Quantitative Analysis of Catecholamines in the Pink1 -/- Rat Model of Early-onset Parkinson's Disease.

Parkinson's disease (PD) related to homozygous mutations in the Pink1 gene is associated with nigrostriatal dopamine depletion and a wide range of sensorimotor deficits. In humans and animal models of PD, not all sensorimotor deficits are levodopa-responsive. We hypothesized that the underlying mechanisms of locomotion, limb control, and vocal communication behavior include other pathologies. Here, Pink1 -/- rats were treated with an oral dose of levodopa and limb motor and vocal communication behaviors were measured. Levodopa significantly improved some aspects of locomotion but did not improve ultrasonic vocalization intensity or frequency. Catecholamine concentrations in the striatum (SR), substantia nigra (SN), and locus coeruleus (LC) were analyzed to test the hypothesis that behavioral deficits would correlate to altered protein levels. There were no differences in dopamine concentrations in the SR and SN of Pink1 -/- animals compared to wild-type controls. There was a significant increase in norepinephrine concentration in the SN of Pink1 -/- animals. Moreover, an observed decrease in norepinephrine concentrations in the LC is consistent with the hypothesis that early-stage PD includes noradrenergic loss in the brainstem, and is congruent with a significant increase in catechol-O-methyltransferase expression in the LC of Pink1 -/- animals. Pearson's correlations showed that increases in time to traverse a tapered balance beam are significantly associated with reductions in striatal dopamine. Ultrasonic vocalization complexity was positively correlated with LC norepinephrine concentrations. These data support the evolving hypothesis that differences in neural substrates and early-onset noradrenergic mechanisms in the brainstem may contribute to pathogenesis in the Pink1 -/- rat. Published by Elsevier Ltd.