Le Marec N, Hébert C, Amdiss F, Botez M I, Reader T A
Centre de Recherche en Sciences Neurologiques, Département de Physiologie, Faculté de Médecine, Université de Montréal, Qué., Canada.
J Chem Neuroanat. 1998 Sep;15(3):155-71. doi: 10.1016/s0891-0618(98)00041-6.
The neurological mutant 'Purkinje cell degeneration' (pcd) is characterized by a primary degeneration of Purkinje cells, as well as by retrograde and secondary partial degeneration of cerebellar granule cells and inferior olivary neurons, and can be considered as an animal model of human degenerative ataxias. The serotonin (5-HT) innervation was examined in wild type and pcd mice, by quantifying 5-HT uptake sites, or transporters, using [3H]citalopram binding autoradiography. In both wild type and pcd mutants, the highest densities of 5-HT transporters were in mesencephalic and rostral pontine regions, in limbic structures, in hypothalamus and in discrete thalamic divisions, while the lowest labelling was found in cerebellum and brainstem reticular formation. In pcd mice, although [3H]citalopram labelling was higher in cerebellar cortex and deep cerebellar nuclei, when binding densities were corrected for surface area, the up-regulation of 5-HT transporters was present only in deep cerebellar nuclei. Also, higher labelling was found in nuclei raphe dorsalis and medialis, in ventral divisions of rostral neostriatum, caudal neostriatum, rostral globus pallidus, posteromedial amygdaloid nucleus, septum, olfactory tubercles, vertical limb of Broca's diagonal band, periventricular, latero-ventral and medio-ventral thalamic nuclei, medial geniculate nucleus, anterior hypothalamus and entorhinal cortex. The results indicate a relative integrity of the 5-HT innervation, but with a reorganization of serotoninergic terminals in the cerebellum, in particular in the deep cerebellar nuclei. This suggests that in progressive cerebellar degeneration, as found in the pcd mutant, the modified 5-HT system may still participate in motor functions by exerting an overall modulation of excitatory amino acid neurotransmission, but the availability of 5-HT may be altered in defined brain targets, as is the case for other spontaneous cerebellar mutants, in particular for the 'Lurcher' mutant mouse, a model of human olivopontocerebellar atrophy.
神经学突变体“浦肯野细胞变性”（pcd）的特征是浦肯野细胞原发性变性，以及小脑颗粒细胞和下橄榄核神经元的逆行性和继发性部分变性，可被视为人类退行性共济失调的动物模型。通过使用[3H]西酞普兰结合放射自显影术对5-羟色胺（5-HT）摄取位点或转运体进行定量，研究了野生型和pcd小鼠中的5-HT神经支配。在野生型和pcd突变体中，5-HT转运体的最高密度存在于中脑和脑桥前部区域、边缘结构、下丘脑以及离散的丘脑分区，而小脑和脑干网状结构中的标记最低。在pcd小鼠中，尽管小脑皮质和小脑深部核团中的[3H]西酞普兰标记较高，但在对表面积进行校正后，5-HT转运体的上调仅存在于小脑深部核团中。此外，在背侧和内侧中缝核、新纹状体前部腹侧分区、尾状核、苍白球前部、杏仁后内侧核、隔区、嗅结节、布洛卡斜带垂直支、脑室周围、丘脑外侧腹侧和内侧腹侧核、内侧膝状体核、下丘脑前部和内嗅皮质中发现了较高的标记。结果表明5-HT神经支配相对完整，但在小脑中，特别是在小脑深部核团中，5-羟色胺能终末发生了重组。这表明，在pcd突变体中发现的进行性小脑变性中，改变的5-HT系统可能仍通过对兴奋性氨基酸神经传递进行整体调节来参与运动功能，但5-HT的可用性可能在特定脑靶点中发生改变，其他自发性小脑突变体也是如此，特别是“蹒跚者”突变小鼠，一种人类橄榄桥脑小脑萎缩模型。
