OLIGODENDROCYTE SURVIVAL AND FUNCTION IN THE LONG-LIVED STRAIN OF THEMYELIN-DEFICIENT RAT

This study has examined cellular and molecular aspects of glial cell f unction in a newly described long-lived myelin deficient rat mutant. I n contrast to the shorter-lived mutants which died at 25-30 days, the longer lived mutant rats lived to 75-80 days of age. Despite living lo nger, these mutants had a similar frequency of seizures to their young er counterparts. In the spinal cord and optic nerves of the older muta nts, myelinated fibres in similar numbers to those seen in the younger myelin deficient rats were present. However, the total glial cell num bers were markedly reduced with few remaining normal appearing oligode ndrocytes, and very few microglia compared to the younger mutants. In addition, little or no cell death or division was seen in the longer-l ived rats. However, there was some evidence of ongoing myelination and the persistence of immature oligodendrocytes or their progenitors in the older mutant. There was some continued myelin gene expression, alt hough this was at much reduced levels compared to normal, with proteol ipid protein and myelin basic protein being most affected. In situ hyb ridization analysis for proteolipid protein mRNA showed that few prote olipid protein expressing oligodendrocytes remained in the 70-80-day-o ld mutant. Polymerase chain reaction analysis of exon 3 of the long-li ved mutant revealed the same point mutation as described in the younge r myelin deficient rat.