Novel brain networks influenced by ageing; effects on gene expression and synapses of diet-induced obesity.

肥胖目前是发达国家许多疾病和死亡的一个促成因素。医疗保健系统的负担将随着全球肥胖个体数量的预计大幅增加而扩大，特别是在发达国家（Ng等人，除了许多健康问题，如心脏并发症、癌症和糖尿病（Haslam & James，2005）之外;肥胖还与认知下降、突触功能障碍和脑容量损失有关（Alzoubi，Abdulaziz，& Alkadhi，2005;马萨等人，2010; Pistell等人，2010; Raji等人，2010年）。随着世界人口平均年龄的增长，肥胖对年龄的长期影响将变得更加明显，对所造成的认知功能障碍的调查将有助于了解大脑的衰老过程。某些研究表明，大脑老化可能反映了肥胖和限制卡路里摄入之间的连续性。热量限制可以增加寿命和改善认知（丰塔纳& Parkman，2015; Praag，Fleshner，Schwartz，& Mattson，2014），而肥胖可以导致寿命缩短和认知受损（Muller，Dietrich，阿西斯，Souza，& Portela，2013; Nguyen，Killcross，& Jenkins，2014）。肥胖也是发展与年龄相关的认知障碍的风险因素，例如中年而非老年的阿尔茨海默氏症（Hsu et al.，2016; Pedditizi，Peters，& Beckett，2016）.这表明衰老和肥胖之间存在复杂的相互作用，需要进一步研究。然而，到目前为止，还没有研究在测量突触活动和大脑基因表达的同时跟踪肥胖对寿命的影响。目前的研究旨在调查在6，12，18和24个月大时喂食高脂肪饮食的C57 BL/6小鼠肥胖的这些方面。在这些年龄，RNAseq将在一个半球上进行，而使用突触可塑性的现场记录的突触分析将在另一个半球上进行。当出现有趣的电生理结果时，将使用膜片钳对该分析进行改进。此外，从基因分析中鉴定的感兴趣的靶标可以在一些动物中使用免疫组织化学在蛋白质水平上进行随访。

Obesity is currently a contributing factor to many diseases and deaths in developed nations. The burden on health care systems will expand with large predicted increases in the number of obese individuals worldwide, especially in developed nations (Ng et al., 2014).In addition to a host of health problems such as cardiac complications, cancer and diabetes (Haslam & James, 2005); obesity is also linked to cognitive decline, synaptic dysfunction and brain volume loss ((Alzoubi, Abdulaziz, & Alkadhi, 2005; Massa et al., 2010; Pistell et al., 2010; Raji et al., 2010). As the average age of the world population increases, long term effects of obesity in relation to age will be become more apparent and investigation into the cognitive dysfunction caused will be helpful to understand the ageing process in the brain. Certain research suggests that brain ageing may reflect a continuum between obesity and restriction of calorie intake. Calorie restriction can lead to increased lifespan and improved cognition (Fontana & Partridge, 2015; Praag, Fleshner, Schwartz, & Mattson, 2014), while obesity can lead to decreased lifespan and impaired cognition (Muller, Dietrich, Assis, Souza, & Portela, 2013; Nguyen, Killcross, & Jenkins, 2014). Obesity is also a risk factor for developing age-related cognitive disorders such as Alzheimer's in middle but not old age (Hsu et al., 2016; Pedditizi, Peters, & Beckett, 2016). This suggests a complex interaction between ageing and obesity that requires further study. However, to date no study has followed the effects of obesity over the lifespan while measuring concurrent changes in synaptic activity and brain gene expression. The current study aims investigate these aspects of obesity in C57BL/6 mice fed a high-fat diet at 6, 12, 18 and 24 months of age. At these ages, RNAseq will be conducted on one hemisphere and synaptic analysis using field recording of synaptic plasticity will be conducted on the other. Where interesting electrophysiological results emerge this analysis will be refined with patch clamp. Additionally, interesting targets identified from gene analysis may be followed up at the protein level using immunohistochemistry in some animals.