Research reportTongue force and tongue motility are differently affected by unilateral vs bilateral nigrostriatal dopamine depletion in rats
Highlights
► Unilateral and bilateral nigrostriatal dopamine depletion affect orolingual motor function in rats. ► Both unilateral and bilateral nigrostriatal dopamine depletion decrease tongue force during licking. ► Tongue motility is decreased following unilateral but not bilateral nigrostriatal dopamine depletion. ► These results reveal a dissociation between these two movement modalities in the 6-hydroxydopamine rat model of Parkinson's disease.
Introduction
Parkinson's disease (PD) is an age-related neurodegenerative disease with characteristic symptoms that include bradykinesia, muscle rigidity, resting tremor and postural disturbances. These symptoms result primarily from degeneration of dopamine (DA) neurons in the substantia nigra, and depletion of DA in the nigrostriatal pathway [2], [11]. Preclinical studies have taken advantage of this well-characterized lesion by targeting the nigrostriatal pathway with neurotoxic agents such as 6-hydroxydopamine (6-OHDA) and MPTP (reviewed in [8]). These models, which typically involve unilateral DA depletion, generally recapitulate the cardinal symptoms of PD.
In addition to its cardinal symptoms, PD can also impair orolingual and pharyngeal motor function [1], [18], [27], [40]. These impairments can increase morbidity and mortality [25], primarily by disrupting the oral phase of swallowing [44]. In contrast to limb deficits (and with the exception of levodopa-induced oral dyskinesias [15]), preclinical attention to the primary effects of nigrostriatal DA depletion on orolingual motor function is a relatively recent development [13], [36], [41], [47]. These studies have reported that unilateral nigrostriatal DA depletion impairs tongue motility and protrusion force. The effects of bilateral nigrostriatal DA depletion on orolingual motor function have not been reported. This is an important consideration, not only because the tongue is a midline structure, but because onset in PD is typically unilateral, progressing bilaterally in later stages [23].
The purpose of this study was to compare the effects of bilateral and unilateral nigrostriatal DA depletion models on orolingual motor function in rats. Rats’ tongue force and tongue motility were measured as they licked water from an isometric disc as described previously by our lab [43], [51] and others [36], [41]. Orolingual motor function was measured prior to and for four weeks after treatment with 6-OHDA. We hypothesized that rats with bilateral striatal DA depletion would exhibit greater deficits in tongue force and tongue motility than rats with unilateral lesions.
Section snippets
Animals
Male Sprague–Dawley rats were obtained from Harlan. Rats were 3-months-old at the time of testing, were housed individually and were maintained on a 12 h light/dark cycle. After acclimation to the facility, access to water was gradually restricted with food made available ad libitum. The water restriction schedule allowed for slow weight gain and provided rats with necessary motivation to perform the water licking task. Procedures adhered to the Guide for the Care and Use of Laboratory Animals
Orolingual motor function
Pre-lesion values for body weight and the orolingual motor variables are provided in Table 1. None of the groups differed significantly with regard to body weight, tongue force, tongue motility or number of licks during these baseline measurements. Nigrostriatal DA depletion significantly attenuated tongue force in both lesion groups (Fig. 1). Although the effect for peak force did not differ significantly, maximum lick force was significantly decreased, F = 5.236, p = 0.01 (Fig. 2A and B). This
Discussion
In this study we found that nigrostriatal DA depletion impairs orolingual motor function in rats. While this finding is consistent with previous work, we extended these findings to report that bilateral DA depletion does not merely worsen the impairments observed in unilaterally lesioned rats, but rather affects orolingual motor function in qualitatively different ways. Specifically, although both lesion groups exhibited decreased tongue force, tongue motility deficits were limited to the
Acknowledgements
This work was supported by NIH grants AG023549, AG026491, the Kansas Training Program in Neurological and Rehabilitation Sciences (T32 HD57850), a Lied Endowed Basic Science Research grant, and by the Kansas Intellectual and Developmental Disabilities Research Center (HD02528).
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