Stimulation of the rat subthalamic nucleus is neuroprotective following significant nigral dopamine neuron loss

Neurobiol Dis. 2010 Jul;39(1):105-15. doi: 10.1016/j.nbd.2010.03.009. Epub 2010 Mar 20.

Abstract

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson's disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting neurotoxins. The present study examined whether STN-DBS can provide neuroprotection in the face of prior significant nigral DA neuron loss similar to PD patients at the time of diagnosis. STN-DBS between 2 and 4 weeks after intrastriatal 6-hydroxydopamine (6-OHDA) provided significant sparing of DA neurons in the SN of rats. This effect was not due to inadvertent lesioning of the STN and was dependent upon proper electrode placement. Since STN-DBS appears to have significant neuroprotective properties, initiation of STN-DBS earlier in the course of PD may provide added neuroprotective benefits in addition to its ability to provide symptomatic relief.

Publication types

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

MeSH terms

  • Animals
  • Cell Death / physiology
  • Cytoprotection / physiology*
  • Deep Brain Stimulation / methods*
  • Disease Models, Animal
  • Dopamine / biosynthesis*
  • Male
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Nerve Degeneration / prevention & control*
  • Neural Inhibition / physiology
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / metabolism
  • Substantia Nigra / pathology*
  • Subthalamic Nucleus / metabolism
  • Subthalamic Nucleus / pathology
  • Subthalamic Nucleus / physiology*
  • Treatment Outcome

Substances

  • Dopamine