Locomotor velocity and striatal adaptive gene expression changes of the direct and indirect pathways in Parkinsonian rats

Capper, C.; Kaelin-Lang, A. (2013). Locomotor velocity and striatal adaptive gene expression changes of the direct and indirect pathways in Parkinsonian rats. Journal of Parkinson's disease, 3(3), pp. 341-349. IOS Press 10.3233/JPD-130202

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology

UniBE Contributor:

Capper, Christine and Kaelin, Alain

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1877-718X

Publisher:

IOS Press

Language:

English

Submitter:

Ursula Aecherli Tobler

Date Deposited:

04 Jun 2014 14:27

Last Modified:

04 Jun 2014 14:27

Publisher DOI:

10.3233/JPD-130202

PubMed ID:

23948996

URI:

https://boris.unibe.ch/id/eprint/52110

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