Short-chain fatty acids, microbiota-gut-brain axis & hippocampal neurogenesis: a vehicle to learn techniques of dietary modulation of brain plasticity

许多以前的研究已经确定，认知(即记忆、注意力和反应时间等心理过程)会受到饮食的影响。然而，饮食调节认知的神经机制还不是很清楚。人类的海马体是大脑中与学习和记忆相关的一个区域。海马区是成人大脑中新生神经元形成的两个结构之一，被称为成人海马神经发生(AHN)。成年出生的海马神经元具有功能，并整合到海马神经元的回路中。大脑中的Ahn水平与学习和记忆直接相关。在整个生命周期中，ANN逐渐减少，伴随而来的是学习和记忆能力的受损。此外，与年龄相关的神经退行性疾病，如阿尔茨海默病和帕金森病，Ahn的减少也可以看到，这两种疾病都伴随着认知能力下降。虽然仍有许多事情需要从机制上解释，但有证据表明，饮食因素可以促进AHN。饮食可以通过卡路里摄入量、进餐频率、进餐质地和进餐内容来影响Ahn。因此，饮食对ANN的调节可能是营养影响认知功能的神经机制之一。短链脂肪酸(SCFA)是肠道中膳食纤维发酵产生的细菌代谢物，在肠道和大脑(微生物区系-肠道-脑轴)之间的通讯循环中发挥重要作用。然而，SCFAs影响认知的机制尚不清楚。最近的一项研究首次证明了SCFA可以促进Ahn(Yang等人。2020)。我们对单链脂肪酸对人AHN的调控机制知之甚少，这方面的研究人员也很少，这方面的知识和技能基础还存在很大差距。成人神经发生和精神健康实验室(伦敦国王学院，由Sandine Thuret博士领导)是全球领先的研究小组，研究Ahn的饮食调节，并使用一种新的Ahn体外模型。该奖项的目的是支持一名早期职业研究人员(ECR)完成关于体外细胞技术的集中和沉浸式培训，以调查饮食对AHN和认知的影响，并调查生理上相关的SCFA对AHN的影响。ECR目前是一名博士后研究员，她一直在使用以学校为基础的饮食干预研究来研究饮食对儿童和青少年认知功能的影响，她的工作跨越了学术界和食品行业。ECR将完成共同制作的、量身定做的10个阶段的培训计划，包括：1)基本细胞培养培训；2)细胞实验设计培训；3)海马祖细胞(HPC)培养培训；4)建立细胞库的培训；5)HPC增殖培训；6)HPC分化培训；7)免疫细胞化学培训；8)显微镜培训；9)高含量成像培训和10)数据分析培训。这一奖项将发展跨学科技能，并深入了解饮食可能影响认知的潜在神经机制。这将使该奖项以外的关于饮食对认知的影响的多学科研究得以完成，这可能导致对人类营养及其在人群认知健康中的作用的洞察。培训奖将加强ECR在实验室营养技术方面的知识和技能，以补充他们在人类饮食干预研究中的实地培训。这是一个新的研究领域，值得进一步关注，因为更好地了解营养影响认知健康的神经机制可能会导致新的饮食方法，以对抗与年龄相关的认知衰退、神经退行性疾病，并促进健康老龄化。

Numerous previous studies have firmly established that cognition (i.e. mental processes such as memory, attention, and reaction time) is influenced by diet. However, the neural mechanisms by which diet modulates cognition are not well understood. The human hippocampus is an area of the brain associated with learning and memory. The hippocampus is one of the two structures in the adult brain where the formation of newborn neurons, known as adult hippocampal neurogenesis (AHN) persists. Adult-born hippocampal neurons are functional and integrated into the hippocampal circuitry. The level of AHN in the brain has been linked directly to learning and memory. Across the lifespan, a progressive reduction of AHN and concomitant impaired learning and memory abilities occurs. Furthermore, a reduction in AHN is seen in age-related neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, both of which are accompanied by cognitive decline. Whilst much remains to be explained mechanistically, there is evidence that dietary factors can promote AHN. Diet can influence AHN through calorie intake, meal frequency, meal texture, and meal content. Therefore, modulation of AHN by diet is a possible neural mechanism by which nutrition impacts on cognitive function. Short-chain fatty acids (SCFAs) are bacterial metabolites produced by fermentation of dietary fibre in the gut that play an important role in the communication loop between the gut and the brain ('the microbiota-gut-brain axis'). However, the mechanisms through which SCFAs influence cognition are unclear. A recent study demonstrated for the first time that SCFAs can promote AHN (Yang et al. 2020). We know little about the modulatory mechanisms of human AHN via SCFAs and there are few skilled researchers in this field, which leaves a large gap in the knowledge and skill base. The Adult Neurogenesis and Mental Health laboratory (Kings College London; led by Dr Sandrine Thuret) are the leading research group globally on dietary modulation of AHN and use a novel in vitro model of AHN. The aim of this award is to support the completion of focussed and immersive training of an early career researcher (ECR) on the in vitro cellular techniques required to investigate the impact of diet on AHN and cognition and to investigate the impact of physiologically relevant SCFAs on AHN. The ECR is currently a postdoctoral researcher who has been working on the effects of diet on cognitive function in children and adolescents using school-based dietary intervention studies and her work has spanned both academia and the food industry. A co-produced, tailored, 10-stage training plan will be completed by the ECR including: 1) Basic cell culture training; 2) Cellular experimental design training; 3) Hippocampal progenitor cells (HPC) culture training; 4) training in making a cell bank; 5) HPC Proliferation training ; 6) HPC Differentiation training; 7) Immunocytochemistry training 8) Microscopy training; 9) High content imaging training and 10) Data analyses training. This award will develop cross-disciplinary skills and a deep understanding of the underlying neural mechanisms by which diet could influence cognition. This will enable to completion of multi-disciplinary research beyond this award on the effects of diet on cognition, which could lead to insights into human nutrition and its role in the cognitive health of the population. The training award will strengthen the ECR's knowledge and skills in lab-based nutrition techniques to complement their field-based training in human dietary intervention studies. This area of investigation is new and warrants further attention because a better understanding of the neurological mechanisms by which nutrition affects cognitive health may lead to novel dietary approaches to combat age-associated cognitive decline, neurodegenerative diseases, and promote healthy ageing.