Exercise and cell therapy: restorative mechanisms for reversing age-related memory decline

Memory problems in late life are extraordinarily common, ranging from mild episode memory complaints to the more severe memory impairment associated with dementia and neurodegenerative diseases. Physical exercise in both animals and humans have emerged as potential interventions for the prevention of age-related cognitive decline found in old age, as well as enhancing learning and memory in adults. However, the mechanisms underlying such prevention remain poorly understood. Stem cell therapy is a potential restorative intervention for cognitive decline but many fundamental questions regarding this intervention remain unexplored. A series of experiments investigated the role of exercise in a variety of hippocampally-dependent and hippocampally-independent behavioural tasks in both young and aged rat populations. Chapter 2 observed an age-related cognitive difference in a spatial learning maze and a object and place recognition memory task. Results found that episodic place recognition memory was particularly sensitive to age-related decline but object place recognition memory was intact throughout the lifespan. Chapter 2 additionally examined whether exercise can rescue long term memory deficits in the place and object recognition paradigms in young and aged animals. Results produced differential effects, such that exercise rescued place memory in aged rats and object memory in young rats. Chapter 3 further investigated the effects of exercise in the reversal of this cognitive deficit. Place recognition memory was rescued with physical exercise in aged rats, and had no discernible effect in young rats for either task. Furthermore, this behavioural improvement was linked specifically to synaptic density but not neurogenesis. Finally, Chapter 4 assessed the intervention of cell therapy treatment in aged rats, and found that transplanted cells survived, differentiated and promoted cognition. Additionally, when cell transplant was coupled with exercise, both interventions were found to rescue cognition, but a combined approach resulted in a significant increase in synaptic strength in the hippocampus of aged animals. In conclusion, normal ageing is associated with impairments in cognitive function and are linked to specific and relatively subtle synaptic alterations in the hippocampus. However, these deficits can be rescued and enhanced with therapeutic strategies of exercise and cell therapy