STUDIES OF THE POTENTIALLY ENDOGENOUS TOXIN TACLO TRICHLOROMETHYL-1,2,3,4-TETRAHYDRO-BETA-CARBOLINE) IN NEURONAL AND GLIAL-CELL CULTURES

-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is the firs t representative of a new class of highly halogenated heterocycles. Th e similarity of the beta-carboline framework to the chemical structure of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropy ridine (MPTP) prompted us to investigate the neurotoxic potential of t his compound. For this purpose, primary cell cultures of C57/B16 mouse mesencephalon containing dopaminergic neurons were used. Cells were g rown for 10 days and exposed to the toxin for 24 hours. The morphologi cal changes observed in tyrosine hydroxylase immunoreactive (TH-IR) ne urons and glial cells included swollen dendrites and soma, loss of axo ns and dendrites. At a TaClo concentration of 100 mu M, the number of TH-IR neurons was decreased by 50%. In case of astrocyte cultures, cha nges became evident and at concentrations between 50-100 mu M, a cell loss of 50% was observed. Furthermore, uptake of dopamine (DA) was red uced by 43% at 100 mu M TaClo. Simultaneously, the DA content was sign ificantly reduced by 66% at 100 mu M.