IPP isomerase, an enzyme of mevalonate pathway, is preferentially expressed in postnatal cortical neurons and induced after nerve transection

To understand the molecular mechanisms underlying the developmental process es of the cerebral cortex, we screened genes whose mRNA expression was up-r egulated in neonatal in the rat cortex to a greater extent than in adult by differential display and obtained five genes. Among these genes, we focuse d on pyrophosphate (isopentenyl diphosphate, dimethylallyl diphosphate: IPP ) isomerase gene, the product of which is known as an enzyme of the mevalon ate pathway. Rat IPP isomerase was recently cloned and the gene expression was shown to be dependent on the activation of the mevalonate pathway. its expression and roles in the brain, however, have not been investigated hith erto. In the present study, Northern blots and in situ hybridization analys is showed that at embryonic stage weak signals for IPP mRNA were diffusely detected in the CNS, and the signal in the cortex became intense at postnat al day 1 and maximized in almost all neurons of all layers at postnatal day 7 with a subsequent reduction. At 8 weeks, the expression of IPP isomerase mRNA in neurons decreased, while it was detected in the oligodendrocytes i n the regions containing abundant nerve fibers. These findings suggested th at IPP isomerase contributes to postnatal neuronal maturation and myelinati on. We also demonstrated that IPP isomerase mRNA is induced after nerve axo tomy, which suggests a relationship between neuronal regeneration and IPP i somerase. Taken together, these results suggest that elevation of IPP isome rase mRNA levels in neurons contributes to construction of nerve fibers bot h during the postnatal period in the cortex and their regeneration. (C) 199 9 Elsevier Science B.V, All rights reserved.