Dietary Anthocyanins Mitigate High-Fat Diet-Induced Hippocampal Inflammation in Mice.

Background: Obesity and consumption of high-fat diets (HFD) are associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote neuroinflammation. Inflammation can affect the hypothalamic pituitary adrenal (HPA) axis, which controls responses to stress and downregulates the brain-derived neurotrophic factor (BDNF), which can promote anxiety and depression, conditions frequently found in obesity. We previously showed that consumption of anthocyanins (AC) mitigate HFD-induced insulin resistance, intestinal permeability, and inflammation.

Oligodeoxynucleotide IMT504: Effects on Central Nervous System Repair Following Demyelination.

Multiple sclerosis (MS) is an immune-mediated central nervous system (CNS) disease characterized by demyelination resulting from oligodendrocyte loss and inflammation. Cuprizone (CPZ) administration experimentally replicates MS pattern-III lesions, generating an inflammatory response through microgliosis and astrogliosis. Potentially remyelinating agents include oligodeoxynucleotides (ODN) with a specific immunomodulatory sequence consisting of the active motif PyNTTTTGT.

Marginal Zinc Deficiency during Gestation and Lactation in Rats Affects Oligodendrogenesis, Motor Performance, and Behavior in the Offspring.

Background: Oligodendrocytes are responsible for myelin production in the central nervous system (CNS). Hypomyelination may slow saltatory nerve signal conduction and affect motor performance and behavior in adults. Gestational marginal zinc deficiency in rats significantly decreases proliferation of neural stem cells (NSCs) in the offspring brain.

Di-2-ethylhexyl phthalate affects zinc metabolism and neurogenesis in the developing rat brain.

We previously observed that developmental marginal zinc deficiency affects neurogenesis. Maternal phthalate exposure could disrupt fetal zinc homeostasis by triggering an acute phase response, causing maternal liver zinc retention that limits zinc availability to the fetus. Thus, we currently investigated whether exposure to di-2-ethylhexyl phthalate (DEHP) during gestation in rats alters fetal brain neurogenesis by impairing zinc homeostasis.

Gestational zinc deficiency impairs brain astrogliogenesis in rats through multistep alterations of the JAK/STAT3 signaling pathway.

We previously showed that zinc (Zn) deficiency affects the STAT3 signaling pathway in part through redox-regulated mechanisms. Given that STAT3 is central to the process of astrogliogenesis, this study investigated the consequences of maternal marginal Zn deficiency on the developmental timing and key mechanisms of STAT3 activation, and its consequences on astrogliogenesis in the offspring. This work characterized the temporal profile of cortical STAT3 activation from the mid embryonic stage up to young adulthood in the offspring from dams fed a marginal Zn deficient diet (MZD) throughout gestation and until postnatal day (P) 2.

Hexameric procyanidins inhibit colorectal cancer cell growth through both redox and non-redox regulation of the epidermal growth factor signaling pathway.

Dietary proanthocyanidins (PAC) consumption is associated with a decreased risk for colorectal cancer (CRC). Dysregulation of the epidermal growth factor (EGF) receptor (EGFR) signaling pathway is frequent in human cancers, including CRC. We previously showed that hexameric PAC (Hex) exert anti-proliferative and pro-apoptotic actions in human CRC cells.

Anthocyanins protect the gastrointestinal tract from high fat diet-induced alterations in redox signaling, barrier integrity and dysbiosis.

The gastrointestinal (GI) tract can play a critical role in the development of pathologies associated with overeating, overweight and obesity. We previously observed that supplementation with anthocyanins (AC) (particularly glycosides of cyanidin and delphinidin) mitigated high fat diet (HFD)-induced development of obesity, dyslipidemia, insulin resistance and steatosis in C57BL/6J mice. This paper investigated whether these beneficial effects could be related to AC capacity to sustain intestinal monolayer integrity, prevent endotoxemia, and HFD-associated dysbiosis.

Demyelination-remyelination in the Central Nervous System: Ligand-dependent Participation of the Notch Signaling Pathway.

Multiple sclerosis (MS) is an immune-mediated central nervous system disease mostly affecting young people. Multiple sclerosis and other neurodegenerative and white matter disorders involve oligodendrocyte (OL) damage and demyelination. Therefore, elucidating the signaling pathways involved in the remyelination process through the maturation of OL progenitor cells (OPCs) may contribute to the development of new therapeutic approaches.

