Protein aggregation containing beta-amyloid, alpha-synuclein and hyperphosphorylated tau in cultured cells of hippocampus, substantia nigra and locus coeruleus after rotenone exposure


Autoria(s): CHAVES, Rodrigo S; MELO, Thaiany Q; MARTINS, Stephanie A; FERRARI, Merari FR
Contribuinte(s)

UNIVERSIDADE DE SÃO PAULO

Data(s)

18/04/2012

18/04/2012

2010

Resumo

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 14kDa isoform of alpha-synuclein is not present in newborn Lewis rats. Conclusion: Rotenone exposure may lead to constitutive protein aggregation in vitro, which may be of relevance to study the mechanisms involved in idiopathic neurodegeneration.

We thank Edilaine Tampellini Santos and Livia Polichiso for their support during antibodies standardizing for immunohistochemistry and identification of aggregates in rat cells. This study was supported by research grants from FAPESP (2008/04480-9) and CNPq (472042/2008-4). R.S.C., T.Q.M. and S.A.M. received fellowships from FAPESP (2008/04655-3; 2009/02345-0 and 2009/00010-0, respectively).

Identificador

BMC NEUROSCIENCE, LONDON, v.11, NOV 10, 2010

1471-2202

http://producao.usp.br/handle/BDPI/15784

10.1186/1471-2202-11-144

http://dx.doi.org/10.1186/1471-2202-11-144

Idioma(s)

eng

Publicador

BIOMED CENTRAL LTD

Relação

BMC NEUROSCIENCE

Direitos

openAccess

Copyright BIOMED CENTRAL LTD

Palavras-Chave #PARKINSONS-DISEASE #LEWY BODIES #NERVOUS-SYSTEM #ANIMAL-MODELS #BRAIN #INHIBITION #PROTEASOME #NEURONS #NEURODEGENERATION #PHOSPHORYLATION #Neurosciences
Tipo

article

original article

publishedVersion