Studies of the potentially endogenous toxin TaClo (1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline) in neuronal and glial cell cultures.
1-Trichloromethyl-1,2,3,4-tetrahydro-beta-carboline (TaClo) is the first representative of a new class of highly halogenated heterocycles. The similarity of the beta-carboline framework to the chemical structure of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) prompted us to investigate the neurotoxic potential of this compound. For this purpose, primary cell cultures of C57/B16 mouse mesencephalon containing dopaminergic neurons were used. Cells were grown for 10 days and exposed to the toxin for 24 hours. The morphological changes observed in tyrosine hydroxylase immunoreactive (TH-IR) neurons and glial cells included swollen dendrites and soma, loss of axons and dendrites. At a TaClo concentration of 100 microM, the number of TH-IR neurons was decreased by 50%. In case of astrocyte cultures, changes became evident and at concentrations between 50-100 microM, a cell loss of 50% was observed. Furthermore, uptake of dopamine (DA) was reduced by 43% at 100 microM TaClo. Simultaneously, the DA content was significantly reduced by 66% at 100 microM.
Rausch
W D
WD
Institute of Medical Chemistry, University of Veterinary Medicine, Vienna, Austria.
Abdel-mohsen
M
M
Koutsilieri
E
E
Chan
W W
WW
Bringmann
G
G
D000818:Animals; D002243:Carbolines / Q000633:toxicity*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism; D005260:Female; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*
D002243:Carbolines; D009498:Neurotoxins; C067372:1-trichloromethyl-1,2,3,4-tetrahydro-beta-carboline; D004298:Dopamine