Abstract
Forelimb stepping is a widely used test for the assessment of forelimb akinesia in hemiparkinsonian (hemi-PD) rats. The initiation time (IT) is considered the most sensitive parameter in the stepping test procedure. Here we propose a novel, reliable, and simple method for the measurement of IT of both forelimbs in both forehand and backhand directions in rats. Evaluating the same videos taken for quantifying adjusting steps, IT measurements were done without additional experiments. This is in contrast to the classical approach introduced by Olsson et al. (1995), in which separate experiments are necessary. We successfully applied our approach to hemi-PD rats intrastriatally treated with botulinum neurotoxin-A (BoNT-A). In naïve rats, an IT of about 0.62 s was found, and in right-sided hemi-PD rats the IT of the left forepaw increased to about 3.62 s. These hemi-PD rats showed, however, reduced ITs of the impaired left forepaws 1 month and the second time 7 months after induction of hemi-PD via the injection of 1 ng BoNT-A into the ipsilateral striatum, depending on post BoNT-A survival time. The method described offers the possibility of a precise and animal-friendly evaluation of IT in rats, including the beneficial effect of BoNT-A treatment in hemi-PD rats.
Highlights
In Parkinson’s disease (PD), bradykinesia and postural and gait impairments are leading symptoms [1,2] that are based on delayed movement initiation [3,4,5,6]
The catecholamine selective neurotoxin 6-OHDA has been widely used as a tool to produce dopamine (DA) axon terminal lesions in rats by injection into the medial forebrain bundle (MFB), the substantia nigra pars compacta (SNpc), or in various parts of the caudate-putamen (CPu = striatum) to induce a rat hemi-PD model [16,17,18,19]
As the initiation time (IT) seems to be an important and crucial parameter describing the degree of damage in hemi-PD, we focused on a refinement of its determination
Summary
In Parkinson’s disease (PD), bradykinesia and postural and gait impairments are leading symptoms [1,2] that are based on delayed movement initiation [3,4,5,6]. The 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian (hemi-PD) rat model is well characterized with respect to behavioral, biochemical, and morphological outcome [7,8,9,10,11,12,13,14,15]. The catecholamine selective neurotoxin 6-OHDA has been widely used as a tool to produce dopamine (DA) axon terminal lesions in rats by injection into the medial forebrain bundle (MFB), the substantia nigra pars compacta (SNpc), or in various parts of the caudate-putamen (CPu = striatum) to induce a rat hemi-PD model [16,17,18,19]. For behavioral characterization of hemi-PD or to measure the movement impairments of rats, drug-induced or spontaneous motor tests are used [5,23,24,25,26] An injection of 6-OHDA (10–24 μg) into the MFB produces profound neurodegeneration of the tyrosine hydroxylase-immunoreactive (TH-ir) neurons in the ipsilateral SNpc, followed by striatal DA depletion and significant motor deficits, mimicking a late stage of PD [20,21,22].
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