Sastry S, Arendash G W
Department of Biology, University of South Florida, Tampa 33620, USA.
Neuroscience. 1995 Aug;67(3):649-66. doi: 10.1016/0306-4522(94)00618-f.
The substantia nigra and globus pallidus (two iron-rich brain areas) receive a substantial innervation from the neostriatum, a considerable amount of which is GABAergic. Because of this anatomic relationship and the finding that prevention of GABA degradation in these two areas decreases their histochemical levels of iron, GABAergic transmission/metabolism may be important in regulating brain iron levels. Therefore, the present study investigated the effects of denervation of striatal/pallidal inputs to globus pallidus/substantia nigra on iron levels and associated pathologic changes in globus pallidus/substantia nigra. Adult male Sprague-Dawley rats received unilateral ibotenic acid infusions resulting in comprehensive lesions of the entire neostriatum/globus pallidus complex, or of either the anterior neostriatum or the posterior neostriatum/globus pallidus. Animals were killed at one week or one month following surgery. Between one week and one month postlesioning, comprehensive neostriatum/globus pallidus lesions induced a progressive decrease in substantia nigra volume, as well as a progressive increase in both substantia nigra zona reticularis iron staining and substantia nigra iron concentration. By one month following neostriatum/globus pallidus lesions, a marked 73% loss of substantia nigra zona reticularis neurons occurred in association with a 65% increase in glial cell numbers within zona reticularis. Compared to comprehensive neostriatum/globus pallidus lesions at the one month postlesion time point, more restricted anterior neostriatum and posterior neostriatum/globus pallidus lesions induced a less severe atrophy of the substantia nigra, a small (anterior neostriatum lesions) to moderate (posterior neostriatum/globus pallidus lesions) increase in substantia nigra zona reticularis iron staining, and either no zona reticularis neuronal loss (anterior neostriatum lesions) or limited zona reticularis neuronal loss selectively within areas of increased iron staining. These results suggest that destruction of striatal/pallidal innervation to the substantia nigra's zona reticularis induces a disruption of zona reticularis iron homeostasis, resulting in a redistribution and/or accumulation of iron in the zona reticularis and consequent zona reticularis of the substantia nigra neurodegeneration. The results further suggest that loss or dysfunction of striatonigral/striatopallidal GABAergic neurons in several neurodegenerative diseases (including Hallervorden-Spatz syndrome, progressive supranuclear palsy, multiple system atrophy, and Parkinson's disease) may result in an increase or redistribution of nigral iron to cause loss of substantia nigra neurons.
黑质和苍白球（两个富含铁的脑区）接受来自新纹状体的大量神经支配，其中相当一部分是γ-氨基丁酸（GABA）能的。由于这种解剖学关系以及在这两个区域预防GABA降解会降低其铁的组织化学水平这一发现，GABA能传递/代谢可能在调节脑铁水平中起重要作用。因此，本研究调查了纹状体/苍白球输入至苍白球/黑质的去神经支配对苍白球/黑质中铁水平及相关病理变化的影响。成年雄性Sprague-Dawley大鼠接受单侧鹅膏蕈氨酸输注，导致整个新纹状体/苍白球复合体、或前新纹状体或后新纹状体/苍白球发生全面性损伤。动物在手术后1周或1个月处死。在损伤后1周和1个月之间，新纹状体/苍白球全面性损伤导致黑质体积逐渐减小，以及黑质网状带铁染色和黑质铁浓度逐渐增加。新纹状体/苍白球损伤后1个月，黑质网状带神经元显著丧失73%，同时网状带内胶质细胞数量增加65%。与损伤后1个月时新纹状体/苍白球全面性损伤相比，更局限的前新纹状体和后新纹状体/苍白球损伤导致黑质萎缩程度较轻，黑质网状带铁染色有小（前新纹状体损伤）到中度（后新纹状体/苍白球损伤）的增加，并且要么没有网状带神经元丧失（前新纹状体损伤），要么仅在铁染色增加区域内有局限性的网状带神经元丧失。这些结果表明，黑质网状带的纹状体/苍白球神经支配破坏会导致网状带铁稳态破坏，从而导致铁在网状带重新分布和/或蓄积，并随之导致黑质网状带神经变性。结果还进一步表明，在几种神经退行性疾病（包括Hallervorden-Spatz综合征、进行性核上性麻痹、多系统萎缩和帕金森病）中，黑质纹状体/纹状体苍白球GABA能神经元的丧失或功能障碍可能导致黑质铁增加或重新分布，从而导致黑质神经元丧失。
