Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese - PubMed (original) (raw)

Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese

Dinamene Santos et al. Toxicology. 2013.

Erratum in

Abstract

Manganese (Mn) can cause manganism, a neurological disorder similar to Parkinson' Disease (PD). The neurobehavioral and neuroinflammatory end-points in the Mn post exposure period have not been studied yet. Rats were injected on alternate days with 8 doses of MnCl2 (25mg/kg) or saline, then euthanized 1, 10, 30 or 70 days following the last dose. Whole-blood (WB) (p<0.05), urine (p<0.05) and brain cortical (p<0.0001) Mn levels were significantly increased 24h after the last dose. Decreases in the rats' ambulation were noted 1, 10 and 30 days after the last Mn dose (p<0.001; p<0.05; p<0.001, respectively) and also in the rearing activity at the four time-points (p<0.05). Cortical glial fibrillary acid protein immunoreactivity (GFAP-ir) was significantly increased at 1, 10, 30 (p<0.0001) and 70 (p<0.001) days after the last Mn dose, as well as tumor necrosis α (TNF-α) levels (p<0.05) but just on day 1. Taken together, the results show that, during the 70-day clearance phase of Mn, the recovery is not immediate as behavioral alterations and neuroinflammation persist long after Mn is cleared from the cortical brain compartment.

Keywords: GFAP; Manganese neurotoxicity; Neurobehavioral assays; Neuroinflammation; TNF-α.

Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

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Figures

Figure 1

Figure 1

Mn concentrations in rats exposed to 8 doses of MnCl2 (25 mg/Kg, on alternate days) or saline (controls) sacrificed 1, 10, 30 or 70 days after the last dose; Data for each control group were compiled into a single control. (A) brain Mn concentration (n=5); (B) WB-Mn concentrations (n=5); (C) urine Mn concentrations (n=4). Bars represent mean ± SEM (n=5). * p<0.05, *** p<0.0001 indicate statistical difference from control group by one-way ANOVA followed by Bonferroni's multiple comparison tests.

Figure 1

Figure 1

Mn concentrations in rats exposed to 8 doses of MnCl2 (25 mg/Kg, on alternate days) or saline (controls) sacrificed 1, 10, 30 or 70 days after the last dose; Data for each control group were compiled into a single control. (A) brain Mn concentration (n=5); (B) WB-Mn concentrations (n=5); (C) urine Mn concentrations (n=4). Bars represent mean ± SEM (n=5). * p<0.05, *** p<0.0001 indicate statistical difference from control group by one-way ANOVA followed by Bonferroni's multiple comparison tests.

Figure 2

Figure 2

Neurobehavioral evaluation in rats exposed to 8 doses of MnCl2 (25 mg/Kg, on alternate days) or saline (controls) sacrificed 1, 10, 30 or 70 days after the last dose; (A) ambulation, number of crossings in the open field; (B) number of rearings in the open field. Bars represent mean ± SEM (n=5). * p<0.05** p<0.001*** p<0.0001 indicate statistical difference from the control group by one-way ANOVA followed by Bonferroni's multiple comparison tests.

Figure 3

Figure 3

Cortical astrocytic GFAP levels [expressed as relative fluorescence units (RFU)] in rats exposed to 8 doses of MnCl2 (25 mg/Kg, on alternate days) or saline (controls) sacrificed 1, 10, 30 or 70 days after the last dose; Data for each control group were compiled into a single control. Bars represent mean ± SEM (n=3). *** p<0.0001, ** p<0.001 indicate statistical difference from the control by one-way ANOVA followed by Bonferroni's multiple comparison tests.

Figure 4

Figure 4

TNF-α concentrations in rats exposed to 8 doses of MnCl2 (25 mg/Kg, on alternate days) or saline (controls) sacrificed 1, 10, 30 or 70 days after the last dose; Data for each control group were compiled into a single control. Bars represent mean ± SEM (n=5). * p<0.05 indicates statistical difference from control by one-way ANOVA followed by Bonferroni's multiple comparison tests.

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