High-Fat Diet Induces Neuroinflammation and Mitochondrial Impairment in Mice Cerebral Cortex and Synaptic Fraction
High-Fat Diet Induces Neuroinflammation and Mitochondrial Impairment in Mice Cerebral Cortex and Synaptic Fraction
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DOI：
10.3389/fncel.2019.00509
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发表时间：
2019-11-12
影响因子：
5.3
通讯作者：
Mollica, Maria Pina
中科院分区：
文献类型：
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作者：
Cavaliere, Gina;Trinchese, Giovanna;Mollica, Maria Pina
脑线粒体功能障碍与神经和神经退行性疾病的发展有关。位于突触的线粒体在提供能量支持突触功能和可塑性方面发挥着关键作用，因此它们的缺陷可能导致突触衰竭，这是神经退行性疾病的常见标志。高脂肪饮食（HFD）的消耗会增加大脑氧化应激并损害大脑线粒体功能，尽管其潜在机制尚不完全清楚。我们的研究目的是分析从饮食性肥胖小鼠模型中分离的脑皮层和突触体部分的神经炎症和线粒体功能障碍。雄性C57Bl/6小鼠分为两组，分别饲喂标准日粮和HFD，持续18周。治疗结束时，测定大鼠脑皮质和突触体部分的炎症（ELISA检测）、抗氧化状态（酶活性检测）、线粒体功能和效率（氧化能力和海马分析）、脑源性神经营养因子（BDNF）通路（western blot分析）。在HFD动物中，我们观察到大脑皮层和突触体部分的炎症参数和氧化应激增加，线粒体氧化能力下降。这些变化与BDNF的调节平行，BDNF是一种连接突触可塑性和能量代谢的大脑关键信号分子。hfd依赖性神经炎症对脑皮层BDNF通路和线粒体活性有负面影响。这种影响在突触区更为明显，在那里受损的能量供应可能对神经元的可塑性产生负面影响。
Brain mitochondrial dysfunction is involved in the development of neurological and neurodegenerative diseases. Mitochondria specifically located at synapses play a key role in providing energy to support synaptic functions and plasticity, thus their defects may lead to synaptic failure, which is a common hallmark of neurodegenerative diseases. High-Fat Diet (HFD) consumption increases brain oxidative stress and impairs brain mitochondrial functions, although the underlying mechanisms are not completely understood. The aim of our study is to analyze neuroinflammation and mitochondrial dysfunctions in brain cortex and synaptosomal fraction isolated from a mouse model of diet-induced obesity. Male C57Bl/6 mice were divided into two groups fed a standard diet or HFD for 18 weeks. At the end of the treatment, inflammation (detected by ELISA), antioxidant state (measured by enzymatic activity), mitochondrial functions and efficiency (detected by oxidative capacity and Seahorse analysis), and brain-derived neurotrophic factor (BDNF) pathway (analyzed by western blot) were determined in brain cortex and synaptosomal fraction. In HFD animals, we observed an increase in inflammatory parameters and oxidative stress and a decrease in mitochondrial oxidative capacity both in the brain cortex and synaptosomal fraction. These alterations parallel with modulation of BDNF, a brain key signaling molecule that is linking synaptic plasticity and energy metabolism. Neuroinflammation HFD-dependent negatively affects BDNF pathway and mitochondrial activity in the brain cortex. The effect is even more pronounced in the synaptic region, where the impaired energy supply may have a negative impact on neuronal plasticity.