RESUMEN
Alzheimer's disease (AD) is a progressive and degenerative disorder accompanied by emotional disturbance, especially anxiety and depression. More and more evidence shows that the imbalance of mitochondrial Ca2+ (mCa2+) homeostasis has a close connection with the pathogenesis of anxiety and depression. The Mitochondrial Calcium Uniporter (MCU), a key channel of mCa2+ uptake, induces the imbalance of mCa2+ homeostasis and may be a therapeutic target for anxiety and depression of AD. In the present study, we revealed for the first time that MCU knockdown in hippocampal neurons alleviated anxious and depressive behaviors of APP/PS1/tau mice through elevated plus-maze (EPM), elevated zero maze (EZM), sucrose preference test (SPT) and tail suspension test (TST). Western blot analysis results demonstrated that MCU knockdown in hippocampal neurons increased levels of glutamate decarboxylase 67 (GAD67), vesicular GABA transporter (vGAT) and GABAA receptor α1 (GABRA1) and activated the PKA-CREB-BDNF signaling pathway. This study indicates that MCU inhibition has the potential to be developed as a novel therapy for anxiety and depression in AD.
Asunto(s)
Enfermedad de Alzheimer , Ansiedad , Canales de Calcio , Depresión , Modelos Animales de Enfermedad , Hipocampo , Ratones Transgénicos , Neuronas , Animales , Enfermedad de Alzheimer/metabolismo , Hipocampo/metabolismo , Neuronas/metabolismo , Depresión/metabolismo , Canales de Calcio/metabolismo , Canales de Calcio/genética , Ansiedad/metabolismo , Ratones , Masculino , Mitocondrias/metabolismo , Glutamato Descarboxilasa/metabolismo , Técnicas de Silenciamiento del Gen/métodos , Conducta Animal/fisiologíaRESUMEN
A new fluorescent sensor for the determination of lemon yellow was developed based on nitrogen-doped carbon quantum dots (N-CQDs), which were prepared via a hydrothermal method with dried pomelo peel and L-tyrosine. The N-CQDs exhibited the blue fluorescence with a quantum yield of 28 %. The sensing principle of N-CQDs was quenched by lemon yellow via static quenching. The potential interfering substances showed no influence on the detection of lemon yellow. The limit of detection was 0.023 mg/L and lower than that of national standard. Furthermore, the synthesized N-CQDs have been successfully applied to the measurement of lemon yellow in real samples. Hence, the N-CQDs would be a promising sensor in food analysis.