Envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina em camundongos / Involvement of cellular signaling pathways in the antidepressant-like effect of quercetin in mice

Iandra Holzmann, Ana Paula Dalmagro, Camila André Cazarin, Priscila Laiz Zimath, Profa. Dra. Márcia Maria de Souza

Abstract


A elevada prevalência do Transtorno Depressivo Maior (TDM) tem recebido atenção da comunidade científica pois acarreta considerável sofrimento aos acometidos. As bases neurobiológicas do TDM são pouco conhecidas e as opções de tratamento farmacológico disponíveis são escassas. Nesse sentido, investigar potenciais moléculas com efeito antidepressivo é crucial. A pesquisa objetivou elucidar o envolvimento das vias de sinalização celular no efeito tipo-antidepressivo da quercetina. Para isso, vários grupos de camundongos Swiss fêmeas foram tratados com veículo (solução salina 0,9% estéril), quercetina 25 mg/Kg (v.o.), inibidor (i.c.v.) ou quercetina + inibidor. Foram utilizados os inibidores: H-89 (inibidor da proteína cinase A, 1 µg/sítio, i.c.v.); KN-62 (inibidor da proteína cinase dependente de Ca2+/calmodulina, 1 µg/sítio, i.c.v.); LY294002, um inibidor da fosfatidilinositol 3 cinase (PI3K, 10 nmol/sítio, i.c.v.); e um inibidor da proteína cinase regulada por sinal extracelular (ERK), o PD98059 (5 µg/sítio, i.c.v.). Os animais foram submetidos ao Teste de Suspensão pela Cauda (TSC) e Teste do Aberto (TCA) para avaliação do efeito tipo-antidepressivo e possíveis interferências dos tratamentos na capacidade locomotora. Todos os procedimentos foram aprovados pelo CEUA/UNIVALI 021/2013. Os resultados obtidos apontaram que a quercetina foi capaz de reduzir o tempo de imobilidade dos camundongos no TSC, entretanto, sem comprometer a capacidade locomotora dos animais (TCA). Além disso, foi constatado que os inibidores H-89, KN-62, LY294002 e PD98059 revereteram o efeito anti-imobilidade da quercetina. A administração dos inibidores isolados ou em associação com a quercetina, não comprometeram a locomoção dos camundongos. De forma geral, os dados apontam que a quercetina desencadeia efeito tipo-antidepressivo por intermédio da modulação da proteína cinase A (PKA), proteína cinase dependente de Ca2+/calmodulina (CaMKII), fosfatidilinositol 3 cinase (PI3K) e proteína cinase regulada por sinal extracelular (MAPKs/ERK).


Keywords


Sinalização celular; Quercetina; Flavonoide; Antidepressivo; Teste de Suspensão pela Cauda.

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DOI: https://doi.org/10.34119/bjhrv3n3-016

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