The long-range goal of this project is to supplement light and electron microscopic studies with in situ nucleic acid hybridization techniques and immunocytochemical methods to investigate cellular mechanisms of myelin formation, breakdown and regeneration. Current studies and major findings are: (1) Development expression of mRNA encoding for P glycoprotein in postnatal rat peripheral nervous tissue demonstrated by in situ hybridization. Aldehyde-fixed light microscopic vibratome and semithin sections of trigeminal nerves and ganglia from developing and adult rats were treated et al., (1987). Reaction product that localized P mRNA was detected by light and electron microscopy at 2d in perinuclear cytoplasmic regions of myelin-forming Schwann cells that were enriched in granular endoplasmic reticulum. It also was found in internodal and paranodal regions, often next to uter margins of developing myelin sheaths. The number of cells containing reaction product and the amount per myelin-forming Schwann cell was highest at 7d and 15d, was less at 30d and still less (but detectable) in the adult. At 2d and 7d, reaction product was also present in the perinuclear cytoplasm of Schwann cells that surround neurons and do not ever form myelin in vivo. These results suggests that all Schwann cells can transcribe P message and transport it into the cytoplasm. Presumably low levels are present there unless myelination occurs. (2) Myelin regeneration in nerves of senescent mice, Kazui and Fujisawa (1988) have shown that more nerve fiber lesions are present in sciatic nerves of aging than young adult rats; also more lesions are found proximally than distally. In LENP, these findings have been confirmed in sciatic nerves of 20-30 month old mice. Preliminary electron microscopic findings also show that myelin regeneration is abnormal; more mice are being studied. Mechanisms of abnormal regeneration will be investigated.
