Decombe R, Rivot J P, Aunis D, Abrous N, Peschanski M, Herman J P
INSERM U-259, Université Bordeaux II, Bordeaux, France.
Exp Neurol. 1990 Feb;107(2):143-53. doi: 10.1016/0014-4886(90)90152-i.
The aim of the present experiments was to test whether adrenal chromaffin cells implanted into the striatum of rats could exert a functional effect through a release of catecholamines. A cell suspension obtained from bovine adrenal medulla was implanted unilaterally into the striatum. The striatal dopaminergic input was extensively destroyed beforehand to preclude the possibility of reinnervation of the striatum by endogenous dopaminergic neurons. The functional influence of the implant was tested through the measurement of drug-induced rotation, while catecholamine release was measured subsequently in the same animals by in vivo electrochemistry. Transplant survival, as shown by the immunohistochemical analysis performed at the end of the in vivo experiments, was highly variable. Surviving chromaffin cells maintained their endocrine morphology and no reinnervation of the host striatum could be detected. Rotation of the animals evoked by apomorphine (0.1 mg/kg, sc) or amphetamine (5.0 mg/kg, ip) following the lesion was left uninfluenced following transplantation, even when a large transplant was recovered. On the other hand, nicotine (0.5 mg/kg, sc) evoked a strong contraversive rotational response in the transplant-bearing animals. This response could not be ascribed to the central effect of substances released peripherally and entering the nervous system through the blood-brain barrier opened by the implantation procedure, as it could not be found in animals bearing implants of other peripheral endocrine tissue, viz, pituitary. The effect of nicotine was not blocked by the pretreatment of the animals with either the opiate antagonist naloxone (2.5 mg/kg, 10 min) or the dopamine receptor blocker pimozide (0.5 mg/kg, 1 h), although the latter pretreatment blocked the amphetamine-evoked rotation. No spontaneous catecholamine release could be detected from the implanted chromaffin cells by in vivo electrochemistry, while treatment with amphetamine or nicotine did evoke a release. The results suggest that the functional effects of such intrastriatal grafts of chromaffin cells, reported in previous studies, cannot be explained by the secretion from the grafted cells of catecholamines into the denervated striatum. On the other hand the results obtained following the pharmacological stimulation of these cells indicate that adrenal grafts can, under suitable conditions, influence the functioning of the host nervous system.
本实验的目的是测试植入大鼠纹状体的肾上腺嗜铬细胞是否能通过释放儿茶酚胺发挥功能作用。将从牛肾上腺髓质获得的细胞悬液单侧植入纹状体。预先广泛破坏纹状体多巴胺能输入，以排除内源性多巴胺能神经元对纹状体重新支配的可能性。通过测量药物诱导的旋转来测试植入物的功能影响，随后通过体内电化学方法在同一动物中测量儿茶酚胺释放。体内实验结束时进行的免疫组织化学分析显示，移植存活率差异很大。存活的嗜铬细胞保持其内分泌形态，未检测到宿主纹状体的重新支配。损伤后由阿扑吗啡（0.1 mg/kg，皮下注射）或苯丙胺（5.0 mg/kg，腹腔注射）诱发的动物旋转在移植后不受影响，即使回收了大量移植组织。另一方面，尼古丁（0.5 mg/kg，皮下注射）在携带移植组织的动物中诱发强烈的对侧旋转反应。这种反应不能归因于外周释放并通过植入手术打开的血脑屏障进入神经系统的物质的中枢作用，因为在植入其他外周内分泌组织（即垂体）的动物中未发现这种反应。尼古丁的作用不受阿片拮抗剂纳洛酮（2.5 mg/kg，10分钟）或多巴胺受体阻滞剂匹莫齐特（0.5 mg/kg，1小时）预处理动物的阻断，尽管后者预处理可阻断苯丙胺诱发的旋转。通过体内电化学方法未检测到植入的嗜铬细胞有自发的儿茶酚胺释放，而苯丙胺或尼古丁处理确实诱发了释放。结果表明，先前研究中报道的这种纹状体内嗜铬细胞移植的功能作用不能用移植细胞向去神经纹状体分泌儿茶酚胺来解释。另一方面，对这些细胞进行药理刺激后获得的结果表明，肾上腺移植在合适的条件下可以影响宿主神经系统的功能。
