TY  - JOUR
A1  - Peres, Tanara V.
A1  - Eyng, Helena
A1  - Lopes, Samantha C.
A1  - Colle, Dirleise
A1  - Goncalves, Filipe M.
A1  - Venske, Debora K. R.
A1  - Lopes, Mark W.
A1  - Ben, Juliana
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael A.
A1  - Farina, Marcelo
A1  - Prediger, Rui D.
A1  - Leal, Rodrigo B.
T1  - Developmental exposure to manganese induces lasting motor and cognitive impairment in rats
JF  - Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system
N2  - Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum. (C) 2015 Elsevier Inc. All rights reserved.
KW  - Manganese
KW  - Neurotoxicity
KW  - Development
KW  - Motor coordination
KW  - Cognition
Y1  - 2015
U6  - https://doi.org/10.1016/j.neuro.2015.07.005
SN  - 0161-813X
SN  - 1872-9711
VL  - 50
SP  - 28
EP  - 37
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Peres, Tanara V.
A1  - Horning, Kyle J.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Bowman, Aaron B.
A1  - Aschner, Michael
T1  - Small Molecule Modifiers of In Vitro Manganese Transport Alter Toxicity In Vivo
JF  - Biological Trace Element Research
N2  - Manganese (Mn) is essential for several species and daily requirements are commonly met by an adequate diet. Mn overload may cause motor and psychiatric disturbances and may arise from an impaired or not fully developed excretion system, transporter malfunction and/or exposure to excessive levels of Mn. Therefore, deciphering processes regulating neuronal Mn homeostasis is essential to understand the mechanisms of Mn neurotoxicity. In the present study, we selected two small molecules (with opposing effects on Mn transport) from a previous high throughput screen of 40,167 to test their effects on Mn toxicity parameters in vivo using Caenorhabditis elegans. We pre-exposed worms to VU0063088 and VU0026921 for 30min followed by co-exposure for 1h with Mn and evaluated Mn accumulation, dopaminergic (DAergic) degeneration and worm survival. Control worms were exposed to vehicle (DMSO) and saline only. In pdat-1::GFP worms, with GFP labeled DAergic neurons, we observed a decrease of Mn-induced DAergic degeneration in the presence of both small molecules. This effect was also observed in an smf-2 knockout strain. SMF-2 is a regulator of Mn transport in the worms and this strain accumulates higher Mn levels. We did not observe improved survival in the presence of small molecules. Our results suggest that both VU0063088 and VU0026921 may modulate Mn levels in the worms through a mechanism that does not require SMF-2 and induce protection against Mn neurotoxicity.
KW  - Small molecules
KW  - Manganese
KW  - Neurotoxicity
KW  - C. elegans
KW  - Dopamine
Y1  - 2018
U6  - https://doi.org/10.1007/s12011-018-1531-7
SN  - 0163-4984
SN  - 1559-0720
VL  - 188
IS  - 1
SP  - 127
EP  - 134
PB  - Human press inc.
CY  - Totowa
ER  -