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Metabolites Dec 2022Ischemic stroke is one of the leading global causes of neurological morbidity and decease. Its etiology depends on multiple events such as cardiac embolism, brain... (Review)
Review
Ischemic stroke is one of the leading global causes of neurological morbidity and decease. Its etiology depends on multiple events such as cardiac embolism, brain capillaries occlusion and atherosclerosis, which ultimately culminate in blood flow interruption, incurring hypoxia and nutrient deprivation. Thyroid hormones (THs) are pleiotropic modulators of several metabolic pathways, and critically influence different aspects of tissues development. The brain is a key TH target tissue and both hypo- and hyperthyroidism, during embryonic and adult life, are associated with deranged neuronal formation and cognitive functions. Accordingly, increasing pieces of evidence are drawing attention on the consistent relationship between the THs status and the acute cerebral and cardiac diseases. However, the concrete contribution of THs systemic or local alteration to the pathology outcome still needs to be fully addressed. In this review, we aim to summarize the multiple influences that THs exert on the brain and heart patho-physiology, to deepen the reasons for the harmful effects of hypo- and hyperthyroidism on these organs and to provide insights on the intricate relationship between the THs variations and the pathological alterations that take place after the ischemic injury.
PubMed: 36676947
DOI: 10.3390/metabo13010022 -
Neurobiology of Stress Mar 2022Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully... (Review)
Review
Psychological trauma is highly prevalent among psychiatric disorders, however, the relationship between trauma, neurobiology and psychopathology is not yet fully understood. The cerebellum has been recognized as a crucial structure for cognition and emotion, however, it has been relatively ignored in the literature of psychological trauma, as it is not considered as part of the traditional fear neuro-circuitry. The aim of this review is to investigate how psychological trauma affects the cerebellum and to make conclusive remarks on whether the cerebellum forms part of the trauma-affected brain circuitry. A total of 267 unique records were screened and 39 studies were included in the review. Structural cerebellar alterations and aberrant cerebellar activity and connectivity in trauma-exposed individuals were consistently reported across studies. Early-onset of adverse experiences was associated with cerebellar alterations in trauma-exposed individuals. Several studies reported alterations in connectivity between the cerebellum and nodes of large-brain networks, which are implicated in several psychiatric disorders, including the default mode network, the salience network and the central executive network. Also, trauma-exposed individuals showed altered resting state and task based cerebellar connectivity with cortical and subcortical structures that are involved in emotion and fear regulation. Our preferred interpretation of the results is through the lens of the Universal Cerebellar Transform, the hypothesis that the cerebellum, given its homogeneous cytoarchitecture, performs a common computation for motor, cognitive and emotional functions. Therefore, trauma-induced alterations in this computation might set the ground for a variety of psychiatric symptoms.
PubMed: 35146077
DOI: 10.1016/j.ynstr.2022.100429 -
ELife Oct 2020Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly...
Psychedelic drugs are potent modulators of conscious states and therefore powerful tools for investigating their neurobiology. N,N, Dimethyltryptamine (DMT) can rapidly induce an extremely immersive state of consciousness characterized by vivid and elaborate visual imagery. Here, we investigated the electrophysiological correlates of the DMT-induced altered state from a pool of participants receiving DMT and (separately) placebo (saline) while instructed to keep their eyes closed. Consistent with our hypotheses, results revealed a spatio-temporal pattern of cortical activation (i.e. travelling waves) similar to that elicited by visual stimulation. Moreover, the typical top-down alpha-band rhythms of closed-eyes rest were significantly decreased, while the bottom-up forward wave was significantly increased. These results support a recent model proposing that psychedelics reduce the 'precision-weighting of priors', thus altering the balance of top-down versus bottom-up information passing. The robust hypothesis-confirming nature of these findings imply the discovery of an important mechanistic principle underpinning psychedelic-induced altered states.
