Exercise-induced rescue of tongue function without striatal dopamine sparing in a rat neurotoxin model of Parkinson disease

Abstract

Unilateral lesions to the medial forebrain bundle with 6-hydroxydopamine (6- OHDA) lead to force and timing deficits during a complex licking task. We hypothesized that training targeting tongue force generation during licking would improve timing and force measures and also lead to striatal dopamine sparing. Nine month-old male Fisher344/Brown Norway rats were used in this experiment. Sixteen rats were in the control condition and received tongue exercise (n=8) or no exercise (n=8). Fourteen rats were in the 6-OHDA lesion condition and underwent tongue exercise (n=7) and or no exercise (n=7). Following 4 weeks of training and post-training measures, all animals underwent bilateral stimulation of the hypoglossal nerves to measure muscle contractile properties and were then transcardially perfused and brain tissues collected for immunohistochemistry to examine striatal dopamine content. Results demonstrated that exercise animals performed better for maximal force, average force, and press rate than their no-exercise counterparts, and the 6-OHDA animals that underwent exercise performed as well as the control no exercise group. Interestingly, there were no group differences for tetanic muscle force, despite behavioral recovery of forces. Additionally, behavioral and neurochemical analyses indicate that there were no differences in striatal dopamine. Thus, targeted exercise can improve tongue force and timing deficits related to 6-OHDA lesions and this exercise likely has a central, versus peripheral (muscle strength) mechanism. However, this mechanism is not related to sparing of striatal dopamine content.

Vocal training, levodopa, and environment effects on ultrasonic vocalizations in a rat neurotoxin model of Parkinson disease

“…The net number of ipsiversive and contraversive quarter turns made during a 5 min period (20–25 min post-drug injection) was recorded to estimate the level of degeneration [24,26,60]. …”

“…Coronal, free-floating sections were stained for tyrosine hydroxylase (TH) immunoreactivity on every 5th section. Sections containing the basal ganglia (approximately Bregma 2.52 mm to −2.40 mm) were incubated in A) a primary antibody solution: rabbit anti-TH at 1:2000 (AB152, Millipore, Billerica, MA, USA), B) a biotinylated goat-anti rabbit secondary antibody solution (1:500 dilution, Millipore, Billerica, MA, USA), C) amplified using VECTASTAIN Elite ABC avidin-biotin system (Vector Laboratories, Burlingame, CA, USA), and D) visualized with a 3,3′-diaminobenzidine as described previously [26]. All sections were float mounted onto gelatin-coated slides, dehydrated in a series of alcohols and Histo-Clear™ (HS-200, National Diagnostics ® , Atlanta, Georgia, USA) and coverslipped.…”

“…[26,24] using ImageJ software (National Institutes of Health, Bethesda, MD). Briefly, a customized software program developed in Image J detected the optical density of threshold values for tissue positive for TH immunoreactivity.…”

“…The lesioned hemisphere is characterized as a percent loss of dopaminergic immunoreactivity. Moderate-to-severe 6-OHDA infusions were characterized by a percent loss greater than 70% [24,26]. …”

“…Chronic levodopa therapy improves some gross motor deficits such as rotational responses [36], but not skilled forelimb movements including reaching and grasping for food [37]. In rats, early exercise intervention (therapy) has been shown to protect viable dopamine neurons in the substantia nigra as well as improve behavioral sensorimotor outcomes [20,26,35,38,39]. However, exercise paradigms are typically carried-out in the drug-free state, and as with humans, and the potential interactions between levodopa and exercise are currently unknown.…”