The Investigation of Age-related Changes in Apathy-related Behaviour and Biological Rhythms

Abstract

Apathy is a multidimensional psychiatric syndrome that often occurs alongside neurodegenerative disease but also otherwise healthy ageing. Despite its clinical importance, little is known about its underlying mechanism in normal ageing. Ageing is associated with disrupted biological rhythms, which can have a significant impact on health, including the development of psychiatric disease. The development of a rodent model for apathy could allow for its underlying neurobiology to be investigated and for specific treatments to be developed. Improving our understanding of changes to the aged circadian system could allow for a potential relationship between apathy and disrupted biological rhythms to be tested in the future. This thesis therefore investigates the effects of ageing on apathy-related behaviour and biological rhythms in rodents.
Apathy-related behaviour was assessed in mice using a battery of behavioural tests and physiological measures that map onto human apathy domains. It was found that aged mice show behaviours relevant to multiple domains of apathy. To account for potential species differences and to explore more complex behaviours, apathy-related behaviour was assessed in aged rats. Aged rats did not show the same deficits as aged mice, revealing striking species differences. Under ad libitum feeding conditions aged rats showed blunted circadian activity and corticosterone release but not core body temperature suggesting a system-specific disruption. Feeding in the light phase disrupted normal nocturnal activity to a greater extent in aged versus young rats, suggesting that feeding time may be a stronger zeitgeber than light in aged rats. Aged mice showed a weaker activity circadian rhythm driven by a reduction in activity immediately following lights off.
This thesis provides evidence that aged mice may be a suitable apathy model and both rats and mice show some evidence of biological rhythm disruption. Future work should test a relationship between the two for potential therapeutic benefit.

Date of Award	25 Jan 2022
Original language	English
Awarding Institution	University of Bristol
Supervisor	Emma S J Robinson (Supervisor) & Stafford L Lightman (Supervisor)