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Mechanisms underlying the role of gut-microbiota in exercise-induced changes in cognitive function in middle-age

Middle age is a critical time for cognitive changes that may precede dementia onset. Interestingly, studies have shown that lifestyle factors such as exercise can reverse age-related cognitive decline and improve memory function. However, the underlying mechanisms that underpin these effects are unknown. Besides a decline in physical fitness, middle age is characterized by extensive change in gastrointestinal function, gut microbiota composition, and related metabolites.

Mechanisms underpinning the interplay between chronic neuroinflammation and exercise on cognitive function during middle age

During middle age, accumulating neuroinflammation threatens cognitive capacity and negatively affects hippocampal neurogenesis, a process important for cognitive function. Physical exercise promotes neurogenesis and may delay cognitive decline. This project investigates convergent proteomic and metabolic processes dysregulated in the hippocampus and systemic milieu during middle age and in response to exercise. Results will identify predictors of cognitive decline that are modifiable by exercise.

Gut microbes, Neuroinflammation and Alzheimer's disease: determining the immunoregulatory role of gut microbiota on brain and behaviour

In this project we showed that transplantation of faecal microbiota from Alzheimer's patients into microbiota-depleted young adult rats induced impairments in behaviours reliant on adult hippocampal neurogenesis, an essential plasticity process for certain memory functions and mood. The severity of impairments correlated with clinical cognitive scores in donor patients. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera.

Investigating sex-specific influences of gut microbiome on Alzheimer’s disease (SIGMA)

Women are twice as likely as men to develop Alzheimer’s disease, particularly in later life. While hormonal differences between biological sexes have been suggested as a potential explanation for this disparity, the exact reasons remain unclear. Recently, the gut microbiome has emerged as a key area of interest in Alzheimer’s research due to its role in disease progression and observed differences between males and females.

Investigation of the benefits of exercise in Alzheimer’s disease: focus on the microbiota- gut-brain axis

It is well established that there is elevated inflammation in Alzheimer’s disease, while hippocampal neurogenesis (a type of brain plasticity) is decreased in the brains of Alzheimer’s patients. Research has shown that gut microbiota may be a master regulator of both inflammation and neurogenesis, and emerging research suggests a key role of the microbiota-gut-brain axis in Alzheimer’s development. Thus, targeting the microbiota may be a new avenue to develop knowledge for Alzheimer’s treatment.

Lifestyle interventions to Prevent cOgnitive deficits in subjects With depressive symptoms: from mEchanisms to clinical pRactice (POWER)

POWER will identify the immune-metabolic and nutritional signatures associated with cognitive impairment in ageing and depression. A clinical trial investigating effects of diet, physical activity, and brain training on cognition and depressive symptoms will be conducted. The role of gut microbiota in mediating the beneficial effects of these interventions on cognitive outcomes, depressive symptoms, hippocampal neurogenesis and inflammation will then be conducted in an animal model.

Food4PD: Validation of a novel functional food designed to meet the nutritional needs of People living with Parkinson’s

Constipation is a common complication and non-motor symptom of Parkinson’s disease (PD) and affects up to 80% of people with PD. It is in fact within the non-motor symptoms that nutrition and dietetic intervention could have the greatest impact. Research suggests that increasing the amount of fibre in the diet could help to alleviate the effects of constipation. Inulin is a type of fibre widely found in a variety of vegetables, and recent studies have shown that inulin can improve constipation in people with PD.

Development of Novel Oligogenic ALS Models for Drug Discovery

Amyotrophic Lateral Sclerosis (ALS) is a fatal disease resulting in muscle weakness, paralysis and ultimately death, often within 2-3 years of symptom onset. These symptoms arise due to the loss of motor neurons from the brain and spinal cord. Treatment options are limited and have little impact on halting progression of the disease. This research project is aimed at developing and characterising new models of ALS that can be used to investigate how motor neurons degenerate in people living with ALS.

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