Topics: Adult; Alpha Rhythm; Brain; Consciousness; Female; Hallucinogens; Humans; Male; Middle Aged; N,N-Dimethyltryptamine; Young Adult
PubMed: 33043883
DOI: 10.7554/eLife.59784 -
Proceedings of the National Academy of... Oct 2022In the United States, systemic racism has had lasting effects on the structure of cities, specifically due to government-mandated redlining policies that produced...
In the United States, systemic racism has had lasting effects on the structure of cities, specifically due to government-mandated redlining policies that produced racially segregated neighborhoods that persist today. However, it is not known whether varying habitat structures and natural resource availability associated with racial segregation affect the demographics and evolution of urban wildlife populations. To address this question, we repurposed and reanalyzed publicly archived nuclear genetic data from 7,698 individuals spanning 39 terrestrial vertebrate species sampled in 268 urban locations throughout the United States. We found generally consistent patterns of reduced genetic diversity and decreased connectivity in neighborhoods with fewer White residents, likely because of environmental differences across these neighborhoods. The strength of relationships between the racial composition of neighborhoods, genetic diversity, and differentiation tended to be weak relative to other factors affecting genetic diversity, possibly in part due to the recency of environmental pressures on urban wildlife populations. However, the consistency of the direction of effects across disparate taxa suggest that systemic racism alters the demography of urban wildlife populations in ways that generally limit population sizes and negatively affect their chances of persistence. Our results thus support the idea that limited capacity to support large, well-connected wildlife populations reduces access to nature and builds on existing environmental inequities shouldered by predominantly non-White neighborhoods.
Topics: Humans; Animals; United States; Animals, Wild; Systemic Racism; Ecosystem; Urban Population; Residence Characteristics; Genetic Variation; Racism
PubMed: 36256811
DOI: 10.1073/pnas.2102860119 -
Frontiers in Synaptic Neuroscience 2023The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological... (Review)
Review
The synapse has consistently been considered a vulnerable and critical target within Alzheimer's disease, and synapse loss is, to date, one of the main biological correlates of cognitive decline within Alzheimer's disease. This occurs prior to neuronal loss with ample evidence that synaptic dysfunction precedes this, in support of the idea that synaptic failure is a crucial stage within disease pathogenesis. The two main pathological hallmarks of Alzheimer's disease, abnormal aggregates of amyloid or tau proteins, have had demonstrable effects on synaptic physiology in animal and cellular models of Alzheimer's disease. There is also growing evidence that these two proteins may have a synergistic effect on neurophysiological dysfunction. Here, we review some of the main findings of synaptic alterations in Alzheimer's disease, and what we know from Alzheimer's disease animal and cellular models. First, we briefly summarize some of the human evidence to suggest that synapses are altered, including how this relates to network activity. Subsequently, animal and cellular models of Alzheimer's disease are considered, highlighting mouse models of amyloid and tau pathology and the role these proteins may play in synaptic dysfunction, either in isolation or examining how the two pathologies may interact in dysfunction. This specifically focuses on neurophysiological function and dysfunction observed within these animal models, typically measured using electrophysiology or calcium imaging. Following synaptic dysfunction and loss, it would be impossible to imagine that this would not alter oscillatory activity within the brain. Therefore, this review also discusses how this may underpin some of the aberrant oscillatory patterns seen in animal models of Alzheimer's disease and human patients. Finally, an overview of some key directions and considerations in the field of synaptic dysfunction in Alzheimer's disease is covered. This includes current therapeutics that are targeted specifically at synaptic dysfunction, but also methods that modulate activity to rescue aberrant oscillatory patterns. Other important future avenues of note in this field include the role of non-neuronal cell types such as astrocytes and microglia, and mechanisms of dysfunction independent of amyloid and tau in Alzheimer's disease. The synapse will certainly continue to be an important target within Alzheimer's disease for the foreseeable future.
PubMed: 36970154
DOI: 10.3389/fnsyn.2023.1129036 -
Scientific Reports Apr 2023In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of...
