16,865 research outputs found

    A maternal high-fat diet during pregnancy and lactation induced depression-like behavior in offspring and myelin-related changes in the rat prefrontal cortex

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    In accordance with the developmental origins of health and disease, early-life environmental exposures, such as maternal diet, can enhance the probability and gravity of health concerns in their offspring in the future. Over the past few years, compelling evidence has emerged suggesting that prenatal exposure to a maternal high-fat diet (HFD) could trigger neuropsychiatric disorders in the offspring, such as depression. The majority of brain development takes place before birth and during lactation. Nevertheless, our understanding of the impact of HFD on myelination in the offspring’s brain during both gestation and lactation remains limited. In the present study, we investigated the effects of maternal HFD (60% energy from fat) on depressive-like and myelin-related changes in adolescent and adult rat offspring. Maternal HFD increased immobility time during the forced swimming test in both adolescent and adult offspring. Correspondingly, the depressive-like phenotype in offspring correlated with dysregulation of several genes and proteins in the prefrontal cortex, especially of myelin-oligodendrocyte glycoprotein (MOG), myelin and lymphocyte protein (MAL), 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNPase), kallikrein 6, and transferrin in male offspring, as well as of MOG and kallikrein 6 in female offspring, which persist even into adulthood. Maternal HFD also induced long-lasting adaptations manifested by the reduction of immature and mature oligodendrocytes in the prefrontal cortex in adult offspring. In summary, maternal HFD-induced changes in myelin-related genes are correlated with depressive-like behavior in adolescent offspring, which persists even to adulthood

    Non-Market Food Practices Do Things Markets Cannot: Why Vermonters Produce and Distribute Food That\u27s Not For Sale

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    Researchers tend to portray food self-provisioning in high-income societies as a coping mechanism for the poor or a hobby for the well-off. They describe food charity as a regrettable band-aid. Vegetable gardens and neighborly sharing are considered remnants of precapitalist tradition. These are non-market food practices: producing food that is not for sale and distributing food in ways other than selling it. Recent scholarship challenges those standard understandings by showing (i) that non-market food practices remain prevalent in high-income countries, (ii) that people in diverse social groups engage in these practices, and (iii) that they articulate diverse reasons for doing so. In this dissertation, I investigate the persistent pervasiveness of non-market food practices in Vermont. To go beyond explanations that rely on individual motivation, I examine the roles these practices play in society. First, I investigate the prevalence of non-market food practices. Several surveys with large, representative samples reveal that more than half of Vermont households grow, hunt, fish, or gather some of their own food. Respondents estimate that they acquire 14% of the food they consume through non-market means, on average. For reference, commercial local food makes up about the same portion of total consumption. Then, drawing on the words of 94 non-market food practitioners I interviewed, I demonstrate that these practices serve functions that markets cannot. Interviewees attested that non-market distribution is special because it feeds the hungry, strengthens relationships, builds resilience, puts edible-but-unsellable food to use, and aligns with a desired future in which food is not for sale. Hunters, fishers, foragers, scavengers, and homesteaders said that these activities contribute to their long-run food security as a skills-based safety net. Self-provisioning allows them to eat from the landscape despite disruptions to their ability to access market food such as job loss, supply chain problems, or a global pandemic. Additional evidence from vegetable growers suggests that non-market settings liberate production from financial discipline, making space for work that is meaningful, playful, educational, and therapeutic. Non-market food practices mend holes in the social fabric torn by the commodification of everyday life. Finally, I synthesize scholarly critiques of markets as institutions for organizing the production and distribution of food. Markets send food toward money rather than hunger. Producing for market compels farmers to prioritize financial viability over other values such as stewardship. Historically, people rarely if ever sell each other food until external authorities coerce them to do so through taxation, indebtedness, cutting off access to the means of subsistence, or extinguishing non-market institutions. Today, more humans than ever suffer from chronic undernourishment even as the scale of commercial agriculture pushes environmental pressures past critical thresholds of planetary sustainability. This research substantiates that alternatives to markets exist and have the potential to address their shortcomings

