Date I, Felten S Y, Olschowka J A, Felten D L
Department of Neurobiology & Anatomy, University of Rochester School of Medicine, New York 14642.
Exp Neurol. 1990 Mar;107(3):197-207. doi: 10.1016/0014-4886(90)90136-g.
Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages the dopaminergic (DA) nigrostriatal system in C57BL/6 mice. We have investigated the effect of MPTP neurotoxicity and subsequent adrenal medullary grafts into the striatum of young (2-3 months) and aging (12 months) mice. MPTP treatment (4 X 20 mg/kg ip given 3 or 12 h apart in young mice and 12 h apart in aging mice) resulted in 80-90% depletion of striatal DA and virtual disappearance of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers in both young and aging mice 1 week following treatment. Only partial recovery of TH-IR fibers was seen 5 weeks after MPTP treatment in young mice, while virtually no recovery was seen in aging mice. Adrenal medullary minced pieces were grafted into the striatum of young and aging mice 1 week after MPTP treatment. In young mice, dense TH-IR fibers were observed in the striatum on the grafted side 4 weeks later, far denser than those in sham-operated striatum. Although this staining was most prominent around the grafts, many TH-IR fibers also were found in the ventral striatum close to the nucleus accumbens. No such increase in TH-IR fibers was found on the nongrafted side. DA concentration on the grafted side recovered to 45% of the control level. In aging mice receiving similar grafts, TH-IR fibers also were observed in the grafted striatum, but were less dense and more restricted around the site of the graft compared with young mice. DA concentration on the grafted side was 29% of the control level. We conclude that the MPTP-depleted nigrostriatal DA system in aging mouse brain can recover partially following adrenal medullary grafts, but the degree of recovery is more limited compared with that in young brain.
向C57BL/6小鼠全身注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会损害多巴胺能（DA）黑质纹状体系统。我们研究了MPTP神经毒性以及随后将肾上腺髓质移植到年轻（2 - 3个月）和老龄（12个月）小鼠纹状体中的效果。MPTP处理（年轻小鼠每隔3或12小时腹腔注射4×20 mg/kg，老龄小鼠每隔12小时注射）导致处理后1周，年轻和老龄小鼠纹状体中DA耗竭80 - 90%，酪氨酸羟化酶（TH）免疫反应性（IR）纤维几乎消失。MPTP处理5周后，年轻小鼠的TH - IR纤维仅部分恢复，而老龄小鼠几乎未见恢复。MPTP处理1周后，将肾上腺髓质碎块移植到年轻和老龄小鼠的纹状体中。4周后，在年轻小鼠移植侧的纹状体中观察到密集的TH - IR纤维，比假手术纹状体中的纤维密集得多。尽管这种染色在移植周围最为明显，但在靠近伏隔核的腹侧纹状体中也发现了许多TH - IR纤维。未移植侧未发现TH - IR纤维有这种增加。移植侧的DA浓度恢复到对照水平的45%。在接受类似移植的老龄小鼠中，移植的纹状体中也观察到了TH - IR纤维，但与年轻小鼠相比，其密度较低且更局限于移植部位周围。移植侧的DA浓度为对照水平的29%。我们得出结论，老龄小鼠脑中MPTP耗竭的黑质纹状体DA系统在肾上腺髓质移植后可部分恢复，但与年轻脑相比，恢复程度更有限。
