The cross-hemispheric nigrostriatal pathway prevents the expression of levodopa-induced dyskinesias.

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Parkinson's disease (PD) is a neurodegenerative movement disorder that is routinely treated with levodopa. Unfortunately, long-term dopamine replacement therapy using levodopa leads to levodopa-induced dyskinesias (LID), a significant and disabling side-effect. enter image description here

Clinical findings indicate that levodopa-induced dyskinesias typically only occurs following the progression of Parkinson's disease motor symptoms from the unilateral (Hoehn and Yahr (HY) Stage I) to the bilateral stage (HY Stage II).

This suggests the presence of some compensatory interhemispheric mechanisms that delay the occurrence of levodopa-induced dyskinesias.

The scientists investigated the role of interhemispheric connections of the nigrostriatal pathway on levodopa-induced dyskinesias expression in a rat model of Parkinson's disease.

The striatum of one hemisphere of rats was first injected with a retrograde tracer to label the ipsi- and cross-hemispheric nigrostriatal pathways.

Rats were then split into groups and unilaterally lesioned in the striatum or medial forebrain bundle of the tracer-injected hemisphere to induce varying levels of hemiparkinsonism.

Finally, rats were treated with levodopa and tested for the expression of levodopa-induced dyskinesias.

Distinct subsets emerged from rats that underwent the same lesioning paradigm based on levodopa-induced dyskinesias. Strikingly, non-dyskinetic rats had significant sparing of their cross-hemispheric nigrostriatal pathway projecting from the unlesioned hemisphere.

In contrast, dyskinetic rats only had a small proportion of this pathway survive lesioning. Crucially, both non-dyskinetic and dyskinetic rats had nearly identical levels of ipsi-hemispheric nigrostriatal pathway survival and parkinsonian motor deficits.

The data suggest that the survival of the cross-hemispheric nigrostriatal pathway plays a crucial role in preventing the expression of levodopa-induced dyskinesias and represents a potentially novel target to halt the progression of this devastating side-effect of a common anti-Parkinson's disease therapeutic.

Read the original article on Pubmed

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