Early Developmental Marginal Zinc Deficiency Affects Neurogenesis Decreasing Neuronal Number and Altering Neuronal Specification in the Adult Rat Brain.

During pregnancy, a decreased availability of zinc to the fetus can disrupt the development of the central nervous system leading to defects ranging from severe malformations to subtle neurological and cognitive effects. We previously found that marginal zinc deficiency down-regulates the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and affects neural progenitor cell (NPC) proliferation. This study investigated if marginal zinc deficiency during gestation in rats could disrupt fetal neurogenesis and affect the number and specification of neurons in the adult offspring brain cortex.

(-)-Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance.

Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD) is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (-)-epicatechin (EC) supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance.

TGF-β pro-oligodendrogenic effects on adult SVZ progenitor cultures and its interaction with the Notch signaling pathway.

Adult neural progenitor cells (NPCs) are capable of differentiating into neurons, astrocytes, and oligodendrocytes throughout life. Notch and transforming growth factor β1 (TGF-β) signaling pathways play critical roles in controlling these cell fate decisions. TGF-β has been previously shown to exert pro-neurogenic effects on hippocampal and subventricular zone (SVZ) NPCs in vitro and to interact with Notch in different cellular types.

Gestational marginal zinc deficiency impaired fetal neural progenitor cell proliferation by disrupting the ERK1/2 signaling pathway.

This study investigated if a marginal zinc deficiency during gestation in rats could affect fetal neural progenitor cell (NPC) proliferation through a down-regulation of the extracellular signal-regulated kinase (ERK1/2) signaling pathway. Rats were fed a marginally zinc-deficient or adequate diet from the beginning of gestation until embryonic day (E)19. The proportion of proliferating cells in the E19 fetal ventricular zone was decreased by marginal zinc deficiency.

(-)-Epicatechin reduces blood pressure increase in high-fructose-fed rats: effects on the determinants of nitric oxide bioavailability.

This work investigated the blood pressure (BP)-lowering effect of the flavanol (-)-epicatechin in a model of metabolic syndrome. Rats were fed a regular chow diet without (Control) or with 10% (w/v) fructose in the drinking water (high fructose, HF) for 8 weeks. A subgroup of the HF-fed rats was supplemented with (-)-epicatechin 20 mg/kg body weight (HF-EC).

Improving arylsulfatase activity determination in dried blood spots: Screening and diagnostic approaches for Maroteaux-Lamy syndrome (MPS VI).

Background: Mucopolysaccharidosis type VI can be screened by measuring the lysosomal arylsulfatase B (ARSB) residual enzyme activity in dried blood spots (DBS) using synthetic substrates. However, we have found experimental obstacles when determining ARSB activity with the fluorescent method due to the significant quenching effect rendered by DBS components.

Methods: We adapted the methods originally described by Chamoles et al.

GAP-43 slows down cell cycle progression via sequences in its 3'UTR.

Growth-associated protein 43 (GAP-43) is a neuronal phosphoprotein associated with initial axonal outgrowth and synaptic remodeling and recent work also suggests its involvement in cell cycle control. The complex expression of GAP-43 features transcriptional and posttranscriptional components. However, in some conditions, GAP-43 gene expression is controlled primarily by the interaction of stabilizing or destabilizing RNA-binding proteins (RBPs) with adenine and uridine (AU)-rich instability elements (AREs) in its 3'UTR.

Nutritional factors and aging in demyelinating diseases.

Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits.

The Notch signaling pathway: its role in focal CNS demyelination and apotransferrin-induced remyelination.

Oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Identifying the signaling pathways involved in myelin repair through oligodendroglial progenitor maturation is essential for the development of new therapies. This article investigated the role of the Notch signaling pathway in CNS demyelination and apotransferrin-induced remyelination in a focal lysolecithin-induced demyelination model in rats.

Blood pressure-lowering effect of dietary (-)-epicatechin administration in L-NAME-treated rats is associated with restored nitric oxide levels.

