Pasinetti G M, Lerner S P, Johnson S A, Morgan D G, Telford N A, Finch C E
Andrus Gerontology Center, University of Southern California, Los Angeles 90089-0191.
Brain Res Mol Brain Res. 1989 May;5(3):203-9. doi: 10.1016/0169-328x(89)90036-3.
Long-term effects of lesions were analyzed in terms of gene expression. Nine months after unilateral 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra pars compacta (s. nigra), the remaining dopaminergic (DAergic) neurons (tyrosine hydroxylase (TH) cells determined by immunocytochemistry (ICC] on the lesioned side were atrophic with smaller nucleoli. By in situ hybridization, the DAergic neurons on the lesioned side had a 50% smaller TH-mRNA concentration than on the contralateral non-lesioned side. However, beta-tubulin mRNA concentration in DAergic neurons was unaffected by the lesion. The lesions did not alter TH-mRNA concentration in the contralateral non-lesioned side by comparison with unoperated controls. We propose that chronic lesions have long-term effects on gene expression because of damage sustained during compensatory hyperactivity after the lesion, or because of decreased trophic support from other neurons.
从基因表达方面分析了损伤的长期影响。在黑质致密部(s. nigra)单侧注射6-羟基多巴胺(6-OHDA)损伤九个月后,损伤侧通过免疫细胞化学(ICC)确定的剩余多巴胺能(DAergic)神经元(酪氨酸羟化酶(TH)细胞)萎缩,核仁较小。通过原位杂交,损伤侧的DAergic神经元TH-mRNA浓度比未损伤的对侧低50%。然而,DAergic神经元中的β-微管蛋白mRNA浓度不受损伤影响。与未手术的对照相比,损伤并未改变对侧未损伤侧的TH-mRNA浓度。我们认为,慢性损伤对基因表达有长期影响,这是由于损伤后代偿性活动亢进期间持续的损伤,或由于其他神经元的营养支持减少。