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CC BY-NC-ND 4.0 · Arq Neuropsiquiatr 2016; 74(09): 737-744
DOI: 10.1590/0004-282X20160121
ARTICLES

Aged Lewis rats exposed to low and moderate doses of rotenone are a good model for studying the process of protein aggregation and its effects upon central nervous system cell physiology

Ratos Lewis idosos expostos a baixa e moderada doses de rotenona são um bom modelo para estudar o processo de agregação proteica e seus efeitos sobre a fisiologia celular do sistema nervoso central
Michael F. Almeida
1   Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, São Paulo SP, Brasil.
,
Carolliny M. Silva
1   Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, São Paulo SP, Brasil.
,
Aline M. D’Unhao
1   Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, São Paulo SP, Brasil.
,
Merari F. R. Ferrari
1   Universidade de São Paulo, Instituto de Biociências, Departamento de Genética e Biologia Evolutiva, São Paulo SP, Brasil.
› Author AffiliationsSupport: This study was supported by research grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (2013/08028-1; 2015/18961-2) and Conselho Nacional de desenvolvimento Cientifico e Tecnologico (CNPq) (471999/2013-0; 401670/2013-9). M.F.A and C.M.S. received fellowships from FAPESP; A.M.D. received fellowship from CNPq.
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ABSTRACT

Cell physiology is impaired before protein aggregation and this may be more relevant than inclusions themselves for neurodegeneration. The present study aimed to characterize an animal model to enable the analysis of the cell biology before and after protein aggregation. Ten-month-old Lewis rats were exposed either to 1 or 2 mg/kg/day of rotenone, delivered subcutaneously through mini-pumps, for one month. Hyperphosphorylated TAU, alpha-synuclein, amyloid-beta peptide and protein carbonylation (indicative of oxidative stress) were evaluated in the hippocampus, substantia nigra and locus coeruleus through immunohistochemistry or western blot. It was found that 2 mg/kg/day rotenone increased amyloid-beta peptide, hyperphosphorylation of TAU and alpha-synuclein. Rotenone at 1mg/kg/day did not alter protein levels. Protein carbonylation remained unchanged. This study demonstrated that aged Lewis rats exposed to a low dose of rotenone is a useful model to study cellular processes before protein aggregation, while the higher dose makes a good model to study the effects of protein inclusions.

RESUMO

A fisiologia celular está prejudicada antes da agregação proteica podendo ser mais importante para a neurodegeneração do que as próprias inclusões. Assim, o objetivo deste estudo é caracterizar um modelo animal para analisar os mecanismos e efeitos da agregação proteica. Ratos Lewis com 10 meses de idade foram expostos a rotenona (1 ou 2 mg/kg/dia), administrada subcutaneamente, utilizando minibombas osmóticas. Os níveis de peptídeo beta-amiloide, TAU hiperfosforilada, alfa-sinucleína e proteínas carboniladas (indicativo de estresse oxidativo) foram avaliados por imunohistoquímica e western blot no hipocampo, substância negra e locus coeruleus. Foi demonstrado que 2 mg/kg/dia de rotenona promoveu aumento do peptídeo beta-amiloide, hiperfosforilação da TAU e alfa-sinucleína. Já 1 mg/kg/dia de rotenona não alterou os níveis dessas proteína nessas regiões. As proteínas carboniladas não se alteraram. Foi demonstrado que ratos Lewis idosos expostos a baixas doses de rotenona são modelo de estudo dos processos celulares antes da agregação proteica, enquanto 2 mg/kg/dia de rotenona permite estudos sobre os efeitos da agregação proteica.

protein aggregates - rats - neurodegeneration
agregados proteicos - ratos - neurodegeneração

Support:

Support: This study was supported by research grants from Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) (2013/08028-1; 2015/18961-2) and Conselho Nacional de desenvolvimento Cientifico e Tecnologico (CNPq) (471999/2013-0; 401670/2013-9). M.F.A and C.M.S. received fellowships from FAPESP; A.M.D. received fellowship from CNPq.




Publication History

Received: 04 January 2016

Accepted: 08 June 2016

Article published online:
06 September 2023

© 2023. Academia Brasileira de Neurologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

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