NONCHOLINERGIC, TROPHIC ACTION OF RECOMBINANT ACETYLCHOLINESTERASE ONMID-BRAIN DOPAMINERGIC-NEURONS

Acetylcholinesterase (AChE) is secreted from various brain regions suc h as the substantia nigra, where levels of this molecule are dispropor tionately higher than those of choline acetyltransferase. It is thus p ossible that AChE may have alternative, noncholinergic functions, one of which could be in development. Indeed, several recent studies have already demonstrated a neurotrophic action of AChE independent of hydr olysis of acetylcholine. In the developing nervous system the dominant forms of AChE differ from the tetramers (G(4)) that prevail in maturi ty, in that they are lower molecular weight monomers (G(1)) and dimers (G(2)) Therefore, the aims of this study were to explore the neurotro phic role of AChE by comparing the effects of mouse recombinant G(1) a nd G(4) AChE on the survival and development of midbrain tyrosine hydr oxylase immunoreactive neurons. Butyrylcholinesterase (BuChE), which a lso hydrolyses acetylcholine, and basic fibroblast growth factor (bFGF ), an established trophic factor for midbrain neurons, were also teste d. bFGF had no significant stimulatory effect: moreover, BuChE was als o inefficacious, suggesting that the action of AChE was independent of its catalytic site. In contrast, mouse recombinant G(1) and G(4) AChE both increased the survival as well as the outgrowth of the cultured neurons. However, G(1) AChE was more potent than G(4) AChE suggesting that developmental forms of AChE exist. The implications of this findi ng for physiological and pathological functioning of the nervous syste m are discussed. (C) 1997 Wiley-Liss, Inc.