THE EFFECTS OF AN RNA-SYNTHESIS INHIBITOR ON THE SURVIVAL AND REGENERATION OF RAT MOTONEURONS INJURED AT BIRTH

This preliminary study aimed to test the proposal that neuronal death is triggered by expression of specific genes. hi rat pups, the sciatic nerve was injured unilaterally on the first day after birth and actin omycin Di an RNA synthesis inhibitor, was administered 3 days later in a lower and higher dose to rat pups just prior to onset of motoneuron e death induced by the lesion. Four weeks later, sciatic motoneurones from operated and contralateral pools were counted and their size meas ured. Significantly fewer motoneurones (16.7% +/- 2.9 SD) survived whe n the animals were treated with a lower dose of the inhibitor compared to saline treated controls (36.6% +/- 12.7 SD). Experiments recording tension generated in soleus muscle in response to sciatic nerve stimu lation, at different ages following nerve crush, suggested that the tr eatment with the RNA synthesis inhibitor may have delayed regeneration of motor axons back to the muscle. However, survival of motoneurones after treatment with the higher dose did not differ significantly from controls (27.5% +/- 1.3 SD. Nevertheless, the higher dose significant ly reduced growth of motoneurones after 4 weeks. Therefore, the higher dose, although impeding normal development of motoneurones, is less n eurotoxic than a lower dose. This suggests that a balancing of conflic ting effects may have occurred. The neurodegenerative effects of delay ed reinnervation induced by RNA synthesis inhibition may be balanced b y some neuroprotective effects at a higher dose. More extensive studie s are required to validate these pilot findings. (C) 1996 Academic Pre ss Limited.