Graybiel A M, Ohta K, Roffler-Tarlov S
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
J Neurosci. 1990 Mar;10(3):720-33. doi: 10.1523/JNEUROSCI.10-03-00720.1990.
In mice carrying the autosomal recessive gene weaver, there is a massive postnatal loss of dopamine in the caudoputamen, the target of the nigrostriatal system, with relative (though not complete) preservation of dopamine in the ventral striatum, a target of the mesolimbic system. There is concomitant death of catecholaminergic neurons in the substantia nigra, with much less cell death in the limbic midbrain area. In the study reported here, we have reexamined the mesostriatal system of weaver mice by means of tyrosine hydroxylase (TH) immunohistochemistry in order to determine the local architecture of the defect within the striatum and substantia nigra. For the dorsal striatum, the most striking finding was the appearance in the weaver caudoputamen of small pockets of especially weak immunostaining within a larger dorsal zone of generally reduced TH-positive neuropil. These pockets were identified as striosomes by calbindin28k and met-enkephalin immunohistochemistry carried out on adjacent sections. In dorsal, central, and caudal sectors of the caudoputamen, there was also more generalized depletion of TH-immunoreactive neuropil. In the mid-brains of the mutants, the patterns of loss of TH-positive neurons appeared to correspond to these distributions of reduced immunostaining in the striatum. In the substantia nigra pars compacta, ventrally situated TH-positive neurons were especially affected, suggesting preferential depletion of TH-positive neurons projecting to striosomes. In addition, there was a central sector of nearly complete loss of TH-positive neurons in the substantia nigra para compacta and a marked depletion of TH-positive neurons in cell group A8 that, together, may have accounted for the diminution of TH-positive innervation of the striatal matrix. We conclude that the effects of the weaver gene discriminate among mesostriatal subsystems not only according to the regional affiliations of these subsystems within the dorsal and ventral striatum, but also according to the preferential association of the subsystems for the striosomal and matrical compartments of the caudoputamen. The depletion of TH-positive innervation was not confined to the dorsal striatum proper. The defect extended into the adjoining nucleus accumbens, where it appeared to affect the lateral "core" division, and included also a lateral part of the olfactory tubercle. Thus, as in the dorsal striatum, the defect in the TH-positive innervation of the ventral striatum closely follows the local architecture of this striatal region. Neuronal loss in the ventral tegmental area was not evident on qualitative analysis, but at the border between lateral cell group A 10 and medial cell group A9 there was obvious loss of immunostained neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
在携带常染色体隐性基因weaver的小鼠中，黑质纹状体系统的靶标——尾壳核中，多巴胺在出生后大量减少，而中脑边缘系统的靶标——腹侧纹状体中的多巴胺则相对（尽管并非完全）得以保留。黑质中的儿茶酚胺能神经元随之死亡，而边缘中脑区域的细胞死亡则少得多。在本文报道的研究中，我们通过酪氨酸羟化酶（TH）免疫组织化学方法重新检查了weaver小鼠的中脑纹状体系统，以确定纹状体和黑质内缺陷的局部结构。对于背侧纹状体，最显著的发现是，在weaver小鼠的尾壳核中，在TH阳性神经纤维普遍减少的较大背侧区域内，出现了一些免疫染色特别弱的小区域。通过对相邻切片进行钙结合蛋白28k和甲硫氨酸脑啡肽免疫组织化学，这些区域被确定为纹状体小体。在尾壳核的背侧、中央和尾侧部分，TH免疫反应性神经纤维也有更广泛的减少。在突变小鼠的中脑中，TH阳性神经元的丧失模式似乎与纹状体中免疫染色减少的这些分布相对应。在黑质致密部，位于腹侧的TH阳性神经元受到的影响尤为明显，这表明投射到纹状体小体的TH阳性神经元优先减少。此外，黑质旁致密部有一个几乎完全丧失TH阳性神经元的中央区域，以及A8细胞群中TH阳性神经元明显减少，这两者加在一起，可能解释了纹状体基质中TH阳性神经支配的减少。我们得出结论，weaver基因的影响不仅根据这些子系统在背侧和腹侧纹状体内的区域归属来区分中脑纹状体子系统，还根据这些子系统与尾壳核的纹状体小体和基质区室的优先关联来区分。TH阳性神经支配的减少并不局限于背侧纹状体本身。缺陷延伸到相邻的伏隔核，似乎影响到外侧的“核心”部分，还包括嗅结节的外侧部分。因此，与背侧纹状体一样，腹侧纹状体中TH阳性神经支配的缺陷紧密跟随该纹状体区域的局部结构。定性分析未发现腹侧被盖区有明显的神经元丢失，但在外侧A10细胞群和内侧A9细胞群之间的边界处，有明显的免疫染色神经元丢失。（摘要截断于400字）
