Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons |
| |
Authors: | D. A. Dorsey D. H. Mascó K. Dikranian K. Hyrc L. Masciotra B. Faddis M. Soriano A. A. Gru M. P. Goldberg G. A. de Erausquin MD PhD |
| |
Affiliation: | (1) Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri;(2) Department of Neurology, Washington University School of Medicine, St Louis, Missouri, USA;(3) Department of Otolaryngology, Washington University School of Medicine, St Louis, Missouri;(4) Departamento de Biología Celular, Universidad de Valencia, Valencia, Spain;(5) Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri, USA;(6) Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba;(7) Psychiatry and Neurology, Washington University School of Medicine, 660 S. Euclid Ave., Campus Box 8134, St Louis, MO, 63110 |
| |
Abstract: | Developing neuronal populations undergo significant attrition by natural cell death. Dopaminergic neurons in the substantia nigra pars compacta undergo apoptosis during synaptogenesis. Following this time window, destruction of the anatomic target of dopaminergic neurons results in dopaminergic cell death but the morphology is no longer apoptotic. We describe ultrastructural changes that appear unique to dying embryonic dopaminergic neurons. In primary cultures of mesencephalon, death of dopaminergic neurons is triggered by activation of glutamate receptors sensitive to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and differs ultrastructurally from both neuronal apoptosis or typical excitotoxicity. AMPA causes morphological changes selectively in dopaminergic neurons, without affecting other neurons in the same culture dishes. Two hours after the onset of treatment swelling of Golgi complexes is apparent. At 3 h, dopaminergic neurons display loss of membrane asymmetry (coinciding with commitment to die), as well as nuclear membrane invagination, irregular aggregation of chromatin, and mitochondrial swelling. Nuclear changes continue to worsen until loss of cytoplasmic structures and cell death begins to occur after 12 h. These changes are different from those described in neurons undergoing either apoptosis or excitotoxic death, but are similar to ultrastructural changes observed in spontaneous death of dopaminergic neurons in the natural mutant weaver mouse. |
| |
Keywords: | alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid programmed cell death glutamate receptors ultrastructure |
本文献已被 PubMed SpringerLink 等数据库收录! |
|