Age-related changes in lumbosacral spinal nuclei that modulate continence and sexual function in C57BL/6 male mice

Tsang, Hayley Wing Sum (2015) Age-related changes in lumbosacral spinal nuclei that modulate continence and sexual function in C57BL/6 male mice. Doctoral thesis, Northumbria University.

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Abstract

Incontinence and sexual dysfunction are associated with human ageing. Skeletal muscles mediating bladder/bowel activity and reproductive function are innervated directly by lumbosacral spinal motoneurons (MNs) in the dorsolateral nucleus (DLN), spinal nucleus of bulbocavernosus (SNB). In addition, at the same spinal levels, autonomic modulation of these activities is mediated by the sacral parasympathetic nucleus (SPN). Age-related changes in these functions may be due to alterations in the ultrastructural morphology of MNs. An investigation on morphological changes was carried out in DLN-MNs of 4 and 32 month-old male C57BL/6 mice. There was an increase in lipofuscin-containing structures at 32 months. Rough endoplasmic reticulum, polyribosomes and mitochondria were prominent structures in the perinuclear region in 4 month-old DLN-MNs. By 32 months, lipofuscin dominated this region. Membranes of were generally slack in appearance. In addition, the nuclear membrane displayed deep invaginations. Previously published findings reported an age-related increase in synaptic contacts with SNB-MNs. Hence, image analysis of immunofluorescently labelled transverse sections from the lumbosacral spinal cord of 3-4.5, 12-13.5, 18, 24-25.5, and 30-31 month-old mice were studied to demonstrate the presence of age-related changes in CRF (corticotropin-releasing factor), VGLUT2 (vesicular glutamate transporter 2), 5-HT (5-hydroxytryptamine, or serotonin), and SP (substance P)-immunoreactive (ir) inputs in the number of somatic appositions and percentage area of immunoreactivity in the DLN, SNB, and SPN. There was no statistical significance between 3-4.5- and 30-31-months old in both parameters, except an increase in the number of 5-HT-ir and SP-ir somatic appositions on DLN- and SNB-MNs. When compared to 24-25.5 month, significant increases in the percentage area of VGLUT2-ir in the DLN and SNB were seen, while significant declines were seen in VGLUT2-ir somatic appositions to DLN-MNs and CRF-ir preganglionic neurons of the SPN. Declines in the percentage area of CRF and 5-HT immunoreactivity in the SPN and DLN, respectively, were found. A further immunohistochemical on markers of oxidative damage in DLN/SNB- MNs did not produce conclusive results. Together, this study demonstrated age-related changes that may contribute to alterations in maintaining continence and sexual functions in elderly animals. Such alterations may ultimately underpin the sexual dysfunction and incontinence seen in the aged human population.

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