    UMSL Bulletin 2023-2024

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    The 2023-2024 Bulletin and Course Catalog for the University of Missouri St. Louis.https://irl.umsl.edu/bulletin/1088/thumbnail.jp

    Exploring the role of inflammation in major depressive disorder: beyond the monoamine hypothesis

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    Major depressive disorder affects approximately 8.4% of the United States population. The World Health Organization estimates that 280 million adults worldwide are suffering from depression. They have estimated that by 2030 it will be the second most serious condition. Current treatment relies on the monoamine hypothesis, however, one-third of patients with MDD do not respond to monoamine-based antidepressants. For years, it was hypothesized that the primary pathway of MDD involved serotonin as the main neurotransmitter. The monoamine hypothesis, a widely accepted theory, sought to explain the biological basis of MDD as being caused by the depletion of monoamine neurotransmitters, namely norepinephrine and serotonin. This hypothesis regarding monoamines as the pathophysiological basis of MDD led to the design and widespread use of selective serotonin reuptake inhibitors. However, given that only one-third of patients improve with SSRI it is reasonable to infer that the pathway involved is more complex than once hypothesized and there are more neurotransmitters, receptors, and molecules involved. The monoamine hypothesis does not explain why there is a delay in the onset of effect and action of SSRIs. Several studies have demonstrated that chronic stress is a risk factor for the development of MDD. Thus the monoamine hypothesis alone is not enough to fully account for the pathophysiology of MDD highlighting the need for further research involving the pathways of MDD. In this paper, we review the role of inflammation and cytokines on MDD and discuss other pathways involved in the development and persistence of depressive symptoms

    p-tau Ser356 is associated with Alzheimer's disease pathology and is lowered in brain slice cultures using the NUAK inhibitor WZ4003

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    Tau hyperphosphorylation and aggregation is a common feature of many dementia-causing neurodegenerative diseases. Tau can be phosphorylated at up to 85 different sites, and there is increasing interest in whether tau phosphorylation at specific epitopes, by specific kinases, plays an important role in disease progression. The AMP-activated protein kinase (AMPK)-related enzyme NUAK1 has been identified as a potential mediator of tau pathology, whereby NUAK1-mediated phosphorylation of tau at Ser356 prevents the degradation of tau by the proteasome, further exacerbating tau hyperphosphorylation and accumulation. This study provides a detailed characterisation of the association of p-tau Ser356 with progression of Alzheimer's disease pathology, identifying a Braak stage-dependent increase in p-tau Ser356 protein levels and an almost ubiquitous presence in neurofibrillary tangles. We also demonstrate, using sub-diffraction-limit resolution array tomography imaging, that p-tau Ser356 co-localises with synapses in AD postmortem brain tissue, increasing evidence that this form of tau may play important roles in AD progression. To assess the potential impacts of pharmacological NUAK inhibition in an ex vivo system that retains multiple cell types and brain-relevant neuronal architecture, we treated postnatal mouse organotypic brain slice cultures from wildtype or APP/PS1 littermates with the commercially available NUAK1/2 inhibitor WZ4003. Whilst there were no genotype-specific effects, we found that WZ4003 results in a culture-phase-dependent loss of total tau and p-tau Ser356, which corresponds with a reduction in neuronal and synaptic proteins. By contrast, application of WZ4003 to live human brain slice cultures results in a specific lowering of p-tau Ser356, alongside increased neuronal tubulin protein. This work identifies differential responses of postnatal mouse organotypic brain slice cultures and adult human brain slice cultures to NUAK1 inhibition that will be important to consider in future work developing tau-targeting therapeutics for human disease.</p

    Dementia with Lewy Bodies: Genomics, Transcriptomics, and Its Future with Data Science

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    Dementia with Lewy bodies (DLB) is a significant public health issue. It is the second most common neurodegenerative dementia and presents with severe neuropsychiatric symptoms. Genomic and transcriptomic analyses have provided some insight into disease pathology. Variants within SNCA, GBA, APOE, SNCB, and MAPT have been shown to be associated with DLB in repeated genomic studies. Transcriptomic analysis, conducted predominantly on candidate genes, has identified signatures of synuclein aggregation, protein degradation, amyloid deposition, neuroinflammation, mitochondrial dysfunction, and the upregulation of heat-shock proteins in DLB. Yet, the understanding of DLB molecular pathology is incomplete. This precipitates the current clinical position whereby there are no available disease-modifying treatments or blood-based diagnostic biomarkers. Data science methods have the potential to improve disease understanding, optimising therapeutic intervention and drug development, to reduce disease burden. Genomic prediction will facilitate the early identification of cases and the timely application of future disease-modifying treatments. Transcript-level analyses across the entire transcriptome and machine learning analysis of multi-omic data will uncover novel signatures that may provide clues to DLB pathology and improve drug development. This review will discuss the current genomic and transcriptomic understanding of DLB, highlight gaps in the literature, and describe data science methods that may advance the field

    Research trend of epigenetics and depression: adolescents' research needs to strengthen

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    ObjectiveWith its high prevalence, depression's pathogenesis remains unclear. Recent attention has turned to the interplay between depression and epigenetic modifications. However, quantitative bibliometric analyses are lacking. This study aims to visually analyze depression epigenetics trends, utilizing bibliometric tools, while comprehensively reviewing its epigenetic mechanisms.MethodsUtilizing the Web of Science core dataset, we collected depression and epigenetics-related studies. Employing VOSViewer software, we visualized data on authors, countries, journals, and keywords. A ranking table highlighted field leaders.ResultsAnalysis encompassed 3,469 depression epigenetics studies published from January 2002 to June 2023. Key findings include: (1) Gradual publication growth, peaking in 2021; (2) The United States and its research institutions leading contributions; (3) Need for enhanced collaborations, spanning international and interdisciplinary efforts; (4) Keyword clustering revealed five main themes—early-life stress, microRNA, genetics, DNA methylation, and histone acetylation—highlighting research hotspots; (5) Limited focus on adolescent depression epigenetics, warranting increased attention.ConclusionTaken together, this study revealed trends and hotspots in depression epigenetics research, underscoring global collaboration, interdisciplinary fusion, and multi-omics data's importance. It discussed in detail the potential of epigenetic mechanisms in depression diagnosis and treatment, advocating increased focus on adolescent research in this field. Insights aid researchers in shaping their investigative paths toward understanding depression's epigenetic mechanisms and antidepressant interventions

    Obesogenic Diets Cause Alterations on Proteins and Theirs Post-Translational Modifications in Mouse Brains

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    Obesity constitutes a major global health threat and is associated with a variety of diseases ranging from metabolic and cardiovascular disease, cancer to neurodegeneration. The hallmarks of neurodegeneration include oxidative stress, proteasome impairment, mitochondrial dysfunction and accumulation of abnormal protein aggregates as well as metabolic alterations. As an example, in post-mortem brain of patients with Alzheimer's disease (AD), several studies have reported reduction of insulin, insulin-like growth factor 1 and insulin receptor and an increase in tau protein and glycogen-synthase kinase-3 beta compared to healthy controls suggesting an impairment of metabolism in the AD patient's brain. Given these lines of evidence, in the present study we investigated brains of mice treated with 2 obesogenic diets, high-fat diet (HFD) and high-glycaemic diet (HGD), compared to mice fed with a standard diet (SD) employing a quantitative mass spectrometry-based approach. Moreover, post-translational modified proteins (phosphorylated and N-linked glycosylated) were studied. The aim of the study was to identify proteins present in the brain that are changing their expression based on the diet given to the mice. We believed that some of these changes would highlight pathways and molecular mechanisms that could link obesity to brain impairment. The results showed in this study suggest that, together with cytoskeletal proteins, mitochondria and metabolic proteins are changing their post-translational status in brains of obese mice. Specifically, proteins involved in metabolic pathways and in mitochondrial functions are mainly downregulated in mice fed with obesogenic diets compared to SD. These changes suggest a reduced metabolism and a lower activity of mitochondria in obese mice. Some of these proteins, such as PGM1 and MCT1 have been shown to be involved in brain impairment as well. These results might shed light on the well-studied correlation between obesity and brain damage. The results presented here are in agreement with previous findings and aim to open new perspectives on the connection between diet-induced obesity and brain impairment

