Fatigue reversibly reduced cortical and hippocampal dendritic spines concurrent with compromise of motor endurance and spatial memory

Neuroscience. 2009 Jul 21;161(4):1104-13. doi: 10.1016/j.neuroscience.2009.04.022. Epub 2009 Apr 17.


Fatigue could be induced following forced exercise, sickness, heat stroke or sleep disturbance and impaired brain-related functions such as concentration, attention and memory. Here we investigated whether fatigue altered the dendrites of central neurons. Central fatigue was induced by housing rats in cage with 1.5-cm deep water for 1-5 days. Three days of sleep deprivation seriously compromised rats' performance in weight-loaded forced swimming and spatial learning tests, and 5 days of treatment worsened it further. Combinations of intracellular dye injection and three-dimensional analysis revealed that dendritic spines on retrograde tracer-identified corticospinal neurons and Cornu Ammonis (CA)1 and CA3 pyramidal neurons were significantly reduced while the shape or length of the dendritic arbors was not altered. Three days of rest restored the spine loss and the degraded spatial learning and weight-loaded forced swimming performances to control levels. In conclusion, although we could not rule out additional non-hypothalamic-pituitary-adrenal stress, the apparent fatigue induced following a few days of sleep deprivation could change brain structurally and functionally and the effects were reversible with a few days of rest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Cortex / cytology
  • Cerebral Cortex / physiopathology*
  • Dendritic Spines / physiology*
  • Disks Large Homolog 4 Protein
  • Fatigue / complications*
  • Fatigue / physiopathology
  • Hippocampus / cytology
  • Hippocampus / physiopathology*
  • Imaging, Three-Dimensional
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Learning Disabilities / etiology
  • Learning Disabilities / physiopathology
  • Male
  • Maze Learning / physiology
  • Membrane Proteins / metabolism
  • Memory Disorders / etiology
  • Memory Disorders / physiopathology*
  • Neural Pathways / cytology
  • Neural Pathways / physiopathology
  • Neuronal Plasticity / physiology
  • Neurons / cytology
  • Neurons / physiology
  • Physical Endurance / physiology*
  • Pyramidal Cells / cytology
  • Pyramidal Cells / physiology
  • Rats
  • Sleep Deprivation / physiopathology
  • Spinal Cord / cytology
  • Spinal Cord / physiopathology
  • Swimming / physiology


  • Disks Large Homolog 4 Protein
  • Dlg4 protein, rat
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins