Activated microglia initiate motor neuron injury by a nitric oxide and glutamate-mediated mechanism

Weihua Zhao1, Wenjie Xie, Weidong Le

  • 1Department of Neurology, Baylor College of Medicine, One Baylor Plaza, NB 302, Houston, TX, 77030, USA.

Insights

Activated microglia release free radicals that injure motor neurons (MNs) by increasing glutamate receptor susceptibility. Astrocytes protect MNs by removing glutamate, but this is impaired by microglia.

Area of Science:

  • Neuroscience
  • Immunology
  • Cell Biology

Background:

  • Motor neuron (MN) death in neurodegenerative diseases may involve non-cell autonomous mechanisms.
  • Interactions between neurons and non-neuronal cells like microglia and astrocytes are critical.

Purpose of the Study:

  • To investigate how activated microglia and astrocytes influence motor neuron injury.
  • To define the molecular mechanisms underlying microglial-mediated motor neuron damage.

Main Methods:

  • Primary motor neuron cultures were used to study microglial activation effects.
  • Investigated the roles of reactive oxygen species, glutamate, and astrocytic glutamate transport.

Main Results:

  • Activated microglia induced motor neuron injury via peroxynitrite and glutamate.
  • Inhibition of microglial iNOS, catalase, or glutathione prevented injury.
  • Astrocytes protected motor neurons by glutamate uptake, which was impaired by activated microglia.

Conclusions:

  • Free radicals from activated microglia increase motor neuron AMPA/kainate receptor susceptibility to glutamate.
  • Astrocytic glutamate transport is crucial for motor neuron protection but is inhibited by activated microglia.

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