Polymorphism of Acetylcholinesterase in Discrete Regions of the Developing Human Fetal Brain

Abstract

The molecular forms and membrane association of acetylcholinesterase (acetylcholine hydrolase, EC 3.1.1.7) and pseudocholinesterase (acylcholine acylhydrolase, EC 3.1.1.8) were determined in the presence of protease inhibitors in dissected regions of developing human fetal brain, as compared with parallel areas from mature brain. All areas contained substantial cholinesterase activities, of which acetylcholinesterase accounted for almost all the activity. Two major forms of acetylcholinesterase activity, sedimenting at 10-11S [sedimentation coefficient] and 4-5S, respectively, were detecting on sucrose gradients and possessed similar catalytic properties, as judged by their individual Km values toward [3H]acetylcholine (.apprx. 4 .times. 10-4 M). The ratio between these forms varied by up to 4-5 fold, between different areas and within particular areas at various developmental stages, but reached similar values (about 5:2) in all areas in mature brain. Acetylcholinesterase activity was .apprx. 35-50% low-salt-soluble and 45-65% detergent-soluble in various developmental stages and brain areas, with an increase during development of the detergent-soluble fraction of the light form. Pseudocholinesterase activity was mostly low-salt-soluble and sedimented as 1 component of 10-11S in all areas and developmental stages. Data suggest noncoordinate regulation of brain acetylcholinesterase and pseudocholinesterase. The expression of acetylcholinesterase forms within embryonic brain areas evidently depends on cell type composition and on development.