Epidemiological and intervention studies have shown that the intake of certain chocolates or cocoa products decreases blood pressure (BP) in humans. (-)-Epicatechin is the most abundant flavanol present in cocoa seeds and its derived foods. This work investigates the effects of dietary (-)-epicatechin on BP in rats that received N(ω)-nitro-l-arginine methyl ester (L-NAME) for 4 days.

Zinc deficiency and neurodevelopment: the case of neurons.

Zinc is essential for normal brain development. Gestational severe zinc deficiency can lead to overt fetal brain malformations. Although not teratogenic, suboptimal zinc nutrition during gestation can have long-term effects on the offspring's nervous system.

The role of zinc in the modulation of neuronal proliferation and apoptosis.

Although a requirement of zinc (Zn) for normal brain development is well documented, the extent to which Zn can modulate neuronal proliferation and apoptosis is not clear. Thus, we investigated the role of Zn in the regulation of these two critical events. A low Zn availability leads to decreased cell viability in human neuroblastoma IMR-32 cells and primary cultures of rat cortical neurons.

Sphingolipid metabolism is a crucial determinant of cellular fate in nonstimulated proliferating Madin-Darby canine kidney (MDCK) cells.

The present report was addressed to study the influence of sphingolipid metabolism in determining cellular fate. In nonstimulated proliferating Madin-Darby canine kidney (MDCK) cells, sphingolipid de novo synthesis is branched mainly to a production of sphingomyelin and ceramide, with a minor production of sphingosylphosphocholine, ceramide 1-phosphate, and sphingosine 1-phosphate. Experiments with (32)P as a radioactive precursor showed that sphingosine 1-phosphate is produced mainly by a de novo independent pathway.

Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells.

Although treatment of Hodgkin's lymphoma (HL) with a multi-drug approach has been very successful, its toxicity becomes evident after several years as secondary malignancies and cardiovascular disease. Therefore, the current goal in HL treatment is to find new therapies that specifically target the deregulated signaling cascades, such as NF-kappaB and STAT3, which cause Hodgkin and Reed-Sternberg (H-RS) cell proliferation and resistance of apoptosis. Based on the above information, we investigated the capacity of curcumin to inhibit NF-kappaB and STAT3 in H-RS cells, characterizing the functional consequences.

Dimeric procyanidin B2 inhibits constitutively active NF-kappaB in Hodgkin's lymphoma cells independently of the presence of IkappaB mutations.

Due to long-term toxicity of current Hodgkin's lymphoma (HL) treatment, the present challenge is to find new therapies that specifically target deregulated signaling cascades, including NF-kappaB, which are involved in Hodgkin (H) and Reed-Sternberg (RS) cell proliferation and resistance to apoptosis. We previously presented evidence that dimeric procyanidin B2 (B2) can interact with NF-kappaB proteins inhibiting the binding of NF-kappaB to DNA. Herein, we investigated if B2, acting at a late event in NF-kappaB signaling cascade, could be effective in inhibiting NF-kappaB in H-RS cells with different mechanisms of constitutive NF-kappaB activation.

Differential modulation of MAP kinases by zinc deficiency in IMR-32 cells: role of H(2)O(2).

The influence of zinc deficiency on the modulation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK1/2), p38, and c-Jun N-terminal kinase (JNK) was studied. Using human IMR-32 cells as a model of neuronal cells, the role of oxidants on MAPKs and activator protein-1 (AP-1) activation in zinc deficiency was investigated, characterizing the participation of these events in the triggering of apoptosis. Relative to controls, cells incubated in media with low zinc concentrations showed increased cell oxidants and hydrogen peroxide (H(2)O(2)) release, increased JNK and p38 activation, high nuclear AP-1-DNA binding activity, and AP-1-dependent gene expression.

Corticosterone down-regulates dopamine D4 receptor in a mouse cerebral cortex neuronal cell line.

We have previously reported that restraint stress applied to the gestant mother results in long-lasting effects in the offspring that show an increase in the number of dopamine D2-type receptors in limbic areas on the adult rat brain cortex. Evidence that stress during pregnancy results in activation of the hypothalamic-pituitary-adrenal (HPA) axis has been extensively demonstrated. Therefore, high levels of corticosterone secreted in response to stress by the gestant mother might be one of the predisposing factors for the changes observed in dopamine receptors in the adult rat brain.