Axonal transport of manganese and its relevance to selective neurotoxicity in the rat basal ganglia.
The present study provides evidence for anterograde axonal transport of manganese (Mn) in the basal ganglia. Microinjections of 54Mn into rat substantia nigra or striatum revealed region-specific accumulation and retention of the isotope in globus pallidus, striatum, thalamus and substantia nigra for up to at least 48 or 72 h respectively. Within 4 h after intrastriatal injection of 54Mn, radioactivity accumulated in the substantia nigra, suggesting axonal transport of the metal. Subsequent studies using bilateral 54Mn injections into striatum or substantia nigra and unilateral colchicine injections into or transection of the medial forebrain bundle confirmed axonal transport of Mn through these fibres. Selective destruction of the striatonigral or nigrostriatal pathways using quinolinic acid or 6-hydroxydopamine 2 weeks before injection of the isotope, revealed uptake of 54Mn by cell bodies of both gamma-aminobutyric acidergic striatal and dopaminergic nigral neurons and subsequent anterograde transport through striatonigral or nigrostriatal fibres. In addition, the quinolinic acid-lesioned striatum retained three times more radioactivity than the intact striatum. In conclusion, the present data suggest that both glial cells and striatonigral and nigrostriatal neurons are potential targets for Mn toxicity. These results and the selective neurotoxicity of Mn are discussed with respect to the iron transport protein transferrin, transferrin receptors, the iron storage protein ferritin, and mitochondrial dysfunction.
Sloot
W N
WN
TNO Nutrition and Food Research, Department of Neurotoxicology, Rijswijk, The Netherlands.
Gramsbergen
J B
JB
D000818:Animals; D001369:Axons / Q000187:drug effects*; D001479:Basal Ganglia / Q000187:drug effects*; D001692:Biological Transport / Q000187:drug effects; D003078:Colchicine; D003342:Corpus Striatum; D008297:Male; D008345:Manganese / Q000378:metabolism*; D008845:Microinjections; D016627:Oxidopamine; D017378:Quinolinic Acid; D011868:Radioisotopes; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra
D011868:Radioisotopes; D008345:Manganese; D016627:Oxidopamine; D017378:Quinolinic Acid; D003078:Colchicine