Anatomy and Neuroscience - Journal Articles
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Item More than just a number: the gut microbiota and brain function across the extremes of life(Taylor & Francis, 2024) Nuzum, Nathan D.; Deady, Clara; Kittel-Schneider, Sarah; Cryan, John F.; O'Mahony, Siobhain M.; Clarke, Gerard; Science Foundation IrelandUnderstanding the interrelationship between the gut microbiota and host physiology, although still in its relative infancy, has taken important steps forward over the past decade. In the context of brain disorders including those characterized by neurodevelopmental and neurodegenerative changes there have been important advances. However, initially research involved correlational analyses, had limited translational scope, and lacked functional assessments. Thus, largescale longitudinal clinical investigations that assess causation and underlying mechanisms via in depth analysis methods are needed. In neurodegeneration research, strong causal evidence now links the gut microbiome to Alzheimer's (AD), and Parkinson's Disease (PD), as supported by human-to-animal transplantation studies. Longitudinal interventions are being conducted in AD, PD, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. Neurodevelopmental research has also seen a boon in microbiome-related clinical research including in autism, Attention-deficit/hyperactivity disorder, and schizophrenia, which is confirming prior animal model work regarding the key time-windows in the gut microbiome important for infant cognition. While recent research advances represent important progress, fundamental knowledge gaps and obstacles remain. Knowing how and why the gut microbiome changes at the extremes of life will develop our mechanistic understanding and help build the evidence base as we strive toward counteracting microbial missteps with precision therapeutic interventions.Item Differential cortical aspartate uptake across the oestrous cycle is associated with changes in gut microbiota in Wistar-Kyoto rats(Elsevier B.V., 2024-12-26) Sajjad, Jahangir; Morael, Jennifer; Melo, Thieza G.; Foley, Tara; Murphy, Amy; Keane, James; Popov, Jelena; Stanton, Catherine; Dinan, Timothy G.; Clarke, Gerard; Cryan, John F.; Collins, James M.; O’Mahony, Siobhain M.; Science Foundation IrelandPain and psychological stress are intricately linked, with sex differences evident in disorders associated with both systems. Glutamatergic signalling in the central nervous system is influenced by gonadal hormones via the hypothalamic–pituitary–adrenal axis and is central in pain research. Emerging evidence supports an important role for the gut microbiota in influencing pain signalling. Here, the functional activity of excitatory amino acid transporters (EAATs) in the anterior cingulate cortex (ACC) and lumbosacral spinal cord of male and female Wistar-Kyoto rats, an animal model of comorbid visceral hypersensitivity and enhanced stress responsivity, was investigated across the oestrous cycle. Correlations between the gut microbiota and changes in the functional activity of the central glutamatergic system were also investigated. EAAT function in the lumbosacral spinal cord was similar between males and females across the oestrous cycle. EAAT function was higher in the ACC of dioestrus females compared to proestrus and oestrus females. In males, aspartate uptake in the ACC positively correlated with Bacteroides, while aspartate uptake in the spinal cord positively correlated with the relative abundance of Lachnospiraceae NK4A136. Positive associations with aspartate uptake in the spinal cord were also observed for Alistipes and Bifidobacterium during oestrus, and Eubacterium coprostanoligenes during proestrus. Clostridium sensu stricto1 was negatively associated with aspartate uptake in the ACC in males and dioestrus females. These data indicate that glutamate metabolism in the ACC is oestrous stage-dependent and that short-chain fatty acid-producing bacteria are positively correlated with aspartate uptake in males and during specific oestrous stages in females.Item Symposium: What does the microbiome tell us about prevention and treatment of AD/ADRD?(Society for Neuroscience, 2024-10-09) Capocchi, Joia K.; Figueroa-Romero, Claudia; Dunham, Sage J. B.; Faraci, Gina; Rothman, Jason A.; Whiteson, Katrine L.; Seo, Dong-oh; Holtzman, David M.; Grabrucker, Stefanie; Nolan, Yvonne M.; Kaddurah-Daouk, Rima; Jett, David A.; Good Ventures Foundation; Cure Alzheimer’s Fund; Science Foundation Ireland; National Institute on Aging; Foundation for the National Institutes of HealthAlzheimer's disease (AD) and Alzheimer's disease-related dementias (ADRDs) are broad-impact multifactorial neurodegenerative diseases. Their complexity presents unique challenges for developing effective therapies. This review highlights research presented at the 2024 Society for Neuroscience meeting which emphasized the gut microbiome's role in AD pathogenesis by influencing brain function and neurodegeneration through the microbiota–gut–brain axis. This emerging evidence underscores the potential for targeting the gut microbiota to treat AD/ADRD.Item Gut microbiota and eating behaviour in circadian syndrome(Elsevier Ltd., 2024-08-01) Soliz-Rueda, Jorge R.; Cuesta-Marti, Cristina; O’Mahony, Siobhain M.; Clarke, Gerard; Schellekens, Harriët; Muguerza, Begoña; Science Foundation Ireland; Ministerio de Ciencia e Innovación; Irish Research Council; Ministerio de Universidades; Biostime Institute for Nutrition and Care – Geneva; Food for Health IrelandEating behaviour and circadian rhythms are closely related. The type, timing, and quantity of food consumed, and host circadian rhythms, directly influence the intestinal microbiota, which in turn impacts host circadian rhythms and regulates food intake beyond homeostatic eating. This Opinion discusses the impact of food intake and circadian disruptions induced by an obesogenic environment on gut–brain axis signalling. We also explore potential mechanisms underlying the effects of altered gut microbiota on food intake behaviour and circadian rhythmicity. Understanding the crosstalk between gut microbiota, circadian rhythms, and unhealthy eating behaviour is crucial to addressing the obesity epidemic, which remains one of the biggest societal challenges of our time.Item A closer look at the subordinate population within the visible burrow system(Elsevier Inc., 2017-07-13) Melhorn, Susan J.; Elfers, Clinton T.; Scott, Karen A.; Sakai, Randall R.The visible burrow system (VBS) utilizes the natural social behavior of rodents to model chronic social stress. Classically, when male and female rats are housed together in the VBS a dominance hierarchy rapidly forms with one dominant (DOM) and three subordinate (SUB) males. SUB animals show signs of chronic social stress, including loss of body weight and elevated basal corticosterone. This study furthered examined differences among the SUB population. Quantitative observations across numerous VBS colonies within the Sakai Lab suggest that there is variability in the effects of stress on the SUB population, specifically that some animals may experience more severe effects of chronic social stress than others. To further examine this observation, SUB animals were classified as OMEGA if they received a disproportionate amount of their colonies' wounds. OMEGA animals received more wounds to their body compared to SUB (P < 0.0001) and lost significantly more weight throughout the stress period compared to all other VBS-housed animals (group × time interaction P < 0.0001). Following VBS housing it was determined the OMGEA also lost lean body mass (P < 0.01 vs. controls and DOM), are hyporesponsive to an acute restraint challenge (P < 0.01 vs all other groups) and show depressive-like behavior during a forced swim test. Furthermore, expression of neuropeptide Y within the amygdala, known for anxiolytic properties following chronic stress, was elevated among OMEGA (group × region interaction P < 0.001). Together these observations suggest that an additional phenotype exists among the SUB animals within a VBS colony and represents the variability of the effects of chronic social stress.