Changes in immunoreactive terminals containing serotonin, substance P, vesicular glutamate transporter 2 and corticotropin-releasing factor in the lumbosacral spinal cord of aged C56BL/6J male mice.

Tsang, Hayley; Zhang, Meng; Black, Gary W.; Saffrey, M. Jill and Ranson, Richard N. (2014). Changes in immunoreactive terminals containing serotonin, substance P, vesicular glutamate transporter 2 and corticotropin-releasing factor in the lumbosacral spinal cord of aged C56BL/6J male mice. In: Conference proceedings of British Society for Research on Ageing 64th Annual Meeting 'Exercise, Activity and Ageing Mechanisms', article no. 39.

Abstract

The muscles that mediate sphincter closure and copulatory behaviour are innervated by spinal motoneurons (MNs) located within the dorsolateral nucleus (DLN), spinal nucleus of the bulbocavernosus (SNB), and sacral parasympathetic nucleus (SPN). In aged rats, the number of synapses contacting these MNs is reduced. Similar data for mice is lacking. Hence, the current study sought to identify age-related changes in terminals containing serotonin (5-HT), substance P (SP) and glutamate (identified by vesicular glutamate transporter 2, VGLUT2) in the DLN and SNB of male C57BL/6 mice. Terminals located in the SPN containing corticotropin-releasing factor (CRF), a neuropeptide involved in facilitating voiding behaviour, were also studied. Spinal cord sections from 3-4.5, 24 and 30-31 months mice were immunofluorescently labelled for the neuronal markers MAP2 or ChAT, in combination with 5-HT, SP, VGLUT2 or CRF. In 3-4.5 months mice, labelling for immunoreactive (IR) terminals appeared uniform in signal intensity, size and distribution. By contrast, IR terminals from 24+ months mice varied in intensity and size. Some IR terminals that were enlarged, and irregular in shape, were observed. This was most apparent for 5-HT inputs to SNB MNs. Ultrastructural studies are also being undertaken to determine the synaptic connectivity of 5-HT-, SP- and VGLUT2-IR terminals. These studies will provide insight into structural alterations of MNs, innervating muscles that promote sphincter closure and mediate sexual behaviours, and how these changes may contribute to disrupted muscle contraction in relation to ageing.

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