Temporal changes in PO and MBP gene expression after crush-injury of the adult peripheral nerve.

The crush-injured sciatic nerve provides a model to study Schwann cell regulation of myelin gene expression during the process of demyelination and remyelination. In order to investigate the possible transcriptional regulation of myelin gene expression, the quantity, quality and translational efficiency of PO (the major myelin glycoprotein) and MBP (the myelin basic proteins) coding messages were investigated as a function of time following crush-injury of the adult rat sciatic nerve. Northern blot analysis indicated that the size of the PO and MBP transcripts remain unchanged in the distal segments of crushed sciatic nerves at 1, 2, 4, 7, 10, 14 and 21 days after crush-injury. Dot-blot analysis showed a sharp drop in levels of PO and MBP coding transcripts 1 day after crush-injury with the lowest steady-state levels at 4-7 days. Message levels were found to increase after 7 days, the highest increase in levels of message was found to be between 10 and 14 days. The highest steady-state level of both transcripts was observed at 21 days. In vitro translation and immunoprecipitation of PO-translated products from various stages of crush-injury also indicated this trend. The pattern of gene expression of PO- and MBP-coding transcripts parallel each other and follow the pattern of demyelination and remyelination. The results are also consistent with our previous interpretation which suggests that PO and MBP gene expression is regulated at the level of transcription and that these two genes might be coordinately expressed. Western blot analysis of PO protein from these stages revealed a similar decrease and then increase in the levels of the protein.(ABSTRACT TRUNCATED AT 250 WORDS)