Polychlorinated biphenyls alter expression of alpha-synuclein, synaptophysin and parkin in the rat brain.
Polychlorinated Biphenyls (PCBs)-induced changes in synaptic transmission are one of the effects of their neurotoxicity but the mechanism remains unknown. We assessed the in vivo effects of the PCBs mixture, Aroclor 1254 on the expression of neuronal proteins that are involved in the synaptic function and/or are associated with neurodegeneration. Wistar rats were treated orally with repeated doses of Aroclor 1254 and the levels of soluble alpha-synuclein, parkin, synaptophysin and amyloid precursor protein (APP) in the brain were determined by Western blotting. The results showed that Aroclor did not cause changes in the expression and processing of APP but at a dose 100 microg/g/day repeated for 6 days caused a decrease in the expression of alpha-synuclein in the cerebellum, cortex, hippocampus and hypothalamus of the animals sacrificed 2 days after treatment. The decrease in alpha-synuclein was accompanied by a transient increase in parkin and synaptophysin levels. Interestingly, in the hypothalamus the levels of alpha-synuclein remained decreased after 21 days post treatment perhaps due to regional differences in the PCBs elimination or perhaps a more specific interaction with the dopaminergic cells that are present in the hypothalamus that needs to be investigated further.
Malkiewicz
Katarzyna
K
Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, KFC, Novum, 141 86 Stockholm, Sweden. Katarzyna.Malkiewicz@ki.se
Mohammed
Roma
R
Folkesson
Ronnie
R
Winblad
Bengt
B
Szutowski
Miroslaw
M
Benedikz
Eirikur
E
D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D016708:Synaptophysin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051844:alpha-Synuclein / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D016708:Synaptophysin; D051844:alpha-Synuclein; D020111:Chlorodiphenyl (54% Chlorine); D044767:Ubiquitin-Protein Ligases; C111567:parkin protein