Differential susceptibility to ageing of rat preganglionic neurones projecting to the major pelvic ganglion and of their afferent inputs
Introduction
In small rodents, the majority of postganglionic autonomic neurones supplying the male pelvic viscera are located in a large ganglion, the major pelvic ganglion (MPG), located on the lateral surface of the prostate gland. This is equivalent to the more diffuse plexus that contains the postganglionic autonomic neurones supplying the pelvic viscera of larger mammals. The MPG is also unusual among autonomic ganglia in that it contains both parasympathetic and sympathetic postganglionic neurones and provides a useful model system in which comparisons of changes in the two efferent pathways of the autonomic nervous system can be made. In recent years, work in our laboratory has demonstrated that the population of sympathetic neurones in the male rat MPG is selectively affected by ageing while the parasympathetic population is largely spared. For example, neuronal somata in the MPG that express sympathetic markers such as tyrosine hydroxylase and neuropeptide Y, and their terminals in target organs, are decreased in number in aged animals Warburton and Santer, 1993, Warburton and Santer, 1994. By contrast, cells expressing markers for postganglionic parasympathetic neurones, such as the enzymes acetylcholinesterase and NADPH-diaphorase, showed no significant changes. The number of neurones per unit area in the MPG was also reduced with age, a factor that may be partly attributable to changes in the composition and extent of the extracellular matrix (Warburton and Santer, 1997). However, the effects of ageing on the absolute numbers of sympathetic and parasympathetic neurones of the MPG have yet to be determined. Immunocytochemical studies using antibodies against synapsin I have revealed that synaptic boutons on postganglionic sympathetic neurones in MPG are significantly reduced in number in aged rats while those on postganglionic parasympathetic neurones are not (Warburton and Santer, 1995). The majority of the synaptic boutons in the MPG obviously derive from preganglionic neurones, but it is likely that axonal collaterals from sensory neurones and terminals from sympathetic postganglionic neurones in the inferior mesenteric ganglion also contribute to the total number of synapses received by the parasympathetic population.
Given the well established trophic relationships between synaptically connected neurones, the observed age-related differences in the synaptic input received by sympathetic and parasympathetic neurones within the aged MPG suggest that similar effects may be acting on populations of preganglionic neurones that project to the ganglion. We have therefore begun a detailed investigation of the affects of age on the number and morphology of spinal preganglionic neurones that project to the MPG employing retrograde tracing methods to identify these neurones. This has revealed a significant pruning of the dendritic arbours (manifested as a decline in the total dendritic length and number of branch points) in sympathetic, but not parasympathetic, preganglionic neurones Dering et al., 1996, Dering et al., 1998. In order to investigate the possible causes of this phenomenon, we are currently investigating age-related changes in the distribution of synapses received by the preganglionic neurones. Using antibodies against the neurotransmitters of descending pathways and local spinal network neurones, we are analysing age-related changes in the circuitry controlling the preganglionic neurones. This may provide some insight into whether trophic influences from spinal interneurones play a role in the integrity and survival of autonomic neurones controlling the lower pelvic viscera.
Section snippets
Material and methods
Male Wistar rats of 3–4 months (young adults) and 24+ (aged) months from a colony raised in semi-barrier conditions were used in all the studies. All rats involved in surgical procedures were given 1% Vetergesic (buprenorphine hydrochloride, Reckitt & Coleman Products, Hull, UK) in their drinking water 24 h before surgery and throughout the recovery period. Anaesthesia was induced with 5% Halothane (Rhone Mérieux, Harlow, UK—4% for aged animals) in 100% oxygen and maintained by 3% Halothane
Morphology of preganglionic neurones
Although this study did not include a quantitative investigation of preganglionic neuron numbers, there appeared to be considerably fewer sympathetic neurones in the central autonomic and intermediolateral regions of the L1 and L2 cord of aged rats compared to the young group. Confocal microscope studies revealed that the aged preganglionic sympathetic neurones often had swollen or misshapen somata as well as fewer dendrites, which were shorter and had fewer branch points. The preganglionic
Discussion
In order to assess the significance of age-related changes in the distribution of amino-acid immunoreactive synapses on preganglionic neurones, it is important to consider the likely origins of the neurones whose axons they represent. Immunocytochemical studies of the lumbar spinal cord have demonstrated that cell bodies immunoreactive for the inhibitory transmitters GABA and glycine are abundant in most spinal laminae with the exception of laminae VIII and IX, and that the two transmitters are
Acknowledgements
This work was supported by a Research Into Ageing Prize Studentship (MAD), a BBSRC postgraduate studentship (HNW) and a BBSRC SAGE grant 72/SAG09911 (AHDW, RMS, RNR).
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2015, Handbook of Clinical NeurologyCitation Excerpt :For example, immunohistochemical analyses in aged rats revealed significant age-associated declines in the serotonergic (5-HT) and adrenergic innervation of various spinal cord regions, including the intermediolateral cell nucleus, sacral parasympathetic nucleus, dorsal gray commissure, and in the area of the ventral horn that contains Onuf's nucleus, although 5-HT innervation of the sacral parasympathetic nucleus and tyrosine hydroxlase-like immunoreactivity in the ventral horn nucleus were maintained (Ranson et al., 2003). Sympathetic PGNs in the L1–2 spinal cord that project to the major pelvic ganglion also exhibit a number of age-related degenerative changes, such as reductions in the cell number, the length of their dendrites, and the synaptic contacts made by glutamate-immunoreactive boutons on to the dendrites, although these changes are not seen in parasympathetic PGNs in the L6–S1 spinal cord (Santer et al., 2002). Frequent voiding produced by apomorphine-induced dopamine receptor activation is more pronounced in aged rats compared with young rats, suggesting that aged rats are more susceptible to altered central neurotransmitter mechanisms that induce bladder overactivity, even though baseline bladder function declines with aging (Chai et al., 2000).
The soma and proximal dendrites of sympathetic preganglionic neurons innervating the major pelvic ganglion in female rats receive predominantly inhibitory inputs
2012, NeuroscienceCitation Excerpt :F-type boutons, for example, have been shown to exhibit immunoreactivity for GABA and/or glycine in the cat ventral horn, thus suggesting that boutons with flat, pleomorphic vesicles are most likely inhibitory (Örnung et al., 1994, 1996). Previous studies have detected the presence of GABA and glycine in boutons in apposition with thoracolumbar SPNs in male rats (Santer et al., 2002). Past studies combining electron microscopy with immunohistochemistry have also demonstrated that the excitatory transmitter, glutamate, has a strong correlation with ultrastructural characteristics such as clear, spheroid synaptic vesicles (Broman et al., 1993; Shupliakov et al., 1993; Örnung et al., 1998; Persson and Broman, 2004).