Le Marec N, Hébert C, Botez M I, Botez-Marquard T, Marchand L, Reader T A
Centre for Research in Neurological Sciences, Department of Physiology, Faculty of Medicine, University of Montréal, CHUM--Hôtel-Dieu Hospital, Québec, Canada.
Brain Res Bull. 1999 Jan 15;48(2):195-201. doi: 10.1016/s0361-9230(98)00164-6.
The Lurcher (Lc/+) mutant mouse is characterized by a considerable atrophy of the cerebellum due to a massive loss of cerebellar Purkinje and granule cells, as well as of neurons from the inferior olivary nucleus. In this study the effects of a therapeutic combination of amantadine, thiamine and L-tryptophan on the serotonin (5-HT) innervation was assessed in Lurcher mice by autoradiography, using [3H]citalopram to label 5-HT transporters. In wild type mice as well as in both saline-treated and drug-treated Lurcher mutants, [3H]citalopram binding remained unchanged in forebrain and brainstem regions. In the cerebellum, labelling of deep cerebellar nuclei (CBnuc) was about twofold higher than in the cortex (CBctx). In saline-treated Lurcher mutants compared to wild type mice, the densities of [3H]citalopram were 98% higher in CBctx, and 180% higher in CBnuc. In CBctx of drug-treated Lurcher mutants, transporter densities were 89% higher than in the wild type, but did not differ from the saline-treated Lurcher. In the CBnuc of the drug-treated Lurcher mutants, [3H]citalopram binding was 50% higher than in the saline-treated Lurcher group, and 320% higher than in wild type mice. The results show that 5-HT transporters, already upregulated in the CBnuc of Lurcher mutant mice, can be further increased by a pharmacological treatment, possibly altering the availability of 5-HT in some of its target areas.
蹒跚突变小鼠（Lc/+）的特征是小脑明显萎缩，这是由于小脑浦肯野细胞和颗粒细胞大量丧失，以及下橄榄核神经元丧失所致。在本研究中，通过放射自显影术，使用[3H]西酞普兰标记5-羟色胺（5-HT）转运体，评估了金刚烷胺、硫胺素和L-色氨酸的治疗组合对蹒跚小鼠5-HT神经支配的影响。在野生型小鼠以及生理盐水处理和药物处理的蹒跚突变小鼠中，[3H]西酞普兰结合在前脑和脑干区域保持不变。在小脑中，小脑深部核团（CBnuc）的标记比皮质（CBctx）高约两倍。与野生型小鼠相比，生理盐水处理的蹒跚突变小鼠中，[3H]西酞普兰在CBctx中的密度高98%，在CBnuc中高180%。在药物处理的蹒跚突变小鼠的CBctx中，转运体密度比野生型高89%，但与生理盐水处理的蹒跚小鼠没有差异。在药物处理的蹒跚突变小鼠的CBnuc中，[3H]西酞普兰结合比生理盐水处理的蹒跚小鼠组高50%，比野生型小鼠高320%。结果表明，在蹒跚突变小鼠的CBnuc中已经上调的5-HT转运体，可通过药物治疗进一步增加，这可能会改变5-HT在其某些靶区域的可用性。
