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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)