McKerracher L, Essagian C, Aguayo A J
Centre for Research in Neuroscience, Montreal General Hospital Research Institute, Quebec, Canada.
J Neurosci. 1993 Dec;13(12):5294-300. doi: 10.1523/JNEUROSCI.13-12-05294.1993.
Changes in gene expression were investigated in axotomized CNS neurons under conditions that inhibit or permit regrowth of their damaged axons. Levels of mRNA encoding beta-tubulin, the 150 kDa neurofilament subunit (NF-M), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were examined by quantitative in situ hybridization of adult rat retinal ganglion cells (RGCs) after axotomy in the optic nerve or during regeneration in a peripheral nerve (PN) graft. Soon after optic nerve section beta-tubulin, NF-M, and GAPDH mRNA levels decreased and remained low during the 1 month studied. In these retinas beta-tubulin mRNA fell to approximately 50% of normal controls. However, in the PN-grafted retinas, where approximately 20% of the surviving axotomized RGCs regenerate their axons, there were "hot spots" of beta-tubulin mRNAs where neuronal levels were nearly 300% higher than in controls. By retrograde neuronal labeling these hot spots were shown to correspond to the injured RGCs that regrew their axons into the PN graft; beta-tubulin mRNA levels in nonregenerating RGCs of the same retinas averaged 63% of controls. We suggest that interactions of RBC axons and components of the grafts' non-neuronal environment play a key role in the over fourfold differences in beta-tubulin mRNA levels observed between injured and regenerating RGCs.
在抑制或允许受损轴突再生的条件下，研究了轴突切断的中枢神经系统神经元中的基因表达变化。通过对成年大鼠视神经切断后或周围神经（PN）移植再生过程中的视网膜神经节细胞（RGCs）进行定量原位杂交，检测了编码β-微管蛋白、150 kDa神经丝亚基（NF-M）和甘油醛-3-磷酸脱氢酶（GAPDH）的mRNA水平。视神经切断后不久，β-微管蛋白、NF-M和GAPDH的mRNA水平下降，并在研究的1个月内保持较低水平。在这些视网膜中，β-微管蛋白mRNA降至正常对照的约50%。然而，在PN移植的视网膜中，约20%存活的轴突切断的RGCs再生了它们的轴突，存在β-微管蛋白mRNA的“热点”，其中神经元水平比对照高出近300%。通过逆行神经元标记，这些热点被证明对应于其轴突再生进入PN移植的受损RGCs；同一视网膜中未再生的RGCs中的β-微管蛋白mRNA水平平均为对照的63%。我们认为，RBC轴突与移植的非神经元环境成分之间的相互作用在受伤和再生的RGCs之间观察到的β-微管蛋白mRNA水平四倍以上的差异中起关键作用。
