Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons

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

Research output: Contribution to journalArticle

6 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)535-544
Number of pages10
JournalApoptosis
Volume11
Issue number4
DOIs
StatePublished - Mar 2006

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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Dopaminergic Neurons
Cell death
Neurons
Cell Death
Apoptosis
Cytoplasmic Structures
Neurologic Mutant Mice
Mitochondrial Swelling
Swelling
Nuclear Envelope
Glutamate Receptors
Golgi Apparatus
Membranes
Mesencephalon
Chromatin
Agglomeration
Chemical activation
Population

Keywords

  • Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropio nic acid
  • Glutamate receptors
  • Programmed cell death
  • Ultrastructure

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Cell Biology

Cite this

Dorsey, D. A., Mascó, D. H., Dikranian, K., Hyrc, K., Masciotra, L., Faddis, B., ... De Erausquin, G. A. (2006). Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons. Apoptosis, 11(4), 535-544. https://doi.org/10.1007/s10495-006-5268-y

Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons. / Dorsey, D. A.; Mascó, D. H.; Dikranian, K.; Hyrc, K.; Masciotra, L.; Faddis, B.; Soriano, M.; Gru, A. A.; Goldberg, M. P.; De Erausquin, G. A.

In: Apoptosis, Vol. 11, No. 4, 03.2006, p. 535-544.

Research output: Contribution to journalArticle

Dorsey, DA, Mascó, DH, Dikranian, K, Hyrc, K, Masciotra, L, Faddis, B, Soriano, M, Gru, AA, Goldberg, MP & De Erausquin, GA 2006, 'Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons', Apoptosis, vol. 11, no. 4, pp. 535-544. https://doi.org/10.1007/s10495-006-5268-y
Dorsey, D. A. ; Mascó, D. H. ; Dikranian, K. ; Hyrc, K. ; Masciotra, L. ; Faddis, B. ; Soriano, M. ; Gru, A. A. ; Goldberg, M. P. ; De Erausquin, G. A. / Ultrastructural characterization of alpha-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid-induced cell death in embryonic dopaminergic neurons. In: Apoptosis. 2006 ; Vol. 11, No. 4. pp. 535-544.
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