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1.
FASEB J ; 33(3): 4404-4417, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30576233

RESUMO

Alzheimer's disease (AD) is a leading cause of dementia. However, the mechanisms responsible for development of AD, especially for the sporadic variant, are still not clear. In our previous study, we discovered that a small noncoding RNA (miR-188-3p) targeting ß-site amyloid precursor protein cleaving enzyme (BACE)-1, a key enzyme responsible for Aß formation, plays an important role in the development of neuropathology in AD. In the present study, we identified that miR-338-5p, a new miRNA that also targets BACE1, contributes to AD neuropathology. We observed that expression of miR-338-5p was significantly down-regulated in the hippocampus of patients with AD and 5XFAD transgenic (TG) mice, an animal model of AD. Overexpression of miR-338-5p in the hippocampus of TG mice reduced BACE1 expression, Aß formation, and neuroinflammation. Overexpression of miR-338-5p functionally prevented impairments in long-term synaptic plasticity, learning ability, and memory retention in TG mice. In addition, we provide evidence that down-regulated expression of miR-338-5p in AD is regulated through the NF-κB signaling pathway. Our results suggest that down-regulated expression of miR-338-5p plays an important role in the development of AD.-Qian, Q., Zhang, J., He, F.-P., Bao, W.-X., Zheng, T.-T., Zhou, D.-M., Pan, H.-Y., Zhang, H., Zhang, X.-Q., He, X., Sun, B.-G., Luo, B.-Y., Chen, C., Peng, G.-P. Down-regulated expression of microRNA-338-5p contributes to neuropathology in Alzheimer's disease.


Assuntos
Doença de Alzheimer/genética , Hipocampo/metabolismo , MicroRNAs/fisiologia , Regiões 3' não Traduzidas , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/biossíntese , Secretases da Proteína Precursora do Amiloide/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Ácido Aspártico Endopeptidases/biossíntese , Ácido Aspártico Endopeptidases/genética , Células Cultivadas , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Inflamação , Masculino , Aprendizagem em Labirinto , Transtornos da Memória/genética , Transtornos da Memória/prevenção & controle , Camundongos , Camundongos Transgênicos , MicroRNAs/biossíntese , MicroRNAs/genética , NF-kappa B/fisiologia , Plasticidade Neuronal , Neurônios/metabolismo , Fragmentos de Peptídeos/metabolismo , Cultura Primária de Células , Proteínas Recombinantes/metabolismo
2.
Neural Regen Res ; 13(11): 1900-1906, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30233062

RESUMO

Auditory stimuli are proposed as beneficial neurorehabilitation methods in patients with disorders of consciousness. However, precise and accurate quantitative indices to estimate their potential effect remain scarce. Fourteen patients were recruited from the Neuro-Rehabilitation Unit of Hangzhou Hospital of Zhejiang Armed Police Corps of China. Altogether, there were seven cases of unresponsive wakefulness syndrome (five males and two females, aged 45.7 ± 16.8 years) and seven cases of minimally conscious state (six males and one female, aged 42.3 ± 20.8 years). Simultaneously, fourteen healthy controls (10 males and 4 females, aged 51.7 ± 9.7 years) also participated in this case-control experiment. Brain response to music, subjects' own name, and noise was monitored by quantitative electroencephalography (QEEG) in the resting state and with acoustic stimulation. Predictive QEEG values in various brain regions were investigated. Our results show that cerebral activation was high in subjects stimulated by their own name, especially in the temporal lobe in patients with disorders of consciousness, and the frontal lobe in the control group. Further, during resting and stimulation, QEEG index (δ + θ/α + ß ratio) negatively correlated with the Coma Recovery Scale-Revised score in traumatic disorders of consciousness patients. Hence, we speculate that a subject's own name might be an effective awakening therapy for patients with disorders of consciousness. Moreover, QEEG index in specific stimulation states may be used as a prognostic indicator for disorders of consciousness patients (sensitivity, 75%; specificity, 50%). This clinical study has been registered at ClinicalTrials.gov (identifier: NCT03385291).

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