Stress accelerates neural degeneration and exaggerates motor symptoms in a rat model of Parkinson's disease

Eur J Neurosci. 2008 Apr;27(8):2133-46. doi: 10.1111/j.1460-9568.2008.06177.x.


The causes of most cases of Parkinson's disease (PD) are still poorly understood. Here we show that chronic stress and elevated corticosterone levels exaggerate motor deficits and neurodegenerative events in a Parkinson's disease rat model. Animals were tested in skilled and non-skilled movement while being exposed to daily restraint stress or oral corticosterone treatment. Stress and corticosterone compromised normal motor function and exaggerated motor deficits caused by unilateral 6-hydroxydopamine lesion of the nigrostriatal bundle. Moreover, stress and corticosterone treatments diminished the ability to acquire compensatory strategies in limb use during skilled reaching and skilled walking. In contrast, lesion control animals were able to significantly improve in the ability of skilled limb use during the repeated test sessions. The exaggerated motor impairments in stress-treated animals were related to accelerated loss of midbrain dopamine-producing neurons during the first week postlesion. Correlation analysis revealed a significant connection between loss of tyrosine hydroxylase-positive cells and increase in Fluoro-Jade-positive cells only in stress- and corticosterone-treated animals. Furthermore, stress and elevated corticosterone levels caused greater permanent loss of midbrain neurons than found in non-treated lesion animals. These findings demonstrate that stress and elevated corticosterone levels can exaggerate nigral neuronal loss and motor symptoms in a rat analogue of PD. It is therefore possible that stress represents a key factor in the pathogenesis of human PD by impeding functional and structural compensation and exaggerating neurodegenerative processes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain / physiopathology
  • Corticosterone / pharmacology*
  • Female
  • Motor Activity / drug effects
  • Movement Disorders / etiology*
  • Nerve Degeneration / etiology*
  • Nerve Degeneration / pathology
  • Parkinsonian Disorders / pathology*
  • Parkinsonian Disorders / physiopathology
  • Rats
  • Rats, Long-Evans
  • Stress, Psychological / complications*


  • Corticosterone