RESUMO
Alzheimer's disease (AD) is the most common cause of dementia and is characterized by the presence of ß-amyloid (Aß) plaques and defective autophagy in the brain, which is believed to cause neuronal dysfunction. By using APP/PS1 transgenic AD mice, we investigated the influence of orientin (Ori) on cognitive function and its underlying mechanisms in AD models. Our data indicated that Ori improved spatial learning and memory in APP/PS1 mice, possibly through decreasing brain Aß deposition and attenuating autophagy impairment. Ori decreased the LC3-II/I ratio, p62 and cathepsin D (Ctsd) protein levels and the number of autolysosomes, whereas the protein levels of Ulk1 and Beclin-1 were no different between the control and treatment groups, indicating increased autolysosome clearance and thus a decreased Aß burden in the brain. Our results showed that Ori could enhance autolysosome clearance, decrease brain Aß deposition and improve learning and memory in AD mice.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Autofagossomos/efeitos dos fármacos , Cognição , Flavonoides/uso terapêutico , Glucosídeos/uso terapêutico , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Autofagossomos/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteína Beclina-1/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Catepsina D/metabolismo , Feminino , Flavonoides/farmacologia , Glucosídeos/farmacologia , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Presenilina-1/genética , Proteína Sequestossoma-1/metabolismoRESUMO
Despite significant progress in the fabrication of prevascularized networks over the past decade, a number of challenges remain. One of the most relevant issues is the lack of three-dimensional (3D) structures, which limits the clinical applications of the engineered scaffolds. Another problem is the complexity of prevascularized networks in engineered scaffolds, which is still less than that of human tissues, especially in the case of mature and bulk tissues. Thus, there is still the need to develop more flexible methods to better simulate the structure of natural tissues. In this work, we used a versatile sacrificial template method to fabricate bulk scaffolds with spatial prevascularized networks. Soft poly(vinyl alcohol) (PVA) filaments were used to print the sacrificial template, and the receiving platform was a stepped shaft, allowing the sacrificial template to have a complex 3D structure. The obtained template was embedded into gelatin and microbial transglutaminase (mTG). The inner PVA template could be extracted from the enzymatic cross-linking system, and an engineered scaffold with spatial prevascularized networks was obtained. In vitro experiments demonstrated that the fabrication process is biocompatible with cells.
