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Primary Cultures of Rat Astrocytes and Microglia and Their Use in the Study of Amyotrophic Lateral Sclerosis
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Microglial activation correlates with disease progression and upper motor neuron clinical symptoms in amyotrophic

Johannes Brettschneider1, Jon B Toledo, Vivianna M Van Deerlin

  • 1Center for Neurodegenerative Disease Research, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, United States of America. Johannes.brettschneider@uni-ulm.de

Plos One
|June 22, 2012
PubMed
Abstract

Insights

Microglial pathology in the corticospinal tract (CST) of amyotrophic lateral sclerosis (ALS) patients correlates with disease progression and upper motor neuron (UMN) damage severity. The C9ORF72 repeat expansion was linked to increased microglial activity.

Area of Science:

  • Neuroscience
  • Neuropathology
  • Immunology

Background:

  • Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting motor neurons.
  • Upper motor neuron (UMN) damage is a key pathological feature in ALS.
  • The role of microglial inflammatory activity and the C9ORF72 repeat expansion in ALS pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the clinicopathological correlates of UMN damage in ALS.
  • To determine if the C9ORF72 repeat expansion is associated with altered microglial inflammatory activity.
  • To examine the relationship between microglial pathology, disease progression, and UMN deficits.

Main Methods:

  • Immunohistochemistry (IHC) using CD68 and Iba1 antibodies to assess microglial pathology.
  • Kluver-Barrera staining and myelin basic protein (MBP) IHC for myelin loss.
  • Neurofilament protein (TA51) IHC for axonal loss.
  • Analysis of 59 autopsy cases of ALS, including 9 with C9ORF72 repeat expansion.

Main Results:

  • Microglial pathology (CD68, Iba1) was more extensive in the corticospinal tract (CST) of rapidly progressing ALS cases.
  • ALS cases with C9ORF72 repeat expansion exhibited increased microglial pathology in the medulla and motor cortex, even after adjusting for disease duration.
  • Higher UMN scale scores correlated with increased microglial pathology in the cervical CST.
  • TDP-43 pathology was more pronounced in the motor cortex of rapidly progressing ALS cases.

Conclusions:

  • Microglial pathology in the CST of ALS is a significant correlate of disease progression.
  • The severity of UMN deficits in ALS is linked to the extent of microglial pathology.
  • The C9ORF72 repeat expansion is associated with heightened microglial inflammatory activity in specific brain regions in ALS.

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