Effect of manganese exposure on MPTP neurotoxicities.
We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. We randomly assigned adult male C57BL/6 mice (n=5-7 per group) the following treatments: SO, Mn(-) x MPTP(-); MO, Mn(+) x MPTP(-); SM, Mn(-) x MPTP(+); MM, Mn(+) x MPTP(+). Mn (MnCl(2).4H(2)O) was administered intraperitoneally at a dose of 2 mg/kg daily for 3 weeks. MPTP was then administered intraperitoneally at a dose of 30 mg/kg daily for 5 days in the SM and MM groups. Seven days after the last MPTP injection, the animals were sacrificed. Blood Mn levels were elevated in the Mn-exposed groups. Striatal Mn levels were not influenced by Mn treatment alone, however, they were decreased following MPTP. Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta (SNpc) were decreased significantly in the MPTP-exposed groups. Densities of TH- and dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU) were also decreased in the MPTP-treated groups. Furthermore, glial fibrillary acidic protein (GFAP)-ir astrocytes increased in the CPU with MPTP treatment. However, no effects were observed with Mn exposure. Concentrations of dopamine (DA), 3,4-dihydrophenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the corpus striatum were also decreased significantly with MPTP treatment alone, but Mn had no effect. Thus, decreased dopaminergic activities with MPTP led to decreased DA and its metabolites. Significant hypertrophies of GFAP-ir astrocytes in the globus pallidus (GP) were observed in Mn-exposed groups, especially in the MM group. MPTP targeted dopaminergic systems whereas Mn neurotoxicities occurred in the GP. In conclusion, our data suggest that Mn does not potentiate the neurotoxicity of MPTP.
Baek
Sun Yong
SY
Department of Anatomy, College of Medicine, Pusan University Hospital, Pusan, South Korea.
Lee
Myong-Jong
MJ
Jung
Hyun-Sil
HS
Kim
Hyun-Ju
HJ
Lee
Choong-Ryeol
CR
Yoo
Cheolin
C
Lee
Ji Ho
JH
Lee
Hun
H
Yoon
Chung Sik
CS
Kim
Young Hoon
YH
Park
Jungsun
J
Kim
Jae-Woo
JW
Jeon
Beom S
BS
Kim
Yangho
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D004357:Drug Synergism; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020267:MPTP Poisoning / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008345:Manganese / Q000097:blood / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D008345:Manganese; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine