Johnson, Richard James Ramsay; (1998) Plasticity in adult autonomic neurons. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

This thesis has examined neuronal plasticity in autonomic neurons in both the mature and ageing peripheral nervous system. By examining the growth and survival responses of rat enteric neurons in both the aging process and as a response to changes in their environment, I have tried to identify some of the factors which influence such responses. Initially, several established immunohistochemical and histochemical techniques were used to examine the rodent enteric nervous system (ENS). Quantitative methods were established to count the overall number of autonomic neurons in the ENS through a number of age stages. The possibility that particular neuronal phenotypes were vulnerable to cell death was examined using a range of different markers. Data from this initial study contradicted previous findings by concluding that there was very little evidence for loss of any neuron type in the myenteric plexus of the aged Sprague Dawley rat. In contrast to earlier studies made on ad libitum fed animals, our aged rats had been kept on a restricted diet, which has been shown to enhance the longevity of small laboratory animals. The mechanism by which it does so is unknown. Several aspects of ENS morphology were therefore examined in Sprague Dawley rats maintained on ad libitum and restricted diets for different time periods. The most striking observation was that aged (24M) animals fed ad libitum showed large scale death of their myenteric neurons, in contrast to animals of a similar age fed on a restricted diet, which showed maintained numbers of enteric neurons. The effect of restricted diet extended through to 30M of age. It was determined that cell death commenced at approximately 16 months in ad libitum fed rats. To investigate the mechanisms underlying cell death, I examined the occurrence of programmed cell death (apoptosis) in the ENS, changes in expression of the low affinity neurotrophin receptor, p75, in the ENS and altered levels of free radicals, all of which are implicated in neurodegeneration elsewhere in the nervous system. Some adult neurons are able to grow in response to changes in their target tissues. The induction of hypertrophy in vivo in the small intestine (a possible consequence of feeding regime) was used to examine the capacity for compensatory growth in associated autonomic neurons. Differential changes within neuronal subtypes were observed. The work I present in this thesis has identified some of the factors which may influence different aspects of neuronal plasticity in maturity, and has determined that increased functional demands and dietary conditions may contribute significantly to altered plasticity in the adult and ageing autonomic nervous system.

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