We have tested the hypotheses that
nerve growth factor treatment in adult post-hypothyroid rats can: (1) restore cross-sectional area of
cholinergic cells of the nucleus basalis and (2) prevent further
atrophy of these neurons following cortical
infarction. In addition, we assessed the expression of p75NGFR and p140trkA mRNAs in the nucleus basalis 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 1 month. At this time both the pups and their dams continued to receive 0.05%
propylthiouracil in their diet and the pups were thyroidectomized. At 60 days,
propylthiouracil treatment was interrupted and
thyroxine levels were restored to normal by daily subcutaneous administration of physiological levels of
thyroxine. Morphometric analysis identified atrophied nucleus basalis magnocellularis
cholinergic cells at two ages, days 75 and 105, identified by in situ hybridization for p75NGFR and p140trkA mRNAs in
methylene blue stained cells (day 75) and
choline acetyltransferase immunostaining (day 105). The mean number of
silver grains (pixels) per microns2 (mean +/- S.E.M.) of cell body cross-sectional area for p75NGFR
mRNA in the nucleus 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 p140trkA
mRNA: mean number of grains in the euthyroid group was 5.54 +/- 0.96 and was not statistically different from the post-hypothyroid group (6.32 +/- 1.45).
Nerve growth factor treatment in adulthood (between days 75 and 82) did not restore cross-sectional area from early thyroid deprivation. However, it prevented further
atrophy of nucleus basalis magnocellularis neurons following cortical devascularization inflicted in adulthood (day 75).