Locomotor velocity and striatal adaptive gene expression changes of the direct and indirect pathways in Parkinsonian rats.
BACKGROUND
In Parkinson's disease (PD), bradykinesia, or slowness of movement, only appears after a large striatal dopamine depletion. Compensatory mechanisms probably play a role in this delayed appearance of symptoms.


OBJECTIVE
Our hypothesis is that the striatal direct and indirect pathways participate in these compensatory mechanisms.


METHODS
We used the unilateral 6-hydroxydopamine (6-OHDA) rat model of PD and control animals. Four weeks after the lesion, the spontaneous locomotor activity of the rats was measured and then the animals were killed and their brain extracted. We quantified the mRNA expression of markers of the striatal direct and indirect pathways as well as the nigral expression of dopamine transporter (DAT) and tyrosine hydroxylase (TH) mRNA. We also carried out an immunohistochemistry for the striatal TH protein expression.


RESULTS
As expected, the unilateral 6-OHDA rats presented a tendency to an ipsilateral head turning and a low locomotor velocity. In 6-OHDA rats only, we observed a significant and positive correlation between locomotor velocity and both D1-class dopamine receptor (D1R) (direct pathway) and enkephalin (ENK) (indirect pathway) mRNA in the lesioned striatum, as well as between D1R and ENK mRNA.


CONCLUSIONS
Our results demonstrate a strong relationship between both direct and indirect pathways and spontaneous locomotor activity in the parkinsonian rat model. We suggest a synergy between both pathways which could play a role in compensatory mechanisms and may contribute to the delayed appearance of bradykinesia in PD.
Movement Disorders Center, Department of Neurology and Department of Clinical Research, Inselspital, Bern University Hospital and University of Bern, Switzerland.
Christine
C
Capper-Loup
Alain
A
Kaelin-Lang
D000818:Animals; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D004399:Dynorphins / Q000096:biosynthesis / Q000235:genetics; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000235:genetics* / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006892:Hydroxydopamines; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009043:Motor Activity / Q000502:physiology*; D017072:Neostriatum / Q000378:metabolism*; D009434:Neural Pathways; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000235:genetics* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics* / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D050483:Dopamine Plasma Membrane Transport Proteins; D004745:Enkephalins; D006892:Hydroxydopamines; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D004399:Dynorphins; D014446:Tyrosine 3-Monooxygenase; D005968:Glutamate Decarboxylase