Evaluation of neurobehavioral and neuroinflammatory end-points in the post-exposure period in rats sub-acutely exposed to manganese.
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.
Dinamene
D
Santos
I-Med.UL, Department of Toxicology and Food Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal.
Santos
S
Dinamene
M Camila
MC
Batoréu
Batoreu M
BM
Camila
I
I
Tavares de Almeida
L
L
Davis Randall
M Luísa
ML
Mateus
Mateus M
MM
Luisa
Vanda
V
Andrade
Andrade
A
Vanda
Ruben
R
Ramos
Ramos
R
Ruben
Edite
E
Torres
Torres
T
Edite
Michael
M
Aschner
Aschner
A
Michael
A P
AP
Marreilha dos Santos
A P
AP
Marreilha Dos Santos
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002540:Cerebral Cortex / Q000737:chemistry / Q000378:metabolism; D002712:Chlorides; D004305:Dose-Response Relationship, Drug; D023381:Endpoint Determination; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D008345:Manganese / Q000097:blood / Q000378:metabolism / Q000652:urine; D017895:Manganese Compounds; D020149:Manganese Poisoning / Q000473:pathology* / Q000523:psychology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013054:Spectrophotometry, Atomic
D002712:Chlorides; D005904:Glial Fibrillary Acidic Protein; D017895:Manganese Compounds; D008345:Manganese; C025340:manganese chloride
GFAP; Manganese neurotoxicity; Neurobehavioral assays; Neuroinflammation; TNF-α