Andrew K.S. Ho1,2,*, Richard McLaughlin1, Albert
Chan1 and Rose Duffield1
1Department of Biomedical and Therapeutic Sciences, University
of Illinois College of Medicine at Peoria, PO Box 1649, Peoria, Illinois
61656, USA
2Department of Pharmacology, University of Illinois College of
Medicine at Urbana, Urbana, Illinois 61801, U.S.A.
* To whom correspondence should be addressed(1).
Abstract: 6-Hydroxydopamine (6-OHDA) was injected into the air sac
of developing chicken embryos on day E3 in order to study its effects on
cardiac development both morphologically and biochemically. A dose-dependent
teratogenic effect and fetotoxicity were observed in the 6-OHDA-treated
embryos. Cardiac malformations, including ventricular septal lesions, detachment
of the apical portions of the ventricles, cardiac hypertrophy, areas of
coagulative necrosis with pyknotic nuclei and broken nuclear membranes,
and swollen mitochondria were evident from gross histologic and ultrastructural
examinations. A LD50 of 0.3 mg/egg on day E11 was obtained. Biochemically,
6-OHDA induced a significant dose-dependent reduction in the total cardiac
choline acetyltransferase (ChAT) activities on days E8 and E11, followed
by a recovery on days E15 and E20. The effects on muscarinic acetylcholine
receptors (mAChRs) were less marked than on ChAT, indicating the effects
on the cholinergic nervous system development are primarily presynaptic.
There was a significant decrease in the level of norepinephrine (NE) and
a delay in the appearance of detectable cardiac NE. It is suggested that
6-OHDA-induced cardiac malformation can be a useful model to study the mechanisms
of cardiovascular development.
Keywords: 6-Hydroxydopamine, Cardiac, Adrenergic development