Age-Related Loss of GABA-Positive and GABA-Negative Neurons in Neocortical Transplants

The numerical density of GABA immunopositive and GABA immunonegative neurons was quantitatively determined in 0, 12, 30 and 90 day-old neocortical transplants, derived from E17 rat embryos and transplanted into adult hosts. It was found that the original, very high neuronal density in the fetal transplant declined steadily after transplantation to the somatosensory cortex of adult rat. The decline in numerical density of GABA-positive neurons, however, was disproportionately larger than that of GABA-negative nerve cells: At 90 days the proportion of GABA-positive cells was 2.3% (in contrast to the 11.8% in the adult host cortex). The density of GABA-negative neurons, on the other hand, remained slightly higher than comparable values in the control cortex. The decline in density Of GABA-positive neurons was continuous until the 90th post-transplantation day, while final, close to normal density values of GABA-negative nerve cells were already reached in 30 day-old grafts, with no significant change afterwards.

Fetal Transplant-Induced Restoration of Spatial Memory in Rats with Lesions of the Nucleus Basalis of Meynert

Bilateral lesions of the nucleus basalis of Meynert (nbM) in rats produced mnemonic deficits when subjects were tested on tests of spatial memory over a period of 3 to 7.5 months postoperatively. The transplantation of cholinergic-rich, fetal ventral forebrain tissue to either two or four frontoparietal cortical sites normalized performance on the spatial memory tasks. However, which transplant condition yielded recovery depended upon the nature of the task and/or posttransplantation interval. When assessed 8 months following transplant surgery, cortical choline acetyltransferase and acetylcholinesterase activity levels in both transplant groups were comparable to those values found in sham-operated animals. These data indicate that fetal transplants can reverse the mnemonic deficits and restore cortical cholinergic neurochemical activity to near-normal levels in rats with nbM lesions.