The impact of manganese on vascular endothelium.

Manganese (Mn) is an essential trace element involved in various physiological processes, but excessive exposure may lead to toxicity. The vascular endothelium, a monolayer of endothelial cells within blood vessels, is a primary target of Mn toxicity. This review provides a comprehensive overview of the impact of Mn on vascular endothelium, focusing on both peripheral and brain endothelial cells.

JAK2/STAT3 signaling pathway mediates methylmercury toxicity in mouse astrocyte neuronal C8-D1A cell line.

Methylmercury (MeHg) is an environmental pollutant. Consumption of contaminated fish is the main exposure route in humans, leading to severe neurological disorders. Upon ingestion MeHg reaches the brain and selectively accumulates in astrocytes disrupting glutamate and calcium homeostasis and increasing oxidative stress.

Association between Heavy Metals, Metalloids and Metabolic Syndrome: New Insights and Approaches.

Metabolic syndrome (MetS) is an important public health issue that affects millions of people around the world and is growing to pandemic-like proportions. This syndrome is defined by the World Health Organization (WHO) as a pathologic condition characterized by abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. Moreover, the etiology of MetS is multifactorial, involving many environmental factors, including toxicant exposures.

Amyloid Beta Peptide-Mediated Alterations in Mitochondrial Dynamics and its Implications for Alzheimer's Disease.

Alzheimer's disease (AD) is considered the most frequent neurodegenerative disorder worldwide, compromising cognitive function in patients, with an average incidence of 1-3% in the open population. Protein aggregation into amyloidogenic plaques and neurofibrillary tangles, as well as neurodegeneration in the hippocampal and cortical areas, represent the neuropathological hallmarks of this disorder. Mechanisms involved in neurodegeneration include protein misfolding, augmented apoptosis, disrupted molecular signaling pathways and axonal transport, oxidative stress, inflammation, and mitochondrial dysfunction, among others.

Alpha-Mangostin Alleviates the Short-term 6-Hydroxydopamine-Induced Neurotoxicity and Oxidative Damage in Rat Cortical Slices and in Caenorhabditis elegans.

The development, at the experimental level, of therapeutic strategies based on natural products to attenuate neurological alterations in degenerative disorders has gained attention. Antioxidant molecules exhibit both anti-inflammatory and neuroprotective properties. Alpha-mangostin (α-Man) is a natural xanthonoid isolated from the mangosteen tree with demonstrated antioxidant and cytoprotective properties.

Ghrelin attenuates methylmercury-induced oxidative stress in neuronal cells.

Methylmercury (MeHg) is a global pollutant, which can cause damage to the central nervous system at both high-acute and chronic-low exposures, especially in vulnerable populations, such as children and pregnant women. Nowadays, acute-high poisoning is rare. However, chronic exposure to low MeHg concentrations via fish consumption remains a health concern.

BXD Recombinant Inbred Mice as a Model to Study Neurotoxicity.

BXD recombinant inbred (RI) lines represent a genetic reference population derived from a cross between C57BL/6J mice (B6) and DBA/2J mice (D2), which through meiotic recombination events possesses recombinant chromosomes containing B6 or D2 haplotype segments. The quantitative trait loci (QTLs) are the locations of segregating genetic polymorphisms and are fundamental to understanding genetic diversity in human disease susceptibility and severity. QTL mapping represents the typical approach for identifying naturally occurring polymorphisms that influence complex phenotypes.

The antioxidant role of STAT3 in methylmercury-induced toxicity in mouse hypothalamic neuronal GT1-7 cell line.

Oxidative stress, impairment of antioxidant defenses, and disruption of calcium homeostasis are associated with the toxicity of methylmercury (MeHg). Yet, the relative contribution and interdependence of these effects and other molecular mechanisms that mediate MeHg-induced neurotoxicity remain uncertain. The signal transducer and activator of transcription 3 (STAT3) is a transcription factor that regulates the expression of anti-apoptotic and cell cycle progression genes.

Adipotropic effects of heavy metals and their potential role in obesity.

Epidemiological studies demonstrated an association between heavy metal exposure and the incidence of obesity and metabolic syndrome. However, the particular effects of metal toxicity on adipose tissue functioning are unclear. Therefore, recent findings of direct influence of heavy metals (mercury, cadmium, and lead) and metalloid (arsenic) on adipose tissue physiology are discussed while considering existing gaps and contradictions.

Chronic exposure to methylmercury enhances the anorexigenic effects of leptin in C57BL/6J male mice.

Several studies have demonstrated that heavy metals disrupt energy homeostasis. Leptin inhibits food intake and decreases body weight through activation of its receptor in the hypothalamus. The impact of heavy metals on leptin signaling in the hypothalamus is unclear.

Chronic exposure to methylmercury disrupts ghrelin actions in C57BL/6J mice.

Methylmercury (MeHg) is a neurotoxic pollutant widely present in the environment. Initial symptoms of MeHg may include loss of body weight. However, the mechanisms by which MeHg induces body weight changes have yet to be fully elucidated.

Haloperidol Interactions with the dop-3 Receptor in Caenorhabditis elegans.

Haloperidol is a typical antipsychotic drug commonly used to treat a broad range of psychiatric disorders related to dysregulations in the neurotransmitter dopamine (DA). DA modulates important physiologic functions and perturbations in Caenorhabditis elegans (C. elegans) and, its signaling have been associated with alterations in behavioral, molecular, and morphologic properties in C.

