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

点击翻译按钮获取中文摘要

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.