TY - JOUR
T1 - Involvement of striatal lipid peroxidation and inhibition of calcium influx into brain slices in neurobehavioral alterations in a rat model of short-term oral exposure to manganese
AU - Ávila, Daiana Silva
AU - Gubert, Priscila
AU - Fachinetto, Roselei
AU - Wagner, Caroline
AU - Aschner, Michael
AU - Rocha, João Batista Teixeira
AU - Soares, Félix Alexandre Antunes
N1 - Funding Information:
Work supported by the FINEP research “Rede Instituto Brasileiro de Neurosciência (IBN-Net)” # 01.06.0842-00. Additional supports were given by CNPq, FAPERGS and CAPES. P.G. is recipient of CNPq/PIBIC/UFSM fellowship. F.A.A.S. and J.B.T.R. are recipients of CNPq fellowships and D.S.A., R.F and C.W. are recipients of CAPES fellowships. This work was also supported by grants from NIEHS 10563 and DoD W81XWH-05-1-0239 (MA).
PY - 2008/11
Y1 - 2008/11
N2 - Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25 mg/mL of MnCl2 in their drinking water. MnCl2 intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, δ-aminolevulinate dehydratase (δ-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and 45Ca2+ influx into striatal slices was decreased in rats exposed to 25 mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased 45Ca2+ influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.
AB - Manganese is an essential element for biological systems, nevertheless occupational exposure to high levels of Mn can lead to neurodegenerative disorder, characterized by excessive Mn accumulation, especially in astrocytes of basal ganglia and symptoms closely resembling idiopathic Parkinson's disease (PD). The purpose of this study was to evaluate behavioral and biochemical alterations in adult rats exposed for 30 days to 10 and 25 mg/mL of MnCl2 in their drinking water. MnCl2 intoxicated rats showed impaired locomotor activity in comparison to control animals. Furthermore, lipid peroxidation were increased, δ-aminolevulinate dehydratase (δ-ALA-D, an enzyme sensitive to pro-oxidant situations) activity was inhibited and 45Ca2+ influx into striatal slices was decreased in rats exposed to 25 mg/mL of Mn, indicating that this brain region was markedly affected by short-term Mn exposure. In contrast, Mn exposure was not associated with characteristic extrapyramidal effects and did not modify protein oxidation, suggesting that the striatal damage represents early stages of Mn-induced damage. In addition, treatment with Mn was associated with reduced body weight gain, but there were no discernible alterations in liver and kidney function. In conclusion, Mn caused increased oxidative stress and decreased 45Ca2+ influx into the striatum, which are likely linked to impaired locomotor activity, but not with the occurrence of orofacial dyskinesia.
KW - Behavior alterations
KW - Calcium influx
KW - Manganese
KW - Oral short-term exposure
KW - Oxidative stress
KW - Striatum
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U2 - 10.1016/j.neuro.2008.08.004
DO - 10.1016/j.neuro.2008.08.004
M3 - Article
C2 - 18778733
AN - SCOPUS:84984550759
SN - 0161-813X
VL - 29
SP - 1062
EP - 1068
JO - Neurotoxicology
JF - Neurotoxicology
IS - 6
ER -