Marked changes in dendritic structure and spine density precede significant neuronal death in vulnerable cortical pyramidal neuron populations in the SOD1(G93A) mouse model of amyotrophic lateral sclerosis

Acta Neuropathol Commun. 2016 Aug 4;4(1):77. doi: 10.1186/s40478-016-0347-y.


Amyotrophic lateral sclerosis (ALS) is characterised by the death of upper (corticospinal) and lower motor neurons (MNs) with progressive muscle weakness. This incurable disease is clinically heterogeneous and its aetiology remains unknown. Increased excitability of corticospinal MNs has been observed prior to symptoms in human and rodent studies. Increased excitability has been correlated with structural changes in neuronal dendritic arbors and spines for decades. Here, using a modified Golgi-Cox staining method, we have made the first longitudinal study examining the dendrites of pyramidal neurons from the motor cortex, medial pre-frontal cortex, somatosensory cortex and entorhinal cortex of hSOD1(G93A) (SOD1) mice compared to wild-type (WT) littermate controls at postnatal (P) days 8-15, 28-35, 65-75 and 120. Progressive decreases in dendritic length and spine density commencing at pre-symptomatic ages (P8-15 or P28-35) were observed in layer V pyramidal neurons within the motor cortex and medial pre-frontal cortex of SOD1 mice compared to WT mice. Spine loss without concurrent dendritic pathology was present in the pyramidal neurons of the somatosensory cortex from disease-onset (P65-75). Our results from the SOD1 model suggest that dendritic and dendritic spine changes foreshadow and underpin the neuromotor phenotypes present in ALS and may contribute to the varied cognitive, executive function and extra-motor symptoms commonly seen in ALS patients. Determining if these phenomena are compensatory or maladaptive may help explain differential susceptibility of neurons to degeneration in ALS.

Keywords: Cortex; Dendrite; Spine density.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyotrophic Lateral Sclerosis / metabolism
  • Amyotrophic Lateral Sclerosis / pathology*
  • Animals
  • Cell Count
  • Cell Death* / physiology
  • Cell Size
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology*
  • Dendrites / metabolism
  • Dendrites / pathology*
  • Disease Models, Animal
  • Disease Progression
  • Humans
  • Longitudinal Studies
  • Mice, Transgenic
  • Organ Size
  • Pyramidal Cells / metabolism
  • Pyramidal Cells / pathology*
  • Superoxide Dismutase-1 / genetics
  • Superoxide Dismutase-1 / metabolism*
  • Time Factors


  • SOD1 protein, human
  • Superoxide Dismutase-1