RESUMO
OBJECTIVE: Sesamin is known for its role in antioxidant, antiproliferative, antihypertensive, and neuroprotective activities. However, little is known about the role of sesamin in the development of emotional disorders. Here we investigated persistent inflammatory pain hypersensitivity and anxiety-like behaviors in the mouse suffering chronic pain. METHODS: Chronic inflammatory pain was induced by hind paw injection of complete Freund's adjuvant (CFA). Levels of protein were detected by Western blot. RESULTS: Administration of sesamin could induce anxiolytic activities but had no effect on analgesia. In the basolateral amygdala, a structure involving the anxiety development, sesamin attenuated the up-regulation of NR2B-containing N-methyl-d-aspartate receptors, GluR1 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor as well as phosphorylation of GluR1 at Ser831 (p-GluR1-Ser831), and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII-alpha) in the hind paw CFA-injected mice. In the same model, we found that the sesamin blocked the down-regulation of gamma-aminobutyric acid A (GABAA-alpha-2) receptors. CONCLUSION: Our findings show that sesamin reduces anxiety-like behaviors induced by chronic pain at least partially through regulating the GABAergic and glutamatergic transmission in the amygdala of mice.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/prevenção & controle , Complexo Nuclear Basolateral da Amígdala/metabolismo , Dor Crônica/fisiopatologia , Dioxóis/uso terapêutico , Modelos Animais de Doenças , Lignanas/uso terapêutico , Neurite (Inflamação)/fisiopatologia , Animais , Ansiedade/etiologia , Complexo Nuclear Basolateral da Amígdala/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Dor Crônica/etiologia , Dor Crônica/psicologia , Suplementos Nutricionais , Adjuvante de Freund/toxicidade , Temperatura Alta/efeitos adversos , Hiperalgesia/induzido quimicamente , Hiperalgesia/etiologia , Hiperalgesia/imunologia , Hiperalgesia/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Neuralgia/etiologia , Neuralgia/fisiopatologia , Neuralgia/psicologia , Neurite (Inflamação)/induzido quimicamente , Neurite (Inflamação)/etiologia , Neurite (Inflamação)/imunologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Fosforilação/efeitos dos fármacos , Pressão/efeitos adversos , Processamento de Proteína Pós-Traducional/efeitos dos fármacosRESUMO
Gastrodin is an active ingredient derived from the rhizome of Gastrodia elata. This compound is usually used to treat convulsive illness, dizziness, vertigo, and headache. This study aimed to investigate the effect of gastrodin on the autophagy of glial cells exposed to lipopolysaccharides (LPS, 1 µg/mL). Autophagy is a form of programmed cell death, although it also promotes cell survival. In cultured astrocytes, LPS exposure induced excessive autophagy and apoptosis, which were significantly prevented by the pretreatment cells with gastrodin (10 µM). The protective effects of gastrodin via autophagy inhibition were verified by the decreased levels of LC3-II, P62, and Beclin-1, which are classical markers for autophagy. Furthermore, gastrodin protected astrocytes from apoptosis through Bcl-2 and Bax signaling pathway. The treatment of astrocytes with rapamycin (500 nM), wortmannin (100 nM), and LY294002 (10 µM), which are inhibitors of mTOR and PI3K, respectively, eliminated the known effects of gastrodin on the inhibited Beclin-1 expression. Furthermore, gastrodin blocked the down-regulation of glutamine synthetase induced by LPS exposure in astrocytes. Our results suggest that gastrodin can be used as a preventive agent for the excessive autophagy induced by LPS.