| Dissertation |
Thesis (Ph.D.) --NUI, 2013 at Department of Anatomy and Neuroscience, UCC. |
| Summary |
The development of the peripheral nervous system (PNS) is an intricately orchestrated series of events encompassing processes such as neurogenesis, neurite growth and target innervation. The growth of axons to their targets is dependent on numerous locally acting and diffusible signalling molecules. Identifying and characterising these molecules is crucial to understand the formation and maintenance of appropriate neural connections between neurons and their targets and allows us to grasp the molecular basis of how “connectivity” is established. Interleukin-1beta (IL-1β) and tumour necrosis factor-alpha (TNF-α) are two pro-inflammatory cytokines which activate nuclear factor-kappaB (NF-κB). It is already established that sympathetic axonal growth is inhibited during the perinatal period by NF-κB activation. To that end, this PhD thesis aims to elucidate if IL-1β and TNF-α are physiological ligands which may restrict sympathetic innervation via NF-κB activation during normal development in vivo. IL-1β significantly inhibited growth and branching from sympathetic neurons in vitro during a stage in development when their axons are ramifying within their targets in vivo. IL-1β also acted directly on axon terminals to inhibit their growth, suggesting that it may act locally. IL-1β-mediated growth inhibition was abolished by an NF-κB signalling inhibitor, confirming that the effects were being mediated via NF-κB. Lipopolysaccharide-induced maternal inflammation was then used to examine if IL-1β upregulation during the perinatal period in vivo affected foetal target innervation and revealed that gastrointestinal sympathetic innervation was impaired. Interestingly, TNF-α was significantly upregulated in foetal neurons in vivo following maternal inflammation. Therefore, the effects of TNF-α on P1 rat sympathetic neurons in vitro were examined. Similar to IL-1β, TNF-α inhibited neurite growth and branching via NF-κB and this effect was restricted to the perinatal period. These findings suggest that maternal inflammation during late gestation can result in foetal target innervation deficits via NF-κB signalling mediated by TNF-α upregulation. |
| Subject |
Inflammation -- Immunological aspects.
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Cytokines.
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| Collection |
Theses Ph.D.
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Theses Anatomy and Neuroscience Department
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| Description |
204 p. ; 30 cm. |
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