The BXD21/TyJ recombinant inbred strain as a model for innate inflammatory response in distinct brain regions.

Oxidative stress and inflammatory cytokines affect the human brain, increasing the risk for mood and cognitive disorders. Such risk might be selective to brain-specific regions. Here, we determined whether BXD recombinant inbred (RI) mice strains are more suitable than C57BL/6J mice for the understanding of the relationship between antioxidant response and inflammatory responses.

Oxidative Stress in Methylmercury-Induced Cell Toxicity.

Methylmercury (MeHg) is a hazardous environmental pollutant, which elicits significant toxicity in humans. The accumulation of MeHg through the daily consumption of large predatory fish poses potential health risks, and the central nervous system (CNS) is the primary target of toxicity. Despite well-described neurobehavioral effects (i.

Methylmercury Affects the Expression of Hypothalamic Neuropeptides That Control Body Weight in C57BL/6J Mice.

Methylmercury (MeHg) is an environmental pollutant that affects primarily the central nervous system (CNS), causing neurological alterations. An early symptom of MeHg poisoning is the loss of body weight and appetite. Moreover, the CNS has an important role in controlling energy homeostasis.

BXD recombinant inbred strains participate in social preference, anxiety and depression behaviors along sex-differences in cytokines and tactile allodynia.

Depression and anxiety are the most common psychiatric disorders, representing a major public health concern. Dysregulation of oxidative and inflammatory systems may be associated with psychiatric disorders, such as depression and anxiety. Due to the need to find appropriate animal models to the understanding of such disorders, we queried whether 2 BXD recombinant inbred (RI) mice strains (BXD21/TyJ RI and BXD84/RwwJ RI mice) and C57BL/6 wild-type mice show differential performance in depression and anxiety related behaviors and biomarkers.

Muscular interleukin-6 differentially regulates skeletal muscle adaptation to high-fat diet in a sex-dependent manner.

Interleukin-6 (IL-6) is now known to be not only a major cytokine controlling the immune system but also basic physiological variables such as body weight and metabolism. We recently reported that muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner in mice. When compared with littermate floxed controls, males gained less weight whereas females gained more weight after a 12-week high-fat diet treatment (HFD).

Muscle-specific interleukin-6 deletion influences body weight and body fat in a sex-dependent manner.

Interleukin-6 (IL-6) is a major cytokine controlling not only the immune system but also basic physiological variables such as body weight and metabolism. While central IL-6 is clearly implicated in the latter, the putative role of peripheral IL-6 controlling body weight remains unclear. We herewith report results obtained in muscle-specific IL-6 KO (mIL-6 KO) mice.

Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6.

Interleukin (IL)-6 is crucial for the induction of many murine models of autoimmunity including experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. While IL-6-deficient mice (IL-6 KO) are resistant to EAE, we showed previously that in transgenic mice with astrocyte-targeted production of IL-6-restricted to the cerebellum (GFAP-IL6), EAE induced with MOG(35-55) was redirected away from the spinal cord to the cerebellum. To further establish the importance of IL-6 produced in the central nervous system, we have generated mice producing IL-6 essentially only in the brain by crossing the GFAP-IL6 mice with IL-6 KO mice.

Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior.

Interleukin-6 (IL-6) is a major cytokine which controls not only the immune system but also exhibits many other functions including effects in the central nervous system (CNS). IL-6 is known to be produced by different cells in the CNS, and all the major CNS do respond to IL-6, which makes it difficult to dissect the specific roles of each cell type when assessing the role of IL-6 in the brain. We have produced for the first time floxed mice for IL-6 and have crossed them with GFAP-Cre mice to delete IL-6 in astrocytes (Ast-IL-6 KO mice), and have compared their phenotype with that of mice with deletion of IL-6 receptor in astrocytes (Ast-IL6R KO mice).

Transgenic mice with astrocyte-targeted production of interleukin-6 are resistant to high-fat diet-induced increases in body weight and body fat.

Interleukin-6 (IL-6) is a major cytokine involved in both normal physiological brain functions and underlying significant neuropathology. IL-6 has been suggested to play a role in the control of body weight but the results are somewhat controversial. In this study we have challenged transgenic mice with astrocyte-targeted IL-6 expression (GFAP-IL6 mice) with a high-fat diet (55% kcal from fat) versus a control diet (10%).

Description of a novel panallergen of cross-reactivity between moulds and foods.

The present investigation is undertaken to demonstrate a novel cross-reactivity between aeroallergens (moulds fungi imperfecti) and allergens from foods (spinach and mushroom Agaricus bisporus). We have performed a dual study in vivo and in vitro, in a population of atopic patients. Data from in vivo tests performed with spinach and mushroom have been statistically analysed.

Role of the STAT1 pathway in apoptosis induced by fludarabine and JAK kinase inhibitors in B-cell chronic lymphocytic leukemia.

Signal transducers and activators of transcription (STAT) proteins comprise a family of transcription factors that have been implicated in tumoral transformation, especially in hematological malignancies. Because of this, the JAK/STAT pathway is attractive as a therapeutic target in these tumors. In the present study, we analyzed the ability of fludarabine and two JAK kinase inhibitors, AG490 and WHI-P131, to block STAT1 activation and induce apoptosis on B-cell chronic lymphocytic leukemia (B-CLL) cells.