Age-related changes in CNS and PNS neuronal structures within C57BL / 6J male mice that regulate continence

Doogan, Emily (2020) Age-related changes in CNS and PNS neuronal structures within C57BL / 6J male mice that regulate continence. Doctoral thesis, Northumbria University.

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Abstract

The prevalence of urinary incontinence (UI), faecal incontinence (FI) and chronic constipation increases with age. Sufferers tend to have reduced quality of life, with treatments being far from ideal. Furthermore, treatment costs place significant financial burden on the economy. The lumbosacral somatic dorsolateral nucleus (DLN) and spinal nucleus of the bulbospongiosus (SNB), and the sacral parasympathetic nucleus (SPN), exert control over the external urethral sphincter (EUS) external anal sphincter (EAS), and bladder detrusor / colorectal smooth muscle, respectively. Pontine nuclei, including the pontine micturition centre (PMC), locus coeruleus (LC) and laterodorsal tegmental nucleus (LDTg), and the hypothalamic paraventricular nucleus (PVN) share connection pathways and exert control over defaecation and micturition.
In this work, lumbosacral spinal structures were immunolabelled alongside inhibitory methionine-enkephalin (met-ENK) and gamma aminobutyric acid (GABA) boutons; pontine structures were immunolabelled alongside inhibitory met-ENK boutons; and the PVN was immunolabelled alongside inhibitory GABA and excitatory glutamate. The density of GABA and met-ENK in the SPN significantly decreased with age; the density of glutamate significantly increased in the PVN periventricular region (PVNpv); and the number of GABA inputs onto OXY+ and VP+ parvocellular soma within the PVN medial parvocellular dorsal division (PVNmpd) significantly increased with age. In all other nuclei the density / number of inputs from immunolabelled boutons remained unchanged with age. Furthermore, soma size and cell number (observed in pontine and spinal nuclei) were maintained with age. The distal colon (DC) is also extensively controlled by the intrinsic enteric nervous system (ENS) which is known to be subject to age-related structural changes. Protein was extracted from the whole DC with the future aim of extracting proteins specifically from the myenteric plexus (MP). Subsequently, whole DC protein extract was subject to downstream protein analysis to determine expression changes with age. Forty-four proteins showed age-associated change in regulation. These findings indicate that age-associated changes occur at all levels of nervous and non-nervous structures that may contribute to age-related voiding dysfunctions.

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