Gage F H, Björklund A
Neuroscience. 1986;17(1):89-98. doi: 10.1016/0306-4522(86)90227-7.
The trophic effects of denervation on the survival of fetal cholinergic neuronal cell suspensions grafted to the hippocampal formation of the rat were assessed in the present study. Young adult female rats were injected with cell suspensions of neurons obtained from the fetal basal forebrain region into the hippocampal formation simultaneously with (or without) a fimbria-fornix transection, which removes the hippocampal cholinergic afferents. Four to six months later, one group of grafted animals was evaluated histochemically for: transplant volume; number of acetylcholinesterase-positive cells, and size of acetylcholinesterase-positive cells in the graft. A parallel study was conducted to determine the total number and size of the acetylcholinesterase-positive cells in the septal-diagonal band-substantia innominata complex of the adult rat, to match with the cell survival and growth in the grafts. A second group of grafted rats was taken in parallel for biochemical analysis of choline acetyltransferase activity in the grafted hippocampus. The transplant volume in the rats with fimbria-fornix transection was greater than twice the volume seen in animals without fimbria-fornix lesion. In addition, the number of acetylcholinesterase-positive cells in the transplant was twice as great in the denervated animals as in the non-denervated ones. However, the number of acetylcholinesterase-positive cells per mm3 of graft volume did not differ between the two groups, suggesting that the trophic effect of the denervation was not specific for the cholinergic neurons, but affected the entire grafted tissue. The hippocampal choline acetyltransferase activity of the animals that received the fimbria-fornix lesion simultaneously with transplantation was about three times higher than that of the rats that received grafts but no simultaneous fimbria-fornix transection. A control experiment with animals that received an aspirative lesion of the retrosplenial cortex, transecting the perforant path input, revealed no enhancing effect of hippocampal choline acetyltransferase activity over non-lesioned grafted animals. Thus, the denervation-enhancing effects of the fimbria-fornix lesion appear to be selective and not the result of a general wound-induced mechanism. These results strongly support the contention that neurotrophic factors are released as a result of denervation in the adult hippocampal formation, and that these neurotrophic factors can support survival and growth of central cholinergic neurons. However, the factors involved do not appear to be specific for the cholinergic neurons, but rather have their trophic effects on many types of cells.
在本研究中，评估了去神经支配对移植到大鼠海马结构的胎儿胆碱能神经元细胞悬液存活的营养作用。将年轻成年雌性大鼠同时（或不同时）进行穹窿海马伞横断（去除海马胆碱能传入纤维），并向其海马结构注射从胎儿基底前脑区域获得的神经元细胞悬液。四到六个月后，对一组移植动物进行组织化学评估，以确定：移植体体积；乙酰胆碱酯酶阳性细胞数量，以及移植体中乙酰胆碱酯酶阳性细胞的大小。进行了一项平行研究，以确定成年大鼠隔区-斜角带-无名质复合体中乙酰胆碱酯酶阳性细胞的总数和大小，以与移植体中的细胞存活和生长情况相匹配。另一组移植大鼠同时进行移植海马胆碱乙酰转移酶活性的生化分析。接受穹窿海马伞横断的大鼠的移植体体积比未接受穹窿海马伞损伤的动物的移植体体积大两倍多。此外，去神经支配动物移植体中乙酰胆碱酯酶阳性细胞的数量是未去神经支配动物的两倍。然而，两组每立方毫米移植体体积中乙酰胆碱酯酶阳性细胞的数量并无差异，这表明去神经支配的营养作用并非特异性针对胆碱能神经元，而是影响整个移植组织。同时接受穹窿海马伞损伤和移植的动物的海马胆碱乙酰转移酶活性比仅接受移植但未同时进行穹窿海马伞横断的大鼠高约三倍。对接受压吸性脾后皮质损伤（切断穿通通路输入）的动物进行的对照实验表明，与未损伤的移植动物相比，海马胆碱乙酰转移酶活性没有增强作用。因此，穹窿海马伞损伤的去神经支配增强作用似乎具有选择性，而非一般伤口诱导机制所致。这些结果有力地支持了以下观点：成年海马结构中去神经支配会释放神经营养因子，并且这些神经营养因子能够支持中枢胆碱能神经元的存活和生长。然而，所涉及的因子似乎并非特异性针对胆碱能神经元，而是对多种类型的细胞具有营养作用。
