Dimethylarginine dimethylaminohydrolase (DDAH) as a nerve-injury-associated molecule: mRNA localization in the rat brain and its coincident up-regulation with neuronal NO synthase (nNOS) in axotomized motoneurons

As part of a project to identify genes up-regulated by injury of the motor neuron, a clone encoding dimethylarginine dimethylaminohydrolase (DDAH) was isolated. This enzyme is known to metabolize methylarginines, which are en dogenous inhibitors of NOS activity. DDAH may therefore contribute to the c ontrol of NO synthesis. The present study demonstrated that both DDAH and n NOS mRNAs are up-regulated after axotomy in injured hypoglossal motor neuro ns. The profile of DDAH mRNA up-regulation in the injured hypoglossal motor neurons paralleled that of NADPH diaphorase staining, While the expression of both DDAH and nNOS was upregulated in motor neurons following nerve inj ury, the normal distribution of DDAH and nNOS mRNAs in the noninjured centr al nervous system were distinctly different. We speculate that both genes a re involved in the upregulation of NO production following nerve transectio n, although the role of NO in the process of nerve regeneration is so far u nknown.