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Related Experiment Videos

Cortical selective vulnerability in motor neuron disease: a morphometric study.

S Maekawa1, S Al-Sarraj, M Kibble

  • 1Department of Neurology, Institute of Psychiatry, De Crespigny Park, London SE5 8AF, UK. spgtpnl@iop.kcl.ac.uk

Brain : a Journal of Neurology
|May 8, 2004
PubMed
Summary

Motor neuron disease (MND), also known as amyotrophic lateral sclerosis, causes widespread loss of pyramidal neurons and interneurons in the brain. This neuronal loss occurs in areas beyond the motor cortex, indicating MND is a multisystem disorder.

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Area of Science:

  • Neuroscience
  • Neuropathology

Background:

  • Neuroimaging studies show functional abnormalities in motor and extramotor cortical areas in motor neuron disease (MND, amyotrophic lateral sclerosis).
  • The precise nature of cortical lesions and neuronal loss in MND remains poorly understood, particularly in extramotor regions.

Purpose of the Study:

  • To quantify neuronal loss in the primary motor cortex (PMC) and extramotor areas (DLPFC, ACC) in MND patients.
  • To investigate the density and size of pyramidal neurons and specific interneurons in affected cortical regions.

Main Methods:

  • Used SMI-32 antibody to analyze density and size of pyramidal neurons in cortical layer V of PMC, DLPFC, and ACC.
  • Examined interneurons (calbindin-D(28K), parvalbumin, calretinin) in the same cortical areas of 13 MND and 8 control subjects.

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Main Results:

  • Significant reduction in SMI-32-immunoreactive pyramidal neuron density in cortical layer V of PMC, DLPFC, and ACC in MND patients (approx. 25% reduction).
  • Significant differences in calbindin-D(28K)-immunoreactive interneuron densities observed in cortical layers V and VI in MND cases.
  • Trends towards reduced calretinin- and parvalbumin-immunoreactive interneuron densities were noted in specific layers.

Conclusions:

  • Neuronal loss, including pyramidal neurons and GABAergic interneurons, is more widespread in MND than previously recognized.
  • The findings support classifying MND as a multisystem disorder, affecting areas beyond primary motor control.
  • Cortical lesions contribute to neuroimaging and cognitive abnormalities observed in MND.