Evaluation of exercise-induced modulation of glial activation and dopaminergic damage in a rat model of Parkinson’s disease using [¹¹C]PBR28 and [¹⁸F]FDOPA PET

Abstract

Evidence suggests that exercise can modulate neuroinflammation and neuronal damage. We evaluated if such effects of exercise can be detected with positron emission tomography (PET) in a rat model of Parkinson's disease (PD). Rats were unilaterally injected in the striatum with 6-hydroxydopamine (PD rats) or saline (controls) and either remained sedentary (SED) or were forced to exercise three times per week for 40 min (EX). Motor and cognitive functions were evaluated by the open field, novel object recognition, and cylinder tests. At baseline, day 10 and 30, glial activation and dopamine synthesis were assessed by [11 C]PBR28 and [ 18 F]FDOPA PET, respectively. PET data were confirmed by immunohistochemical analysis of microglial (Iba-1) / astrocyte (GFAP) activation and tyrosine hydroxylase (TH). [11 C]PBR28 PET showed increased glial activation in striatum and hippocampus of PD rats at day 10, which had resolved at day 30. Exercise completely suppressed glial activation. Imaging results correlated well with post-mortem Iba-1 staining, but not with GFAP staining. [18 F]FDOPA PET, TH staining and behavioral tests indicate that 6-OHDA caused damage to dopaminergic neurons, which was partially prevented by exercise. These results show that exercise can modulate toxininduced glial activation and neuronal damage, which can be monitored noninvasively by PET.

Neuroinflammation and Cytokines in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): A Critical Review of Research Methods

“…This represents another reason to include non-healthy control groups in studies of putative ME/CFS biomarkers. Furthermore, there is some evidence from a rodent model that translocator protein radioligand uptake may be influenced by exercise (67), which is another argument for the importance of including sedentary controls in studies of ME/CFS. The use of sedentary-matched controls is an important consideration in all studies for which it is possible, not just PET scan studies.…”

Cardiovascular alterations in rats with Parkinsonism induced by 6-OHDA and treated with Domperidone

“…The Parkinson disease animal model used in the current study was Parkinsonism induced by 6-OHDA, as the toxicity of the Parkinson-like lesion inducing drug is relatively selective for dopaminergic neurons 2,25 . 6-OHDA was injected in the striatum, because according to previous studies 26,27 , Parkinsonism is characterized seven days after injections. In the present study, motor signs appeared, as shown in cylinder test, one week after drug injection.…”

“…Having installed the stereotaxic device (EFF 331- Insight™), incision, boring and injection of 0,5 µL of 6-OHDA cloridate (Sigma©) prepared in saline solution of ascorbic acid at 0,3% at concentration of 6 µg/µL were performed at coordinates AP: 0.0, LL:-2.7, DV:-4.5 and AP:0.5, LL:-3.2, DV-4 53,54 (right hemisphere) in 6-OHDA and 6-OHDA-D animals 26,27 . The same procedures were performed in Sham and Sham-D animals excepting that only saline solution of ascorbic acid at 0.3% was injected.…”

“…The animals were left into a transparent acrylic cylinder 20 cm in diameter and 30 cm in height and their exploratory behaviors was observed for 5 minutes in order to determine the number of touches on the cylinder wall with single right and left forepaw during their standing on rear limbs. Only animals with statistically significant preference for the right forepaw were counted among animals with Parkinsonism and included in group 6-OHDA 27 (Fig. 7B).…”

Physical Exercise Inhibits Inflammation and Microglial Activation

“…Exercise can inhibit microglial activation and alleviate pathogenesis of AD and PD in both patients and animal models by downregulating the expression of proinflammatory cytokines [123,124,125,126]. For example, in the APPswe/PS1De9 double-transgenic mouse model of AD, long-term treadmill exercise has been shown to suppress oxidative stress and microglia-induced neuroinflammation by decreasing the level of IL-1β and TNF-α [127].…”