TY - JOUR
T1 - Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese
AU - Dinamene, Santos
AU - Camila, Batoreu M.
AU - Tavares de Almeida, I.
AU - Davis Randall, L.
AU - Luisa, Mateus M.
AU - Vanda, Andrade
AU - Ruben, Ramos
AU - Edite, Torres
AU - Michael, Aschner
AU - Marreilha dos Santos, A. P.
N1 - Funding Information:
This study was funded by FCT (Foundation for Science and Technology of Portugal; SFRH/BD/64128/2009 ), by Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon , (i-Med.UL; strategic project, Pest- OE/SAU/UI4013/2011 ) and National Institute of Environmental Health Sciences ( ES R01 10563 and P30 000267 MA ). I would like to express my deep gratitude to Prof. Miguel Soares and Dr. Joana Rodrigues from the Histopathology Unit (HU) of Instituto Gulbenkian de Ciência (IGC) and Mrs. Yinchun Yu at Vanderbilt University.
PY - 2013/12/6
Y1 - 2013/12/6
N2 - 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.
AB - 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.
KW - GFAP
KW - Manganese neurotoxicity
KW - Neurobehavioral assays
KW - Neuroinflammation
KW - TNF-α
UR - http://www.scopus.com/inward/record.url?scp=84885808335&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84885808335&partnerID=8YFLogxK
U2 - 10.1016/j.tox.2013.09.008
DO - 10.1016/j.tox.2013.09.008
M3 - Article
C2 - 24060432
AN - SCOPUS:84885808335
SN - 0300-483X
VL - 314
SP - 95
EP - 99
JO - Toxicology
JF - Toxicology
IS - 1
ER -