Related Experiment Video
Updated: Aug 20, 2026

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
Published on: November 6, 2017
Transactivation of cell death signals by glutamate transmission in dopaminergic neurons
1Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA. erausquing@neuro.wustl.edu
Abstract:
The intrinsic susceptibility of dopaminergic neurons underlies the pathophysiology of Parkinson's disease and is possibly related to developmental injury in schizophrenia. However, the molecular substrates for this susceptibility are not well understood. We review the evidence of selective susceptibility of dopaminergic neurons to excessive glutamate receptor stimulation and discuss the molecular pathways that differentiate between physiological and pathological signaling leading to this particular form of neuronal death. In vitro as well as in vivo, activation of GluRAMPA causes concentration-dependent, severe pruning of neurites and selective death of dopaminergic neurons. In primary cultures of mesencephalon, this form of injury is mediated through release of calcium from intracellular stores (CICR), leading to loss of calcium homeostasis, oxidative stress, and activation of the transcription factor NFkappaB and the cell death protein p53. Post-translational modification of p53 may be an important target for neuroprotection in Parkinson's disease and perhaps in prevention of other neuropsychiatric disorders.
Related Concept Videos
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
Autophagic Cell Death
Autophagy and Apoptosis
Autophagy can activate apoptosis. In normal conditions, the autophagy activating protein Beclin-1 and pro-apoptotic...
The Extrinsic Apoptotic Pathway
Ligand-Gated Ion Channel Receptor: Gating Mechanism
Excitatory and Inhibitory Effects of Neurotransmitters
The Intrinsic Apoptotic Pathway
