST group the same values were only found at six months. Somatosensory evoked potential (SEP) was recorded in GM_1T rats before and after grafting. The results showed that there was a distinct initial positive wave with an incubation period of 10 ms on the normal side and it was disappeared on the lesioned side before grafting, whereas it was restored or reappeared with its incubation period slightly prolonged at two or six months after grafting. The morphological results indicated that the AChE positive neurons of NBM was destroyed on lesioned side either in one week or six post-lesion months. AChE positive terminals were reduced in number in the frontal and parietal cortex ipsilateral to the lesion. The extent of the graft area was bigger and the number of AChE positive neurons was larger and their processes extended longer in GM_1T group than those in the ST group. These findings suggest that the ganglioside can prevent the cholinergie deficit by protecting the cholinergic neurons of fetal basal forebrain and promoting the survival and growth of neurons and ameliorate the behavioural deficits.