Clearance of manganese from the rat substantia nigra following intra-nigral microinjections.
Chronic exposure to manganese (Mn) positively correlates with the occurrence of Parkinsonism but little is known about mechanisms of its neurotoxicity. In the present study, we determined the clearance of Mn from rat substantia nigra after its nigral injection and correlated it with the establishment of apomorphine-induced rotational behaviour and loss of striatal tyrosine hydroxylase (TH) immunoreactivity. Our results suggest that Mn is slowly cleared from the substantia nigra, following a first-order kinetics with a t(1/2) of 3 days. Appearance of apomorphine-induced rotational behaviour and loss of TH immunoreactivity within the striatum follows metal clearance were both detected 24 hours after intra-nigral Mn microinjection and maximal 72 hours after injection. The present data suggest that the cellular mechanisms induced by Mn and leading to dopaminergic cell death, occurred shortly after its injection and that the metal concentration needs to reach a threshold value to induce neurotoxic effects. This would indicate that nigral damages are a direct consequence of Mn accumulation.
Departatamento C. Fisiológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Caixa Postal 6001, CEP: 86051-970, Londrina, PR, Brazil.
Silvia
S
Ponzoni
Luis Carlos J
LC
Gaziri
Luiz R G
LR
Britto
Wagner J
WJ
Barreto
David
D
Blum
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000494:pharmacology; D005911:Gliosis / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics*; D017895:Manganese Compounds / Q000493:pharmacokinetics; D020149:Manganese Poisoning / Q000378:metabolism* / Q000503:physiopathology; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012399:Rotation; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D002712:Chlorides; D018491:Dopamine Agonists; D017895:Manganese Compounds; D008345:Manganese; D014446:Tyrosine 3-Monooxygenase; D001058:Apomorphine; C025340:manganese chloride; D004298:Dopamine