Effect of peripheral axotomy on gene expression of NIDD in rat neural tissues

Peripheral nerve lesion-induced production of neuronal nitric oxide synthase (nNOS) was implicated to influence a range of postaxotomy processes necessary for neuronal survival and nerve regeneration (Zochodne et al., Neuroscience, 91:1515-1527, 1999; Keilhoff et al., J. Chem. Neuroanat., 24:181-187, 2002, Nitric Oxide, 10:101-111, 2004). Protein-protein interactions represent an important mechanism in the control of NOS spatial distribution or activity (Alderton et al., Biochem. J., 357:593-615, 2001; Dedio et al., FASEB J., 15:79-89, 2001; Zimmermann et al., Proc. Natl. Acad. Sci., 99:17167-17172, 2002). As one of the nNOS-binding proteins, nNOS-interacting DHHC domain-containing protein with dendritic mRNA (NIDD) has recently been identified to increase nNOS enzyme activity by targeting nNOS to the synaptic plasma membrane in a postsynaptic density protein 95/discs-large/zona occlusens-1 domain dependent manner (Saitoh et al., J. Biol. Chem., 279:29461-29468, 2004). In this paper, we established a rat model with peripheral axotomy to investigate the gene expression patterns of NIDD in neural tissues using TaqMan quantitative real-time polymerase chain reaction and in situ hybridization combined with immunofluorescence. It revealed that NIDD mRNA was upregulated after sciatic nerve transection with the similar expressing styles as that of the nNOS in the injured nerves, corresponding dorsal root ganglia, and lumbar spinal cord. These findings imply that NIDD may be involved in the different pathological conditions including nerve regeneration, neuron loss or survival, and even pain process, possibly via regulating the enzyme nNOS activity.