Anatomy and Neuroscience - Journal Articles

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Gut microbiome effects on neuronal excitability and activity: Implications for epilepsy
(Elsevier Inc., 2022-01-24) Darch, Henry; McCafferty, Cian P.; Horizon 2020; Science Foundation Ireland
It is now well established that the bacterial population of the gastrointestinal system, known as the gut microbiome, is capable of influencing the brain and its dependent functions. Links have been demonstrated between the microbiome and a variety of normal and pathological neural functions, including epilepsy. Many of these microbiome-brain links involve the direct or indirect modulation of the excitability and activity of individual neurons by the gut microbiome. Such links may be particularly significant when it comes to microbiome modulation of epilepsy, often considered a disorder of neuronal excitability. In this review we consider the current evidence of a relationship between the gut microbiome and the excitability or activity of neurons in the context of epilepsy. The review focuses particularly on evidence of direct, causal microbiome effects on neuronal excitability or activity, but also considers demonstrations of microbiome to host interactions that are likely to have an indirect influence. While we identify a few common themes, it is apparent that deriving general mechanistic principles of microbiome influence on these parameters in epilepsy will require considerable further study to tease out the many interacting factors, systems, and conditions.
Outrunning a bad diet: Interactions between exercise and a Western-style diet for adolescent mental health, metabolism and microbes
(Elsevier B.V., 2023-04-06) Nota, Minke H. C.; Nicolas, Sarah; O’Leary, Olivia F.; Nolan, Yvonne M.; Irish Research Council; Science Foundation Ireland
Adolescence is a period of biological, psychological and social changes, and the peak time for the emergence of mental health problems. During this life stage, brain plasticity including hippocampal neurogenesis is increased, which is crucial for cognitive functions and regulation of emotional responses. The hippocampus is especially susceptible to environmental and lifestyle influences, mediated by changes in physiological systems, resulting in enhanced brain plasticity but also an elevated risk for developing mental health problems. Indeed, adolescence is accompanied by increased activation of the maturing hypothalamic-pituitary-adrenal axis, sensitivity to metabolic changes due to increased nutritional needs and hormonal changes, and gut microbiota maturation. Importantly, dietary habits and levels of physical activity significantly impact these systems. In this review, the interactions between exercise and Western-style diets, which are high in fat and sugar, on adolescent stress susceptibility, metabolism and the gut microbiota are explored. We provide an overview of current knowledge on implications of these interactions for hippocampal function and adolescent mental health, and speculate on potential mechanisms which require further investigation.
Age-associated deficits in social behaviour are microbiota-dependent
(Elsevier, 2023) Cruz-Pereira, Joana S.; Moloney, Gerard M.; Bastiaanssen, Thomaz F. S.; Boscaini, Serena; Fitzgerald, Patrick; Clarke, Gerard; Cryan, John F.; Science Foundation Ireland; Saks-Kavanaugh Foundation; Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Aging is associated with remodelling of immune and central nervous system responses resulting in behavioural impairments including social deficits. Growing evidence suggests that the gut microbiome is also impacted by aging, and we propose that strategies to reshape the aged gut microbiome may ameliorate some age-related effects on host physiology. Thus, we assessed the impact of gut microbiota depletion, using an antibiotic cocktail, on aging and its impact on social behavior and the immune system. Indeed, microbiota depletion in aged mice eliminated the age-dependent deficits in social recognition. We further demonstrate that although age and gut microbiota depletion differently shape the peripheral immune response, aging induces an accumulation of T cells in the choroid plexus, that is partially blunted following microbiota depletion. Moreover, an untargeted metabolomic analysis revealed age-dependent alterations of cecal metabolites that are reshaped by gut microbiota depletion. Together, our results suggest that the aged gut microbiota can be specifically targeted to affect social deficits. These studies propel the need for future investigations of other non-antibiotic microbiota targeted interventions on age-related social deficits both in animal models and humans.
Stress during puberty exerts sex-specific effects on depressive-like behavior and monoamine neurotransmitters in adolescence and adulthood
(Elsevier Inc., 2022-10-07) Harris, Erin P.; Villalobos-Manriquez, Francisca; Melo, Thieza G.; Clarke, Gerard; O'Leary, Olivia F.; Health Research Board; Science Foundation Ireland
Psychiatric disorders including major depression are twice as prevalent in women compared to men. This sex difference in prevalence only emerges after the onset of puberty, suggesting that puberty may be a sensitive period during which sex-associated vulnerability to stress-related depression might become established. Thus, this study investigated whether stress occurring specifically during the pubertal window of adolescence may be responsible for this sex difference in depression vulnerability. Male and female rats were exposed to a three-day stress protocol during puberty (postnatal days 35–37 in females, 45–47 in males) and underwent behavioral tests in adolescence or adulthood measuring anhedonia, anxiety-like behavior, locomotor activity and antidepressant-like behavior. Brainstem and striatum tissue were collected from a separate cohort of behavioral test-naïve rats in adolescence or adulthood to quantify the effect of pubertal stress on monoamine neurotransmitters. Pubertal stress increased immobility behavior in the forced swim test in both sexes in adolescence and adulthood. In adolescence, pubertal stress altered escape-oriented behaviors in a sex-specific manner: decreasing climbing in males but not females and decreasing swimming in females but not males. Pubertal stress decreased adolescent brainstem noradrenaline specifically in females and had opposing effects in adolescent males and females on brainstem serotonin turnover. Pubertal stress induced anhedonia in the saccharin preference test in adult males but not females, an effect paralleled by a male-specific decrease in striatal dopamine turnover. Pubertal stress did not significantly impact anxiety-like behavior or locomotor activity in any sex at either age. Taken together, these data suggest that although pubertal stress did not preferentially increase female vulnerability to depressive-like behaviors compared to males, stress during puberty exerts sex-specific effects on depressive-like behavior and anhedonia, possibly through discrete neurotransmitter systems.
Heterogeneity of lithium effects in the forced swim test, across more than within experiments
(Cambridge University Press, 2022-05-30) Kazavchinsky, Lydmila; Kara, Nirit Z.; Einat, Haim

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