Marked increase in β-tubulin mRNA expression during regeneration of axotomized retinal ganglion cells in adult mammals

Abstract

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 β-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 β-tubulin, NF-M, and GAPDH mRNA levels decreased and remained low during the 1 month studied. In these retinas β-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 β-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; β-tubulin mRNA levels in non-regenerating RGCs of the same retinas averaged 63% of controls. We suggest that interactions of RGC axons and components of the grafts' non-neuronal environment play a key role in the over fourfold differences in β-tubulin mRNA levels observed between injured and regenerating RGCs. Copyright © 1993 Society for Neuroscience.