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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2018.tde-14032018-110624
Document
Author
Full name
Fernanda Crunfli
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2017
Supervisor
Committee
Torrão, Andréa da Silva (President)
Abdulkader, Fernando Rodrigues de Moraes
Dale, Camila Squarzoni
Sandoval, Maria Regina Lopes
Silva, Regina Helena da
Title in Portuguese
Efeito do agonista seletivo do receptor canabinoide 1 (CB1) em modelos de neurodegeneração induzida pela estreptozotocina.
Keywords in Portuguese
ACEA
Agonista CB1
Canabinoide
Estreptozotocina
Neurodegeneração
Neuroproteção
Abstract in Portuguese
A doença de Alzheimer (DA) é caracterizada por déficit cognitivo, associada com prejuízos no metabolismo energético e na via de sinalização da insulina encefálicos. A injeção intracerebroventricular de baixas doses de estreptozotocina (STZ) tem sido utilizada como um modelo experimental da DA em ratos. Nesse sentido, tem sido demonstrada a participação do sistema canabinoide em processos neurodegenerativos e seus efeitos neuroprotetores e anti-inflamatórios. O objetivo deste trabalho foi caracterizar as alterações comportamentais e moleculares em modelos experimentais (in vivo e in vitro) expostos à STZ e avaliar a participação do sistema canabinoide. A STZ produziu prejuízo cognitivo, morte celular por apoptose, deficiência na resposta à insulina e alterações na via IR/PI3K, semelhantes às encontradas na DA. O agonista canabinoide ACEA foi capaz de reverter o prejuízo cognitivo, modificar as alterações proteicas da via IR/PI3K, e regular positivamente a via anti-apoptótica, gerando uma neuroproteção.
Title in English
The effect of cannabinoid receptor 1 (CB1) selective agonist on models of streptozotocin-induced neurodegeneration.
Keywords in English
ACEA
Cannabinoid
CB1 agonist
Neurodegeneration
Neuroprotection
Streptozotocin
Abstract in English
Alzheimer's disease (AD) is characterized by cognitive deficit associated with energy metabolism impairment and changes in insulin signaling. In this context, low doses of intracerebroventricular streptozotocin (STZ) injection has been used as an experimental model of AD in rats. Several studies have demonstrated the participation of the cannabinoid system in neurodegenerative processes and its neuroprotective and anti-inflammatory properties. Thus, the aim of this work was to characterize the molecular and behavior alterations in experimental models (in vitro and in vivo) produced by STZ exposure and evaluate the cannabinoid system participation in these models. STZ was able to induce cognitive impairment, apoptosis cell death, impaired insulin response and alterations in the IR/PI3K signaling pathway, similar to those found in AD. CB1 agonist, ACEA reversed cognitive impairment and modified some protein changes in IR/PI3K pathway caused by STZ, and positively regulate the anti-apoptotic pathway, generating neuroprotection.
 
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Release Date
2020-03-13
Publishing Date
2018-03-14
 
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