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Dopamine Grafts in an Animal Model of Parkinson's Disease

Author Paul Kenyon

In humans, Parkinson's disease is associated with a profound loss of dopamine (DA) in the nigrostriatal system.

In rats, nigrostriatal lesions destroy a major DA pathway in the brain.

Therefore nigrostriatal lesions have been used as an animal model of Parkinson's disease. The following diagrams show a wire electrode being lowered into the brain. Then a small electrical current is passed down the wire to destroy the area around the tip of the electrode.

There are two nigrostriatal pathways - one on the left hand side and the other on the right hand side of the brain.Dunnett lesioned the nigrostriatal system on one side of brain.

When these rats are injected with amphetamine, DA is released from the intact nigrostriatal system on the non-lesioned side of the brain. This causes abnormal movement in the rat. The rat rotates towards it's lesioned side.

This is called ipsilateral rotational behavior, and can be measured in a special piece of apparatus :a rotometer .



It might be possible to treat Parkinson's disease by transplanting DA producing cells into the brain.

Dunnett tested this idea by implanting DA-producing cells into the caudate-putamen area of the brain. The picture shows the approximate location of this area in the brain. The cells were transplanted into the brain using a hollow tube called a 'cannula'.

Dunnett checked that DA was responsible for recovery of the animals' behavior by implanting serotonin-producing cells, or cells from the caudate-putamen into separate groups of rats with nigrostriatal lesions.


 

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These diagrams show the results of Dunnett's experiment :

  • note the high level of rotation in the Lesion group
  • contrast this with the low level of rotation in the Intact group
  • grafts of DA -producing cells overcome the effects of the lesion
  • grafts of serotonin ( 5-HT )-producing cells do not overcome the effects of the lesion
  • grafts of caudate-putamen cells ( CPu ) do not overcome the effects of the lesion

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