Abstract
The activities of various presynaptic cholinergic parameters were determined in hippocampal synaptosomes of rats 29 weeks after intracerebroventricular injection of ethylcholine aziridinium (AF64A) (3 nmol/2 μl/side) or vehicle (saline). Synaptosomes were preloaded with [ 3H]choline ([ 3H]Ch), treated with diisopropyl fluorophosphate to inhibit cholinesterase activity and then were assayed for their content of [ 3H]Ch and [ 3H]acetylcholine ([ 3H]ACh) and for their ability to synthesize and release [ 3H]ACh. In synaptosomes from AF64A-treated rats compared with synaptosomes from vehicle-treated rats we observed that: (i) specific uptake of [ 3H]ACh was reduced to 60% of control; (ii) residing [ 3H]ACh levels were 43% of control while residing [ 3H]Ch levels were 72% of control; (iii) basal and K +-induced [ 3H]ACh release were 77% and 73% of control, respectively; (iv) high K +-induced synthesis of [ 3H]ACh was only 9% of control; (v) but, choline acetyltransferase activity remained relatively high, being 80% of control. These results suggest that AF64A-induced cholinergic hypofunction is expressed by both loss of some cholinergic neurons and impairment in the functioning of the spared neurons.
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