In contrast to long-term relationships, far less is known about the temporal evolution of transient relationships, although these constitute a substantial fraction of people's communication networks. Previous literature suggests that ratings of relationship emotional intensity decay gradually until the relationship ends. Using mobile phone data from three countries (US, UK, and Italy), we demonstrate that the volume of communication between ego and its transient alters does not display such a systematic decay, instead showing a lack of any dominant trends. This means that the communication volume of egos to groups of similar transient alters is stable. We show that alters with longer lifetimes in ego's network receive more calls, with the lifetime of the relationship being predictable from call volume within the first few weeks of first contact. This is observed across all three countries, which include samples of egos at different life stages. The relation between early call volume and lifetime is consistent with the suggestion that individuals initially engage with a new alter so as to evaluate their potential as a tie in terms of homophily.
Topics: Humans; Social Support; Emotions; Ego; Cell Phone; Italy
PubMed: 37059731
DOI: 10.1038/s41598-023-32206-2 -
Frontiers in Immunology 2023Vancomycin is a broad-spectrum antibiotic widely used in cases of suspected sepsis in premature neonates. While appropriate and potentially lifesaving in this setting,...
Vancomycin is a broad-spectrum antibiotic widely used in cases of suspected sepsis in premature neonates. While appropriate and potentially lifesaving in this setting, early-life antibiotic exposure alters the developing microbiome and is associated with an increased risk of deadly complications, including late-onset sepsis (LOS) and necrotizing enterocolitis (NEC). Recent studies show that neonatal vancomycin treatment disrupts postnatal enteric nervous system (ENS) development in mouse pups, which is in part dependent upon neuroimmune interactions. This suggests that early-life antibiotic exposure could disrupt these interactions in the neonatal gut. Notably, a subset of tissue-resident intestinal macrophages, muscularis macrophages, has been identified as important contributors to the development of postnatal ENS. We hypothesized that vancomycin-induced neonatal dysbiosis impacts postnatal ENS development through its effects on macrophages. Using a mouse model, we found that exposure to vancomycin in the first 10 days of life, but not in adult mice, resulted in an expansion of pro-inflammatory colonic macrophages by increasing the recruitment of bone-marrow-derived macrophages. Single-cell RNA sequencing of neonatal colonic macrophages revealed that early-life vancomycin exposure was associated with an increase in immature and inflammatory macrophages, consistent with an influx of circulating monocytes differentiating into macrophages. Lineage tracing confirmed that vancomycin significantly increased the non-yolk-sac-derived macrophage population. Consistent with these results, early-life vancomycin exposure did not expand the colonic macrophage population nor decrease enteric neuron density in CCR2-deficient mice. Collectively, these findings demonstrate that early-life vancomycin exposure alters macrophage number and phenotypes in distinct ways compared with vancomycin exposure in adult mice and results in altered ENS development.
Topics: Mice; Animals; Vancomycin; Dysbiosis; Gastrointestinal Microbiome; Macrophages; Anti-Bacterial Agents; Neurons; Sepsis
PubMed: 37901245
DOI: 10.3389/fimmu.2023.1268909 -
International Journal of Molecular... Mar 2023Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm characterized by bone marrow dysplasia, failure of hematopoiesis and variable risk of progression to... (Review)
Review
Myelodysplastic syndrome (MDS) is a clonal hematopoietic neoplasm characterized by bone marrow dysplasia, failure of hematopoiesis and variable risk of progression to acute myeloid leukemia (AML). Recent large-scale studies have demonstrated that distinct molecular abnormalities detected at earlier stages of MDS alter disease biology and predict progression to AML. Consistently, various studies analyzing these diseases at the single-cell level have identified specific patterns of progression strongly associated with genomic alterations. These pre-clinical results have solidified the conclusion that high-risk MDS and AML arising from MDS or AML with MDS-related changes (AML-MRC) represent a continuum of the same disease. AML-MRC is distinguished from de novo AML by the presence of certain chromosomal abnormalities, such as deletion of 5q, 7/7q, 20q and complex karyotype and somatic mutations, which are also present in MDS and carry crucial prognostic implications. Recent changes in the classification and prognostication of MDS and AML by the International Consensus Classification (ICC) and the World Health Organization (WHO) reflect these advances. Finally, a better understanding of the biology of high-risk MDS and the mechanisms of disease progression have led to the introduction of novel therapeutic approaches, such as the addition of venetoclax to hypomethylating agents and, more recently, triplet therapies and agents targeting specific mutations, including FLT3 and IDH1/2. In this review, we analyze the pre-clinical data supporting that high-risk MDS and AML-MRC share the same genetic abnormalities and represent a continuum, describe the recent changes in the classification of these neoplasms and summarize the advances in the management of patients with these neoplasms.
