Skip to main content

Table 2 Outcomes and risk of bias for pre-clinical studies on rodent models of Parkinson’s disease

From: The effects of exercise on cognition in Parkinson’s disease: a systematic review

Study Behavioral outcomes Neurobiological outcomes Major sources of risk of bias
Goes et al., 2013 [21] Forced exercise following onset of experimental PD: Changes in the striatum from forced exercise following onset of experimental PD: Performance bias: sedentary control animals were not exposed to the swimming training program, the warm water or handled to be dried off following each session.
  • Decreased marker of depression (tail suspension) • Decreased interleukin 1-beta levels (proinflammatory cytokines)
• Improved motor coordination (decreased falls on Rotarod test) • Attenuated inhibition of glutathione peroxidase activity, decreased glutathione reductase and glutathione S-transferase activity (all markers of oxidative stress)
• Improved long-term memory, but not short-term memory in object recognition test
• Increased dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels
Gorton et al., 2010 [17] Forced and voluntary exercise following onset of experimental PD: Forced and voluntary exercise following onset of experimental PD: Performance bias: each animal was only evaluated on one test.
• Improved motor learning (Rotarod) • Had no effect on levels of DA in the striatum and serotonin in the amygdala compared to saline controls
• Reduced anxiety in elevated plus maze (passive avoidance task, authors linked to cognition/memory)
• Forced and voluntary exercise increased DA in the striatum to similar levels following MPTP or saline administration
• Had no effect on markers of depression, sucrose preference and tail suspension (MPTP lesion also had no effect)
• Forced exercise increased 5HT in the nucleus accumbens in MPTP-treated mice compared to saline controls
Tajiri et al., 2010 [18] Exercise following onset of experimental PD: Exercise following onset of experimental PD: Information bias: exercise was started soon (24 hrs) after toxin administration, so the lesion may not represent a complete PD-like model.
• Improved cylinder test, amphetamine-induced rotational test (authors linked to cognitive-related behavior) • Preserved nigrostriatal dopamine neurons (increased tyrosine hydroxylase-positive fibers)
• Increased migration of new-born neural stem/progenitor cells toward striatum
• Up-regulated neurotrophic factors, BDNF and GDNF, in the striatum
Aguiar et al., 2009 [19] Forced and voluntary exercise before onset of experimental PD: Neurobiological outcomes not assessed Information bias: behavioral testing was soon (24 hrs) after the reserpine administration, so the lesion may not represent a complete PD-like model.
• Improved motor deficits following a high dose of reserpine
• Improved short-term social memory (tested through olfactory discrimination), with no deficit on motor or olfactory function from the low dose of reserpine
Pothakos et al., 2009 [20] Endurance exercise before and following onset of experimental chronic PD: Endurance exercise before and after onset of experimental chronic PD: Selection biases: there was not a group that received exercise and probenecid. There was also not a control group with only a saline injection. The effects of the control solution, probenecid, on cognition are not known.
• Reversed balance and gait performance, restored regular movement • Did not raise striatal DA (n = 6)
• Did not reverse loss of tyrosine-hydroxylase fibers in substantia nigra (pars compacta)
• Had no effect on learning (cued Morris water maze), amphetamine-stimulated locomotion or motor coordination
Fisher et al., 2004 [16] Exercise following onset of experimental PD: Exercise following onset of experimental PD: Information bias: the learning paradigm for behavioral results (learning to stay on the treadmill) relied substantially on motor capacity.
• Improved velocity and endurance on treadmill • Had no effect on tyrosine hydroxylase
• Sensory feedback not needed over time for behavioral response (i.e., maintaining a forward position on treadmill), authors suggested indicative of learning • Up-regulated dopamine D2 receptor mRNA expression
• Down-regulated striatal DAT
• Reversed increased nerve terminal glutamate in striatum (as a result of MPTP)