Christine Capper-Loup1, Alain Kaelin-Lang. 1. Movement Disorders Center, Department of Neurology and Department of Clinical Research, Inselspital, Bern University Hospital and University of Bern, Switzerland.
Abstract
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.
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-OHDArats presented a tendency to an ipsilateral head turning and a low locomotor velocity. In 6-OHDArats 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 parkinsonianrat 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.
Authors: Megan E Fox; Maria A Mikhailova; Caroline E Bass; Pavel Takmakov; Raul R Gainetdinov; Evgeny A Budygin; R Mark Wightman Journal: Proc Natl Acad Sci U S A Date: 2016-06-13 Impact factor: 11.205
Authors: Robert Lindroos; Matthijs C Dorst; Kai Du; Marko Filipović; Daniel Keller; Maya Ketzef; Alexander K Kozlov; Arvind Kumar; Mikael Lindahl; Anu G Nair; Juan Pérez-Fernández; Sten Grillner; Gilad Silberberg; Jeanette Hellgren Kotaleski Journal: Front Neural Circuits Date: 2018-02-06 Impact factor: 3.492