Topics: Humans; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Chromosome Aberrations; Mutation
PubMed: 36902450
DOI: 10.3390/ijms24055018 -
Psychological Medicine Nov 2023Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these...
BACKGROUND
Depression is associated with metabolic alterations including lipid dysregulation, whereby associations may vary across individual symptoms. Evaluating these associations using a network perspective yields a more complete insight than single outcome-single predictor models.
METHODS
We used data from the Netherlands Study of Depression and Anxiety ( = 2498) and leveraged networks capturing associations between 30 depressive symptoms (Inventory of Depressive Symptomatology) and 46 metabolites. Analyses involved 4 steps: creating a network with Mixed Graphical Models; calculating centrality measures; bootstrapping for stability testing; validating central, stable associations by extra covariate-adjustment; and validation using another data wave collected 6 years later.
RESULTS
The network yielded 28 symptom-metabolite associations. There were 15 highly-central variables (8 symptoms, 7 metabolites), and 3 stable links involving the symptoms Low energy (fatigue), and Hypersomnia. Specifically, fatigue showed consistent associations with higher mean diameter for VLDL particles and lower estimated degree of (fatty acid) unsaturation. These remained present after adjustment for lifestyle and health-related factors and using another data wave.
CONCLUSIONS
The somatic symptoms Fatigue and Hypersomnia and cholesterol and fatty acid measures showed central, stable, and consistent relationships in our network. The present analyses showed how metabolic alterations are more consistently linked to specific symptom profiles.
Topics: Humans; Depression; Anxiety; Fatigue; Disorders of Excessive Somnolence; Fatty Acids
PubMed: 37092859
DOI: 10.1017/S0033291723001009 -
Cognitive Research: Principles and... Nov 2022Face masks became prevalent across the globe as an efficient tool to stop the spread of COVID-19. A host of studies already demonstrated that masks lead to changes in...
Face masks became prevalent across the globe as an efficient tool to stop the spread of COVID-19. A host of studies already demonstrated that masks lead to changes in facial identification and emotional expression processing. These changes were documented across ages and were consistent even with the increased exposure to masked faces. Notably, mask-wearing also changes the state of the observers in regard to their own bodies and other agents. Previous research has already demonstrated a plausible association between observers' states and their perceptual behaviors. Thus, an outstanding question is whether mask-wearing would alter face recognition abilities. To address this question, we conducted a set of experiments in which participants were asked to recognize non-masked faces (Experiment 1), masked faces (Experiment 2) and novel objects (Experiment 3) while they were either masked or unmasked. Mask wearing hindered face perception abilities but did not modulate object recognition ability. Finally, we demonstrated that the decrement in face perception ability relied on wearing the mask on distinctive facial features (Experiment 4). Together, these findings reveal a novel effect of mask-wearing on face recognition. We discuss these results considering the plausible effect of somatosensory stimulation on visual processing as well as the effect of involuntary perspective taking.
Topics: Humans; Facial Recognition; COVID-19; Masks; Visual Perception
PubMed: 36380225
DOI: 10.1186/s41235-022-00444-z