Expression of cell-cycle-related proteins and excitoxicity

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Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons
10:36

Modeling Neuronal Death and Degeneration in Mouse Primary Cerebellar Granule Neurons

Published on: November 6, 2017

D Uberti1, E Meli, M Memo

  • 1Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Brescia, Italy.

Amino Acids
|October 10, 2002
PubMed

Insights

N-methyl-D-aspartate (NMDA) exposure increases p53 protein levels in cortical neurons, triggering cell death pathways. This study extends previous findings, showing NMDA-induced neurodegeneration activates cellular proliferation events.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Previous research indicated p53's role in excitatory amino acid-induced neuronal cell death.
  • The functional contribution of p53 in primary neurons was previously suggested.

Purpose of the Study:

  • To investigate the role of p53 in N-methyl-D-aspartate (NMDA)-induced cell death in cortical neurons.
  • To determine if NMDA treatment affects p53 protein levels and downstream targets in cortical neurons.

Main Methods:

  • Primary cortical neurons were treated with varying concentrations of NMDA (300 microM and 2 mM).
  • p53 and gadd45 protein levels were assessed over time using immunofluorescence staining.
  • Time- and concentration-dependency of NMDA effects were analyzed.

Main Results:

  • NMDA exposure significantly enhanced p53 protein levels in cortical neurons, evident within 60 minutes.
  • Maximal p53 induction occurred at 3 hours post-treatment and was concentration-dependent.
  • NMDA treatment also increased gadd45 protein levels, correlating with peak p53 induction.

Conclusions:

  • The findings extend the paradigm of p53 involvement in excitotoxicity to cortical neurons.
  • NMDA-induced neurodegeneration activates cellular events typically associated with proliferation.
  • This suggests a complex cellular response in degenerating neurons involving p53 and gadd45.

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