A study of diet and health in the elderly; the gut microbiota as a source of bioactive agents

The global proportion of older persons is increasing rapidly. Diet and the intestinal microbiota independently and jointly contribute to health in the elderly. The habitual dietary patterns and functional microbiota components of elderly subjects were investigated in order to identify specific effector mechanisms. A study of the dietary intake of Irish community-dwelling elderly subjects showed that the consumption of foods high in fat and/or sugar was excessive, while consumption of dairy foods was inadequate. Elderly females typically had a more nutrient- dense diet than males and a considerable proportion of subjects, particularly males, had inadequate intakes of calcium, magnesium, vitamin D, folate, zinc and vitamin C. The association between dietary patterns, glycaemic index and cognitive function was also investigated. Elderly subjects consuming ‘prudent’ dietary patterns had better cognitive function compared to those consuming ‘Western’ dietary patterns. Furthermore, fully-adjusted regression models revealed that a high glycaemic diet was associated with poor cognitive function, demonstrating a new link between nutrition and cognition. An extensive screening study of the elderly faecal-derived microbiota was also undertaken to examine the prevalence of antimicrobial production by intestinal bacteria. A number of previously characterised bacteriocins were isolated (gassericin T, ABP-118, mutacin II, enterocin L-50 and enterocin P) in this study. Interestingly, a Lactobacillus crispatus strain was found to produce a potentially novel antimicrobial compound. Full genome sequencing of this strain revealed the presence of three loci which exhibited varying degrees of homology with the genes responsible for helveticin J production in Lb. helveticus. An additional study comparing the immunomodulatory capacity of ‘viable’ and ‘non-viable’ Bifidobacterium strains found that Bifidobacterium-fermented milks (BFMs) containing ‘non-viable’ cells could stimulate levels of IL-10 and TNF-α in a manner similar to those stimulated by BFMs containing ‘viable’ cells in vitro.

Investigations into the cellular and molecular changes in the amygdala in models of temporal lobe epilepsy and maternal immune activation

The amygdala is a limbic structure that is involved in many of our emotions and processing of these emotions such as fear, anger and pleasure. Conditions such as anxiety, autism, and also epilepsy, have been linked to abnormal functioning of the amygdala, owing to improper neurodevelopment or damage. This thesis investigated the cellular and molecular changes in the amygdala in models of temporal lobe epilepsy (TLE) and maternal immune activation (MIA). The kainic acid (KA) model of temporal lobe epilepsy (TLE) was used to induce Ammon’s-horn sclerosis (AHS) and to investigate behavioural and cytoarchitectural changes that occur in the amygdala related to Neuropeptide Y1 receptor expression. Results showed that KA-injected animals showed increased anxiety-like behaviours and displayed histopathological hallmarks of AHS including CA1 ablation, granule cell dispersion, volume reduction and astrogliosis. Amygdalar volume and neuronal loss was observed in the ipsilateral nuclei which was accompanied by astrogliosis. In addition, a decrease in Y1 receptor expressing cells in the ipsilateral CA1 and CA3 sectors of the hippocampus, ipsi- and contralateral granule cell layer of the dentate gyrus and ipsilateral central nucleus of the amygdala was found, consistent with a reduction in Y1 receptor protein levels. The results suggest that plastic changes in hippocampal and/or amygdalar Y1 receptor expression may negatively impact anxiety levels. Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain and tight regulation and appropriate control of GABA is vital for neurochemical homeostasis. GABA transporter-1 (GAT-1) is abundantly expressed by neurones and astrocytes and plays a key role in GABA reuptake and regulation. Imbalance in GABA homeostasis has been implicated in epilepsy with GAT-1 being an attractive pharmacological target. Electron microscopy was used to examine the distribution, expression and morphology of GAT-1 expressing structures in the amygdala of the TLE model. Results suggest that GAT-1 was preferentially expressed on putative axon terminals over astrocytic processes in this TLE model. Myelin integrity was examined and results suggested that in the TLE model myelinated fibres were damaged in comparison to controls. Synaptic morphology was studied and results suggested that asymmetric (excitatory) synapses occurred more frequently than symmetric (inhibitory) synapses in the TLE model in comparison to controls. This study illustrated that the amygdala undergoes ultrastructural alterations in this TLE model. Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism, schizophrenia and also epilepsy. MIA was induced at a critical window of amygdalar development at E12 using bacterial mimetic lipopolysaccharide (LPS). Results showed that MIA activates cytokine, toll-like receptor and chemokine expression in the fetal brain that is prolonged in the postnatal amygdala. Inflammation elicited by MIA may prime the fetal brain for alterations seen in the glial environment and this in turn have deleterious effects on neuronal populations as seen in the amygdala at P14. These findings may suggest that MIA induced during amygdalar development may predispose offspring to amygdalar related disorders such as heightened anxiety, fear impairment and also neurodevelopmental disorders.

