Anatomy and Neuroscience - Journal Articles

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    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.
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    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.
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    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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    Lipidome analysis in brain and peripheral plasma following milk fat globule membrane supplementation in rodents
    (Wiley, 2022-09-06) Davies, R.; van Diepen, J. A.; Brink, L. R.; Bijlsma, S.; Neufeld, K. M.; Cryan, John F.; O'Mahony, Siobhain M.; Bobeldijk, I.; Gross, G.; Mead Johnson Nutrition; Reckitt Benckiser Pharmaceuticals
    Scope: Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigated bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induced parallel changes to plasma and brain lipidomes. Methods and results: Transgenic APOE*3.Leiden mice (n = 18/group) and Sprague-Dawley rats (n = 12/group) were fed bMFGM-enriched (MFGM+) or Control diet, after which phospholipid profiles were determined in peripheral plasma, hippocampus and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrated a clear separation between MFGM+ and Control plasma samples across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) were significantly and consistently higher in the circulation of MFGM+ versus Control groups. A similar trend was observed in rat prefrontal cortex, although no significant separation of the brain lipidome was demonstrated. Conclusion: bMFGM-enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with some similar, but non-significant, trends in central regions of the brain. These changes may contribute to the beneficial effects of dietary bMFGM on neurodevelopment during early life.
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    A framework for AI-assisted detection of Patent Ductus Arteriosus from neonatal phonocardiogram
    (MDPI, 2021-02-05) Gómez-Quintana, Sergi; Schwarz, Christoph E.; Shelevytsky, Ihor; Shelevytska, Victoriya; Semenova, Oksana; Factor, Andreea; Popovici, Emanuel; Temko, Andriy; Science Foundation Ireland; Deutsche Forschungsgemeinschaft; Wellcome Trust; Grand Challenges Canada
    The current diagnosis of Congenital Heart Disease (CHD) in neonates relies on echocardiography. Its limited availability requires alternative screening procedures to prioritise newborns awaiting ultrasound. The routine screening for CHD is performed using a multidimensional clinical examination including (but not limited to) auscultation and pulse oximetry. While auscultation might be subjective with some heart abnormalities not always audible it increases the ability to detect heart defects. This work aims at developing an objective clinical decision support tool based on machine learning (ML) to facilitate differentiation of sounds with signatures of Patent Ductus Arteriosus (PDA)/CHDs, in clinical settings. The heart sounds are pre-processed and segmented, followed by feature extraction. The features are fed into a boosted decision tree classifier to estimate the probability of PDA or CHDs. Several mechanisms to combine information from different auscultation points, as well as consecutive sound cycles, are presented. The system is evaluated on a large clinical dataset of heart sounds from 265 term and late-preterm newborns recorded within the first six days of life. The developed system reaches an area under the curve (AUC) of 78% at detecting CHD and 77% at detecting PDA. The obtained results for PDA detection compare favourably with the level of accuracy achieved by an experienced neonatologist when assessed on the same cohort.