The Effects of Ageing on the Spinal Neurones Controlling Micturition and Continence

In humans, the prevalence of urinary incontinence increases with old age. This condition has a major impact on the quality of life of elderly people, and is associated with anxiety, depression, social embarrassment, interrupted sleep and financial burden. The main goal of the research presented in this thesis was to examine potential changes in neuronal circuitry underlying urinary incontinence to increase our understanding of the pathophysiology of urinary incontinence in ageing, using the mouse as a model. Measuring the micturition characteristics of 3, 24 and 32 month old mice revealed that increasing age increases the frequency of micturition, total volume of urine produced and volume/void in night and daytime experiments. In addition, 32 month old mice had a shorter interval between voids than the younger animals. To better understand the spinal cord circuitry involved in regulating micturition, the location and structure of the dorsolateral nucleus (innervating the external urethral sphincter) in mouse spinal cord were determined using retrograde labelling techniques and immunohistochemistry for a marker for cholinergic neurones, choline acetyltransferase (ChAT). The DLN was found to be localised in L6-S1 of mouse spinal cord. The nature of the inputs onto retrogradely labelled (by injection of Fluorogold) dorsolateral nucleus neurones and autonomic neurones in the spinal cord which control micturition were also determined using immunohistochemistry to detect excitatory (glutamatergic) and inhibitory (GABA and glycinergic) terminals in 3, 24 and 32 month old mice. This revealed that during ageing there is a net decrease of excitatory and increase in inhibitory inputs onto DLN, sympathetic and parasympathetic preganglionic neurones. The shift in the balance of excitatory-inhibitory presynaptic inputs to these neurones provides new insight to the mechanism of urinary incontinence in ageing.