Protein aggregation containing β-amyloid, α-synuclein and hyperphosphorylated τ in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure.
BACKGROUND
Protein aggregates containing alpha-synuclein, beta-amyloid and hyperphosphorylated tau are commonly found during neurodegenerative processes which is often accompanied by the impairment of mitochondrial complex I respiratory chain and dysfunction of cellular systems of protein degradation. In view of this, we aimed to develop an in vitro model to study protein aggregation associated to neurodegenerative diseases using cultured cells from hippocampus, locus coeruleus and substantia nigra of newborn Lewis rats exposed to 0.5, 1, 10 and 25 nM of rotenone, which is an agricultural pesticide, for 48 hours.


RESULTS
We demonstrated that the proportion of cells in culture is approximately the same as found in the brain nuclei they were extracted from. Rotenone at 0.5 nM was able to induce alpha-synuclein and beta amyloid aggregation, as well as increased hyperphosphorylation of tau, although high concentrations of this pesticide (over 1 nM) lead cells to death before protein aggregation. We also demonstrated that the 14 kDa isoform of alpha-synuclein is not present in newborn Lewis rats.


CONCLUSIONS
Rotenone exposure may lead to constitutive protein aggregation in vitro, which may be of relevance to study the mechanisms involved in idiopathic neurodegeneration.
Department of Neurology, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil.
Rodrigo S
RS
Chaves
Thaiany Q
TQ
Melo
Stephanie A
SA
Martins
Merari F R
MF
Ferrari
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007306:Insecticides / Q000633:toxicity; D008125:Locus Coeruleus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D046912:Multiprotein Complexes / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011917:Rats, Inbred Lew; D012402:Rotenone / Q000633:toxicity; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D007306:Insecticides; D046912:Multiprotein Complexes; D051844:alpha-Synuclein; D016875:tau Proteins; D012402:Rotenone