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1.
Acta Pharmacol Sin ; 40(4): 425-440, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30382185

RESUMO

Vascular dementia (VD) results from accumulated damage in the vascular system, which is characterized by progressive impairments in memory and cognition and is second only to Alzheimer's disease (AD) in prevalence among all types of dementia. In contrast to AD, there is no FDA-approved treatment for VD owing to its multiple etiologies. In this study, we investigated whether CZ-7, a new derivative of Claulansine F (Clau F) with verified neuroprotective activity in vitro, could ameliorate the cognitive impairment of rats with permanent occlusion of bilateral common carotid arteries (2VO) and its potential mechanisms of action. The 2VO rats were orally administered CZ-7 (10, 20, 40 mg/kg) from day 27 to day 53 post-surgery. Morris water maze tests conducted at day 48-51 revealed that CZ-7 administration significantly reduced the escape latency in 2VO rats. After the rats were sacrificed on day 53, morphological studies using Nissl and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining showed that administration of CZ-7 markedly attenuated the pathological changes in CA1-CA3 area of the hippocampus, including neuronal cell loss, nuclear shrinkage, and dark staining of neurons, and significantly decreased the chronic cerebral hypoperfusion-induced cell loss. Klüver-Barrera staining study revealed that CZ-7 administration significantly improved the white matter lesions. 8-OHdG and reactive oxygen species (ROS) immunofluorescent analyses showed that CZ-7 administration significantly decreased oxidative stress in CA1-CA3 area of the hippocampus. Finally, we found that the CZ-7-improved oxidative stress might be mediated via the Nrf2 pathway, evidenced by the double immunofluorescent staining of Nrf2 and the elevation of expression levels of oxidative stress proteins HO-1 and NQO1. In conclusion, CZ-7 has therapeutic potential for VD by alleviating oxidative stress injury through Nrf2-mediated antioxidant responses.


Assuntos
Antioxidantes/metabolismo , Artéria Carótida Primitiva/efeitos dos fármacos , Demência Vascular/tratamento farmacológico , Fator 2 Relacionado a NF-E2/metabolismo , Animais , Artéria Carótida Primitiva/metabolismo , Artéria Carótida Primitiva/patologia , Demência Vascular/metabolismo , Demência Vascular/patologia , Masculino , Estrutura Molecular , Ratos , Ratos Wistar
2.
Brain Res Bull ; 144: 68-74, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30472149

RESUMO

Since the metabolic disorder may be the high risk that contribute to the progress of Alzheimer's disease (AD). Overtaken of High-fat, high-glucose or high-cholesterol diet may hasten the incidence of AD in later life, due to the metabolic dysfunction. But the metabolism of lipid in brain and the exact effect of lipid to brain or to the AD's pathological remain controversial. Here we summarize correlates of lipid metabolism and AD to provide more foundation for the daily nursing of AD sensitive patients.


Assuntos
Doença de Alzheimer/metabolismo , Metabolismo dos Lipídeos/fisiologia , Adipocinas/metabolismo , Tecido Adiposo/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Dieta , Humanos , Células-Tronco Mesenquimais/fisiologia
3.
Brain Res Bull ; 140: 162-168, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29730417

RESUMO

Myelin is a membrane wrapped around the axon of the nerve cell, which is composed of the mature oligodendrocytes. The role of myelin is to insulate and prevent the nerve electrical impulses from the axon of the neurons to the axons of the other neurons, which is essential for the proper functioning of the nervous system. Minor changes in myelin thickness could lead to substantial changes in conduction speed and may thus alter neural circuit function. Demyelination is the myelin damage, which characterized by the loss of nerve sheath and the relative fatigue of the neuronal sheath and axon. Studies have shown that myelin injury may be closely related to neurodegenerative diseases and may be an early diagnostic criteria and therapeutic target. Thus this review summarizes the recent result of pathologic effect and signal pathways of myelin injury in neurodegenerative diseases, especially the Alzheimer's disease to provide new and effective therapeutic targets.


Assuntos
Doença de Alzheimer/patologia , Doença de Alzheimer/fisiopatologia , Sistema Nervoso Central/patologia , Sistema Nervoso Central/fisiopatologia , Bainha de Mielina/patologia , Bainha de Mielina/fisiologia , Animais , Humanos
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