, Volume 11, Issue 4, pp 535–544

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


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.


alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid programmed cell death glutamate receptors ultrastructure 


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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • D. A. Dorsey
    • 1
  • D. H. Mascó
    • 1
    • 6
  • K. Dikranian
    • 1
  • K. Hyrc
    • 2
  • L. Masciotra
    • 1
  • B. Faddis
    • 3
  • M. Soriano
    • 4
  • A. A. Gru
    • 1
  • M. P. Goldberg
    • 4
    • 5
  • G. A. de Erausquin
    • 1
    • 2
    • 5
    • 7
  1. 1.Department of PsychiatryWashington University School of MedicineSt Louis
  2. 2.Department of NeurologyWashington University School of MedicineSt LouisUSA
  3. 3.Department of OtolaryngologyWashington University School of MedicineSt Louis
  4. 4.Departamento de Biología CelularUniversidad de ValenciaValenciaSpain
  5. 5.Hope Center for Neurological DisordersWashington University School of MedicineSt LouisUSA
  6. 6.Facultad de Ciencias QuímicasUniversidad Nacional de CórdobaCórdoba
  7. 7.Psychiatry and NeurologyWashington University School of MedicineSt Louis

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