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Nerve-target interactions in the mature and aged peripherial nervous system

Thrasivoulou, Christopher; (1998) Nerve-target interactions in the mature and aged peripherial nervous system. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Abstract

This study has centred on neuronal ageing in the autonomic and peripheral nervous system with particular reference to the instructive role that target tissues may have in regulating neuronal phenotype. Previous work in our laboratory has demonstrated a significant decrease in the total population of sympathetic, sensory and parasympathetic nerves innervating cerebral blood vessels (CBV) and eccrine sweat glands using the pan-neuronal marker, protein-gene-product 9.5, in the aged rat. This study investigates the subpopulations of nerves that innervate these targets using novel techniques in an attempt to identify which group/s are affected in old age and then goes on to study the underlying mechanisms of age-related changes. Morphometric assays were developed using confocal and light microscopy and image analysis which could reliably and repeatedly detect changes in nerve density, transmitter expression and other aspects of neuronal phenotype. Critical areas of technique were identified. These techniques demonstrated significant age-related decreases in the innervation of (CBVs) by the sympathetic and sensory populations as demonstrated by tyrosine hydroxylase (TH) and calcitonin gene-related protein (CGRP) or neurofilament (NF-R39) immunostaining, respectively. There was a large reduction (70%) in numbers of trigeminal sensory neurons projecting to the middle cerebral artery (MCA) in old compared to young rats. Moreover, the number of traced neurones which were CGRP/NF-R39 positive were also reduced (80%) in old trigeminal ganglia compared to young, either as a result of age-related changes in retrograde axon transport or by neuronal cell death. In oculo transplantation was then used to discover whether target tissues regulate these age-changes in sympathetic and sensory nerve growth and whether they influence changes in neurotransmitter phenotype. Sympathetic nerve density as well as neurotransmitter phenotype was found to be regulated by the target tissue and not by intrinsic differences of the neurons. Nerve growth factor (NGF) induced nerve growth onto aged implants to levels over and above that found in young implants. Target tissues appeared able to influence the extent of their sensory innervation, although the pattern and density of innervation was atypical following in oculo transplantation. Following surgical sympathectomy, NF-R39 sensory nerve density showed significant increases in young middle cerebral artery (MCA), perhaps as a result of the increased pool of available NGF. Finally, double-immunohistochemistry was used to assess expression of the low affinity NGF receptor (p75) colocalised with sympathetic and sensory nerves. Changes in p75 expression were found to mirror the decline in sympathetic and sensory nerves with age. The component of p75 staining which was not colocalised with sympathetic and sensory nerves was not altered in old age.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Nerve-target interactions in the mature and aged peripherial nervous system
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Peripheral nervous system
URI: https://discovery.ucl.ac.uk/id/eprint/10103345
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