Heath P R, Chessell I P, Sanders M W, Francis P T, Bowen D M, Pearson R C
Department of Biomedical Science, University of Sheffield, United Kingdom.
Exp Neurol. 1997 Sep;147(1):192-203. doi: 10.1006/exnr.1997.6586.
We have examined the time course of neurodegeneration in subcortical nuclei and other cortical areas known to project to the rat parietal cortex, following unilateral injection of the suicide transport agent, volkensin, into the cortex of one side. Degenerating neurons, visualized by Gallyas silver staining were most prominent 21 days after injection. At this time darkly staining neurons were present in nuclei and areas known to project to the injected cortical area but not in other sites. Affected subcortical nuclei included the ipsilateral ventral thalamus and intralaminar nuclei, the basal nucleus of Meynert and claustrum of the same side, and the dorsal median raphé nucleus of both sides. Within the cortex degenerating pyramidal neurons were visible in the contralateral parietal cortex and in the frontal cortex of the same side. The distribution of degenerating cells is in agreement with the conclusion that only neurons projecting to the injection site were affected. The time course of the appearance of the degeneration and its distribution are in keeping with axonal transport rather than spread by diffusion of the toxin. Neuronal counts in Nissl-stained sections of the contralateral SMI confirmed significant neuronal loss 28 days after injection. In situ hybridization studies using an oligonucleotide probe directed against GAD mRNA and counts of GAD mRNA-positive neurons in the contralateral cortex confirmed that this population of cortical interneurons, which do not project to the injection site, were unaffected.
我们研究了在单侧将自杀性转运剂沃肯辛注入一侧大鼠皮层后,已知投射至大鼠顶叶皮层的皮层下核团及其他皮层区域的神经退行性变的时间进程。通过加利亚斯银染色观察到的变性神经元在注射后21天最为明显。此时,在已知投射至注射皮层区域的核团和区域中存在深色染色的神经元,而在其他部位则没有。受影响的皮层下核团包括同侧腹侧丘脑和板内核、同侧的迈内特基底核和屏状核,以及双侧的背正中缝核。在皮层内,对侧顶叶皮层和同侧额叶皮层可见变性的锥体细胞。变性细胞的分布与仅投射至注射部位的神经元受到影响这一结论相符。变性出现的时间进程及其分布与轴突运输一致,而非毒素扩散所致。注射后28天,对侧半薄切片尼氏染色的神经元计数证实存在明显的神经元丢失。使用针对谷氨酸脱羧酶(GAD)mRNA的寡核苷酸探针进行的原位杂交研究以及对侧皮层中GAD mRNA阳性神经元的计数证实,这群不投射至注射部位的皮层中间神经元未受影响。