The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells

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dc.contributor.advisor Nolan, Yvonne M. en Ryan, Sinead Maria 2014-01-28T10:38:05Z 2013 2013
dc.identifier.citation Ryan, S. M. 2013. The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells. PhD Thesis, University College Cork. en
dc.description.abstract Neurogenesis occurs in two distinct regions of the adult brain; the subgranular zone (SGZ) of the dentate gyrus (DG) in the hippocampus, and the subventricular zone (SVZ) lining the lateral ventricles. It is now well-known that adult hippocampal neurogenesis can be modulated by a number of intrinsic and extrinsic factors e.g. local signalling molecules, exercise, environmental enrichment and learning. Moreover, levels of adult hippocampal neurogenesis decrease with age, at least in rodents, and alterations in hippocampal neurogenesis have been reported in animal models and human studies of neuropsychiatric and neurodegenerative conditions. Neuroinflammation is a common pathological feature of these conditions and is also a potent modulator of adult hippocampal neurogenesis. Recently, the orphan nuclear receptor TLX has been identified as an important regulator of adult hippocampal neurogenesis as its expression is necessary to maintain the neural precursor cell (NPC) pool in the adult DG. Likewise, exposure of animals to voluntary exercise has been consistently demonstrated to promote adult hippocampal neurogenesis. Lentivirus (LV)- mediated gene transfer is a useful tool to elucidate gene function and to explore potential therapeutic candidates across an array of conditions as it facilitates sustained gene expression in both dividing and post-mitotic cell populations. Both intrinsic and extrinsic factors are important regulators of adult hippocampal neurogenesis. Examining how these factors are affected by an inflammatory stimulus, and the subsequent effects on adult hippocampal neurogenesis provides important information for the development of novel treatment strategies for neuropsychiatric and neurodegenerative conditions in which adult hippocampal neurogenesis is impaired. The aims of the series of experiments presented in this thesis were to examine the effect of the pro-inflammatory cytokine interleukin-1β (IL-1β) on adult hippocampal NPCs both in vitro and in vivo. In vitro, we have shown that IL-1β reduces proliferation of adult hippocampal NPCs in a dose and time-dependent manner. In addition, we have demonstrated that TLX expression is reduced by IL-1β. Blockade of IL-1β signalling prevented both the IL-1β-induced reduction in cell proliferation and TLX expression. In vivo, we examined the effect of short term and long term exposure to LV-IL-1β in sedentary mice and in mice exposed to voluntary running. We demonstrated that impaired hippocampal neurogenesis is only evident after long term exposure to IL-1β. In mice exposed to voluntary running, hippocampal neurogenesis is significantly increased following short-term but not long-term exposure to running. Moreover, short-term running effectively prevents any IL-1β-induced effects on hippocampal neurogenesis; however, no such effects are seen following long-term exposure to running. en
dc.description.sponsorship Science Foundation Ireland (SFI/RFP/NSC1298) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2013, Sinead M. Ryan. en
dc.rights.uri en
dc.subject Interleukin-1beta en
dc.subject Hippocampal neurogenesis en
dc.subject Inflammation en
dc.subject TLX en
dc.subject Exercise en
dc.subject Neural precursor cell en
dc.subject Lentivirus en
dc.subject.lcsh Neurons--Growth en
dc.subject.lcsh Hippocampus (Brain) en
dc.title The role of the IL-1 type 1 receptor in the life, death and differentiation of adult hippocampal neural precursor cells en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Medicine and Health) en
dc.internal.availability Full text not available en Indefinite en 10000-01-01
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Anatomy en
dc.check.reason This thesis is due for publication or the author is actively seeking to publish this material en
dc.check.opt-out No en
dc.thesis.opt-out false
dc.check.chapterOfThesis 8
dc.check.embargoformat Both hard copy thesis and e-thesis en
dc.internal.conferring Autumn Conferring 2013 en

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© 2013, Sinead M. Ryan. Except where otherwise noted, this item's license is described as © 2013, Sinead M. Ryan.
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