Higo Noriyuki, Nishimura Yukio, Murata Yumi, Oishi Takao, Yoshino-Saito Kimika, Takahashi Masahito, Tsuboi Fumiharu, Isa Tadashi
Systems Neuroscience Group, Neuroscience Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
J Comp Neurol. 2009 Oct 20;516(6):493-506. doi: 10.1002/cne.22121.
To investigate the neural basis for functional recovery of the cerebral cortex following spinal cord injury, we measured the expression of growth-associated protein 43 (GAP-43), which is involved in the process of synaptic sprouting. We determined the GAP-43 mRNA expression levels in the sensorimotor cortical areas of macaque monkeys with a unilateral lesion of the lateral corticospinal tract (l-CST) at the C4/C5 level of the cervical cord and compared them with the levels in the corresponding regions of intact monkeys. Lesioned monkeys recovered finger dexterity during the first months after surgery, and the GAP-43 mRNA levels increased in layers II-III in primary motor areas (M1), bilaterally. Double-labeling analysis of the lesioned monkeys showed that GAP-43 mRNA was expressed strongly in excitatory neurons but only rarely in inhibitory interneurons. Expression also increased in the medium-sized (area, 500-1,000 microm(2)) and large pyramidal cells (area, >1,000 microm(2)) in layer V of the bilateral M1. The increased expression of GAP-43 mRNA in the M1 contralateral to the lesion was more prominent during the early recovery stage than during the late recovery stage. In addition, GAP-43 mRNA increased in layers II-III of both the contralesional ventral premotor area and the primary somatosensory area. These results suggest that GAP-43 is involved in time-dependent and brain region-specific plastic changes after l-CST lesioning. The expression patterns imply that plastic changes occur not only in M1 but also in the broad associative cortical network, including the ventral premotor and primary sensory areas.
为了研究脊髓损伤后大脑皮质功能恢复的神经基础，我们测量了生长相关蛋白43（GAP - 43）的表达，该蛋白参与突触萌发过程。我们测定了颈髓C4/C5水平单侧皮质脊髓侧束（l - CST）损伤的猕猴感觉运动皮质区域中GAP - 43 mRNA的表达水平，并将其与完整猕猴相应区域的水平进行比较。损伤的猕猴在手术后的头几个月恢复了手指灵活性，并且双侧初级运动区（M1）的II - III层中GAP - 43 mRNA水平升高。对损伤猕猴的双标分析表明，GAP - 43 mRNA在兴奋性神经元中强烈表达，但在抑制性中间神经元中很少表达。双侧M1的V层中型（面积，500 - 1,000平方微米）和大型锥体细胞（面积，>1,000平方微米）中的表达也增加。损伤对侧M1中GAP - 43 mRNA表达的增加在早期恢复阶段比晚期恢复阶段更明显。此外，损伤对侧腹侧运动前区和初级体感区的II - III层中GAP - 43 mRNA也增加。这些结果表明，GAP - 43参与了l - CST损伤后的时间依赖性和脑区特异性可塑性变化。表达模式表明，可塑性变化不仅发生在M1中，也发生在包括腹侧运动前区和初级感觉区在内的广泛联合皮质网络中。
