Bohn M C, Cupit L, Marciano F, Gash D M
Science. 1987 Aug 21;237(4817):913-6. doi: 10.1126/science.2887034.
The drug, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), depletes striatal dopamine levels in primates and certain rodents, including mice, and produces parkinsonian-like symptoms in humans and nonhuman primates. To investigate the consequences of grafting adrenal medullary tissue into the brain of a rodent model of Parkinson's disease, a piece of adult mouse adrenal medulla was grafted unilaterally into mouse striatum 1 week after MPTP treatment. This MPTP treatment resulted in the virtual disappearance of tyrosine hydroxylase-immunoreactive fibers and severely depleted striatal dopamine levels. At 2, 4, and 6 weeks after grafting, dense tyrosine hydroxylase-immunoreactive fibers were observed in the grafted striatum, while only sparse fibers were seen in the contralateral striatum. In all cases, tyrosine hydroxylase-immunoreactive fibers appeared to be from the host rather than from the grafts, which survived poorly. These observations suggest that, in mice, adrenal medullary grafts exert a neurotrophic action in the host brain to enhance recovery of dopaminergic neurons. This effect may be relevant to the symptomatic recovery in Parkinson's disease patients who have received adrenal medullary grafts.
药物1-甲基-4-苯基-1,2,5,6-四氢吡啶(MPTP)可使灵长类动物以及包括小鼠在内的某些啮齿动物纹状体中的多巴胺水平降低,并在人类和非人类灵长类动物中产生帕金森氏症样症状。为了研究将肾上腺髓质组织移植到帕金森病啮齿动物模型大脑中的后果,在MPTP治疗1周后,将一片成年小鼠肾上腺髓质单侧移植到小鼠纹状体中。这种MPTP治疗导致酪氨酸羟化酶免疫反应性纤维几乎消失,并使纹状体多巴胺水平严重降低。移植后2周、4周和6周时,在移植的纹状体中观察到密集的酪氨酸羟化酶免疫反应性纤维,而在对侧纹状体中仅观察到稀疏的纤维。在所有情况下,酪氨酸羟化酶免疫反应性纤维似乎来自宿主而非存活不佳的移植物。这些观察结果表明,在小鼠中,肾上腺髓质移植物在宿主大脑中发挥神经营养作用,以促进多巴胺能神经元的恢复。这种作用可能与接受肾上腺髓质移植的帕金森病患者的症状恢复有关。