Growing up in a bubble: using germ-free animals to assess the influence of the gut microbiota on brain and behavior

There is a growing recognition of the importance of the commensal intestinal microbiota in the development and later function of the central nervous system. Research using germ-free mice (mice raised without any exposure to microorganisms) has provided some of the most persuasive evidence for a role of these bacteria in gut-brain signalling. Key findings show that the microbiota is necessary for normal stress responsivity, anxiety-like behaviors, sociability, and cognition. Furthermore, the microbiota maintains central nervous system homeostasis by regulating immune function and blood brain barrier integrity. Studies have also found that the gut microbiota influences neurotransmitter, synaptic, and neurotrophic signalling systems and neurogenesis. The principle advantage of the germ-free mouse model is in proof-of-principle studies and that a complete microbiota or defined consortiums of bacteria can be introduced at various developmental time points. However, a germ-free upbringing can induce permanent neurodevelopmental deficits that may deem the model unsuitable for specific scientific queries that do not involve early-life microbial deficiency. As such, alternatives and complementary strategies to the germ-free model are warranted and include antibiotic treatment to create microbiota-deficient animals at distinct time points across the lifespan. Increasing our understanding of the impact of the gut microbiota on brain and behavior has the potential to inform novel management strategies for stress-related gastrointestinal and neuropsychiatric disorders.

A study of the Zhiqing identity

More than seventeen million Chinese urban youth (Zhiqing in Chinese) went to the countryside, lived and engaged in agricultural work there during the Up to the Mountains and Down to the Countryside (UMDC) Movement (1967-1981). Although this movement was officially terminated in 1981, it has left an imprint on these people – the Zhiqing identity by which they are still characterized as a unique group in Chinese society and a special generation in Chinese history. Historical and sociological perspectives are combined in this study. By applying Glen H. Elder’s life course approach, the study reveals how Zhiqing’s life trajectories are embedded in the social history and identifies a series of interrelated factors that made Zhiqing into a unique generation. With the guidance of Henri Tajfel’s social identity theory, the study uncovers the emergence of the Zhiqing group and the Zhiqing identity, explains individuals’ acquisitions of the Zhiqing identity and analyzes how it has kept influencing individuals’ lives during and after the UMDC Movement. Using Zhiqing’s life stories allowed the researcher to combine the historical and sociological aspects in her examination of Zhiqing’s identity issues. In each life story, the narrator reviewed his/her life experience, reflected on socio-historical changes and expressed his/her emotions and ideas about identity issues. Utilizing methods of in-depth interview and thematic analysis, the researcher completed the study and presents this thesis as one interpretation on the Zhiqing identity, which, as according the researcher’s hermeneutic stance, is open to further discussion and future research.

The endless search for SA: spiritual ideology in Hindustāni music

This dissertation centres on philosophical attitudes presented by North Indian classical musicians in relation to the concept and experience of rāga improvisation. In Hindustāni music, there is a dynamic tension ideology and pragmatism, devotion and entertainment, fixity and improvisational freedom, and cognition and visceral experience. On one hand, rāga is an embodied methodological template for the creation of music. On the other hand, rāga improvisation is conceptualised as a path to metaphysical experience and as an evocation of an ineffable divine presence. A masterful rendition of rāga is both a re-enactment of a systematic prescribed formula and a spontaneous flow of consciousness. This study presents these apparent dichotomies to highlight ideological concerns, while simultaneously contextualising philosophical idealism in relation to pragmatic realities. A central paradigm is the manner in which pragmatic concerns are elevated in status and given spiritual significance. The dissertation begins with a view into historical and religious context. The discussion continues with a speculative investigation positing co-relations between Hindustāni music and central tenets of Indian philosophy, considering how rāga improvisation may manifest as a philosophy of sound. The study then explores the concept of rāga, a modal and conceptual construct that forms the heart of Indian classical music. The final three sections ground the subject of spiritual ideology within the life experience of Hindustāni musicians: ‘Transmission’ looks at the learning and enculturation process, which encapsulates values intrinsic to the ethos of Hindustāni music culture. ‘Practice’ explores the discipline, science and experience of musical practice, revealing core ideological concerns connecting spirituality to musical experience; and ‘Performance’ examines the live presentation of rāga improvisation, and the relationship between music as ‘entertainment’ and music as ‘devotion’. Both ethnographic and musicological, this research is the culmination of various fieldtrips to India, extensive interviews with Hindustāni musicians, fifteen year’s sitār training, and the study of relevant musicological and philosophical texts.

Geografia emocional d'un exode: La retirada republicana de 1939

This thesis proposes to trace and explore an emotional geography and cartography of the republican withdrawal at the end of the Spanish Civil War in Catalonia during the months of January and February 1939. Thus, it complements existing historiographical scholarship on the Spanish Civil War and Spanish Republican Exile, especially with regard to what was experienced in Catalan territory. However, its main purpose is not that of the historian, to reveal and explain unexplored stories, but to locate existing narratives, memoirs, journals and testimonies carefully in the landscape in which they took place, exposing their emotional bonds with the places and spaces of the withdrawal of the protagonists of the Republican exodus of 1939. Whilst there has been significant work in recent years to “recover” spaces associated with violent of traumatic memories of conflict and displacement, including the creation of a network of “Democratic Memory” places in Catalonia, the spaces explored in this thesis have not so far been construed as places of memory. In part, this is because of the diversity of emotions and affective responses they provoked and continue to evoke, but also because the geography of the Retirada is characterized by mobility and multiplicity. So instead of an historical approach, despite being influenced by Walter Benjamin's concept of history, this thesis draws on existing methods and approaches related to cultural geography, in particular, the emerging interdisciplinary field known as emotional geographies. In order to create a vision of La Retirada that is sensitive to its mobility and multiplicity, the primary methodology used has been that of interdisciplinary assemblage, juxtaposing images, documents and stories of past and present, in a process redolent of that which Marianne Hirsch calls "post-memory".