Ageing changes in the transplants of fetal substantia nigra grafted to striatum of adult rat

Abstract

Fetal nigral neurons from 16 and 17 gestational days were transplanted into the intact striatum of adult rat. On different post-transplantation days (30-360 days), the structural and immunohistochemical details of the transplants were studied. The grafted neurons matured and showed phenotypical characteristics comparable to that of normal nigral neurons in adult rats until 180 days. Tyrosine hydroxylase-positive neurons were seen not only in the transplant but also in the adjacent host striatum. Tyrosine hydroxylase-positive fibres were also seen extending for a short distance into the host striatum. A large number of synapses in the transplants were of asymmetric type, containing clear round vesicles. These synapses resembled the few intrinsic type present in the normal substantia nigra. On the other hand, the predominant type 2 synapses with pleomorphic vesicles in the normal nigra were infrequently encountered in the transplants. On the 300th day, the cytoplasm of a few of the neurons showed ageing changes in the form of clear spaces, paucity of organelles especially rough endoplasmic reticulum, membrane-bound vacuoles and increase in the lipofuscin population. In addition, localized thickening of the soma and the dendrites were seen in relation to randomly distributed neurons. By 360 days, more than one quarter (26%) of the total neurons showed these changes indicating ageing. The number per unit volume of normal neurons decreased significantly when compared to the transplants on 60 and 90 days. In the substantia nigra of age-matched control, except for an increase in the lysosomal population, other ageing changes were not detectable. The neurons of intact substantia nigra of the host rat, chronologically 4-8 months older than the transplanted neurons, also appeared normal but for lipofuscin granules. The present study provides morphological evidence for rapid ageing of neurons in the long term nigral transplants. These observations raise fresh doubts regarding permanent survival of grafted neurons in the host brain. Studies so far conducted are after prior nigral lesions. Trophic factors following lesions of the host tissue may have influenced the long term survival of the transplanted neurons. On the other hand, such changes may have been missed since no detailed morphological investigations of the long term transplants have been done so far.