    Neuroimmunopathology in Toxoplasmic Encephalitis

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    Toxoplasma gondii is a zoonotic protozoan parasite that causes mortality because of significant neuropathology. It is widespread in neonatal infections. Although the neuroimmunopathogenesis of toxoplasmic encephalitis (TE) has been studied for many years, it is still not completely understood, showing the disease’s severity. The urge to write this chapter comes at this stage. The sections covered in this chapter show the pathogenesis that has been established and characterized so far. The involvement of astrocytes and microglia in the development of neuropathology, which begins with tachyzoites crossing the blood-brain barrier during acute infection, has been explored. The molecular mechanism between schizophrenia and TE has been thoroughly proven. Uncovering the molecular pathogenesis of TE is critical for both understanding neuropathology and elucidating the link between neuropsychiatric diseases. Each part covered here is expected to contribute to developing novel therapeutic agents for the treatment and maybe prevention of neuropathology. The pathogenesis of the steady progression of encephalitis has been meticulously revealed. Thus, this chapter will offer significant insight into developing novel treatments for all organisms suffering from this disease

    The link between SARS-CoV-2 related microglial reactivity and astrocyte pathology in the inferior olivary nucleus

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    The pathological involvement of the central nervous system in SARS-CoV2 (COVID-19) patients is established. The burden of pathology is most pronounced in the brain stem including the medulla oblongata. Hypoxic/ischemic damage is the most frequent neuropathologic abnormality. Other neuropathologic features include neuronophagia, microglial nodules, and hallmarks of neurodegenerative diseases: astrogliosis and microglial reactivity. It is still unknown if these pathologies are secondary to hypoxia versus a combination of inflammatory response combined with hypoxia. It is also unknown how astrocytes react to neuroinflammation in COVID-19, especially considering evidence supporting the neurotoxicity of certain astrocytic phenotypes. This study aims to define the link between astrocytic and microglial pathology in COVID-19 victims in the inferior olivary nucleus, which is one of the most severely affected brain regions in COVID-19, and establish whether COVID-19 pathology is driven by hypoxic damage. Here, we conducted neuropathologic assessments and multiplex-immunofluorescence studies on the medulla oblongata of 18 COVID-19, 10 pre-pandemic patients who died of acute respiratory distress syndrome (ARDS), and 7–8 control patients with no ARDS or COVID-19. The comparison of ARDS and COVID-19 allows us to identify whether the pathology in COVID-19 can be explained by hypoxia alone, which is common to both conditions. Our results showed increased olivary astrogliosis in ARDS and COVID-19. However, microglial density and microglial reactivity were increased only in COVID-19, in a region-specific manner. Also, olivary hilar astrocytes increased YKL-40 (CHI3L1) in COVID-19, but to a lesser extent than ARDS astrocytes. COVID-19 astrocytes also showed lower levels of Aquaporin-4 (AQP4), and Metallothionein-3 in subsets of COVID-19 brain regions. Cluster analysis on immunohistochemical attributes of astrocytes and microglia identified ARDS and COVID-19 clusters with correlations to clinical history and disease course. Our results indicate that olivary glial pathology and neuroinflammation in the COVID-19 cannot be explained solely by hypoxia and suggest that failure of astrocytes to upregulate the anti-inflammatory YKL-40 may contribute to the neuroinflammation. Notwithstanding the limitations of retrospective studies in establishing causality, our experimental design cannot adequately control for factors external to our design. Perturbative studies are needed to confirm the role of the above-described astrocytic phenotypes in neuroinflammation
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