NGF PREVENTS FURTHER ATROPHY OF CHOLINERGIC CELLS OF THE NUCLEUS BASALIS DUE TO CORTICAL INFARCTION IN ADULT POST-HYPOTHYROID RATS BUT DOESNOT RESTORE CELL-SIZE COMPARED TO EUTHROID RATS

We have tested the hypotheses that nerve growth factor treatment in ad ult post-hypothyroid rats can: (1) restore cross-sectional area of cho linergic cells of the nucleus basalis and (2) prevent further atrophy of these neurons following cortical infaction. In addition, we assesse d the expression of p75(NGFR) and p140(trkA) mRNAs in the nucleus basa lis cells of post-hypothyroid rats. Rats were rendered hypothyroid by the addition of propylthiouracil to their diet beginning on embryonic day 19 until the age of month. At this time both the pups and their da ms continued to receive 0.05% propylthiouracil in their diet and the p ups were thyroidectomized. At 60 days, propylthiouracil treatment was interrupted and thyroxine levels were restored to normal by daily subc utaneous administration of physiological levels of thyroxine. Morphome tric analysis identified atrophied nucleus basalis magnocellularis cho linergic cells at two ages, days 75 and 105, identified by in situ hyb ridization for p75(NGFR) and p140(trkA) mRNAs in methylene blue staine d cells (day 75) and choline acetyltransferase immunostaining (day 105 ). The mean number of silver grains (pixels) per mu m(2) (mean +/- S.E .M.) of cell body cross-sectional area for p75(NGFR) mRNA in the nucle us basalis magnocellularis of euthyroid rats was 3.43 +/- 0.89, which was not statistically different from post-hypothyroid animals (4.02 +/ - 1.07). A similar finding was noted for p140(trkA) mRNA: mean number of grains in the euthyroid group was 5.54 +/- 0.96 and was not statist ically different from the post-hypothyroid group (6.32 +/- 1.45). Nerv e growth factor treatment in adulthood (between days 75 and 82) did no t restore cross-sectional area from early thyroid deprivation. However , it prevented further atrophy of nucleus basalis magnocellulars neuro ns following cortical devascularization inflicted in adulthood (day 75 ). Copyright (C) 1996 Elsevier Science B.V.