Copper disrupts S-nitrosothiol signaling in activated BV2 microglia.

Microglia, the primary resident immune cells of the central nervous system (CNS), responds rapidly to pathogens and injury by secreting immune mediators including nitric oxide (NO). The reaction of NO with the anti-oxidant glutathione forms S-nitrosoglutathione (GSNO), the major pool of biologic NO in the body. GSNO is degraded by GSNO reductase (GSNOR).

Immunofluorescent detection of S-nitrosoproteins in cell culture.

The role of S-nitrosylation in cellular signaling has been clearly demonstrated. There a number of mechanisms whereby this post-translational modification can occur and the number of protein targets continue to expand. The need to be able to monitor when this important signaling process occurs within cells is increasingly important.

Copper modulates the phenotypic response of activated BV2 microglia through the release of nitric oxide.

Microglia are resident immune cells of the central nervous system. Their persistent activation in neurodegenerative diseases, traditionally attributed to neuronal dysfunction, may be due to a microglial failure to modulate the release of cytotoxic mediators such as nitric oxide (NO). The persistent activation of microglia with the subsequent release of NO vis-á-vis the accumulation of redox transition metals such as copper (Cu) in neurodegenerative diseases, prompted the hypothesis that copper would alter NO signaling by changing the redox environment of the cell and that, by altering the fate of NO, microglia would adopt a different phenotype.

Interactions of lifetime lead exposure and stress: behavioral, neurochemical and HPA axis effects.

Lead (Pb) and stress co-occur as risk factors, share biological substrates and produce common adverse effects. We previously found that prenatal restraint stress (PS) or offspring stress (OS) could enhance maternal Pb-induced behavioral, brain neurotransmitter level and HPA axis changes. The current study examined how lifetime Pb exposure, consistent with human environmental exposure, interacts with stress.

Experimental manipulations blunt time-induced changes in brain monoamine levels and completely reverse stress, but not Pb+/-stress-related modifications to these trajectories.

This study sought to further understand how environmental conditions influence the outcomes of early developmental insults. It compared changes in monoamine levels in frontal cortex, nucleus accumbens and striatum of male and female Long-Evans rat offspring subjected to maternal Pb exposure (0, 50 or 150ppm in drinking water from 2 months pre-breeding until pup weaning)+/-prenatal (PS) (restraint on GD16-17) or PS+offspring stress (OS; three variable stress challenges to young adults) determined at 2 months of age and at 6 months of age in littermates subsequently exposed either to experimental manipulations (EM: daily handling and performance on an operant fixed interval (FI) schedule of food reward), or to no experience (NEM; time alone). Time alone (NEM conditions), even in normal (control) animals, modified the trajectory of neurochemical changes between 2 and 6 months across brain regions and monoamines.

Alterations in glucocorticoid negative feedback following maternal Pb, prenatal stress and the combination: a potential biological unifying mechanism for their corresponding disease profiles.

Combined exposures to maternal lead (Pb) and prenatal stress (PS) can act synergistically to enhance behavioral and neurochemical toxicity in offspring. Maternal Pb itself causes permanent dysfunction of the body's major stress system, the hypothalamic pituitary adrenal (HPA) axis. The current study sought to determine the potential involvement of altered negative glucocorticoid feedback as a mechanistic basis of the effects in rats of maternal Pb (0, 50 or 150 ppm in drinking water beginning 2 mo prior to breeding), prenatal stress (PS; restraint on gestational days 16-17) and combined maternal Pb+PS in 8 mo old male and female offspring.

Influence of low level maternal Pb exposure and prenatal stress on offspring stress challenge responsivity.

We previously demonstrated potentiated effects of maternal Pb exposure producing blood Pb(PbB) levels averaging 39microg/dl combined with prenatal restraint stress (PS) on stress challenge responsivity of female offspring as adults. The present study sought to determine if: (1) such interactions occurred at lower PbBs, (2) exhibited gender specificity, and (3) corticosterone and neurochemical changes contributed to behavioral outcomes. Rat dams were exposed to 0, 50 or 150ppm Pb acetate drinking water solutions from 2 mos prior to breeding through lactation (pup exposure ended at weaning; mean PbBs of dams at weaning were <1, 11 and 31microg/dl, respectively); a subset in each Pb group underwent prenatal restraint stress (PS) on gestational days 16-17.

CNS effects of developmental Pb exposure are enhanced by combined maternal and offspring stress.

Lead (Pb) exposure and elevated stress are co-occurring risk factors. Both impact brain mesolimbic dopamine/glutamate systems involved in cognitive functions. We previously found that maternal stress can potentiate Pb-related adverse effects in offspring at blood Pb levels averaging approximately 40 microg/dl.

Lifetime consequences of combined maternal lead and stress.

Elevated lead (Pb) exposure and high stress both target low socio-economic status populations. Both also act on the hypothalamic-pituitary-adrenal (HPA) axis. Pb disrupts cognition through effects on the mesocorticolimbic dopamine pathway.

New and evolving concepts in the neurotoxicology of lead.

Lead (Pb) is a xenobiotic metal with no known essential function in cellular growth, proliferation, or signaling. Decades of research characterizing the toxicology of Pb have shown it to be a potent neurotoxicant, especially during nervous system development. New concepts in the neurotoxicology of Pb include advances in understanding the mechanisms and cellular specificity of Pb.

Neuronal, endocrine, and anorexic responses to the T-cell superantigen staphylococcal enterotoxin A: dependence on tumor necrosis factor-alpha.

Staphylococcal enterotoxin A (SEA) is a microbial superantigen that activates T-lymphocytes and induces production of various cytokines, including tumor necrosis factor-alpha (TNFalpha). Previously, it was shown that SEA activates the hypothalamic-pituitary-adrenal axis and augments gustatory neophobic behaviors. In the present study, it was hypothesized that these effects involve neuronal activation in forebrain regions mediating fear and/or anxiety and are dependent on the production of TNFalpha.

Effects of bacterial superantigens on behavior of mice in the elevated plus maze and light-dark box.

Bacterial superantigens, such as staphylococcal enteroxins A and B (SEA/SEB) stimulate T cells to produce high levels of cytokines in blood. Previously it had been shown that these toxins were capable of stimulating increased neuroendocrine activity and enhanced behavioral reactivity to novel gustatory and non-gustatory stimuli. Therefore, it was suggested that these superantigens may promote anxiety-like behavior.

Stressor-induced modulation of immune function: a review of acute, chronic effects in animals.

The present paper reviews recent studies on the effects of stress on immune function in laboratory animals. The emphasis is on those studies where a simultaneous comparison of acute and chronic stress regimens was determined, although additional relevant studies are also reviewed. The effects of stress on basic measurements of cellular and humoral immune measures are discussed, including the growing number of studies that have reported alterations in macrophage functions.

Dissipation of retroactive interference in human infants.

In 3 experiments with 85 human 3-month-olds, the authors asked whether retroactive interference with their memory of the original training stimulus is temporary or permanent. Infants learned to move a mobile by kicking and then were exposed to a different mobile (Experiment 1) or context (Experiment 2) immediately or 3 days afterward (Experiment 3). They were tested after increasing delays with the original stimulus, the exposed stimulus, or a completely novel stimulus.

The development of explicit memory for basic perceptual features.

In three experiments with 164 individuals between 4 and 80 years old, we examined age-related changes in explicit memory for three perceptual features--item identity, color, and location. In Experiments 1-2, feature recognition was assessed in an incidental learning, gamelike task resembling the game Concentration. In Experiment 3, feature recognition was assessed using a pencil-and-paper task after intentional learning instructions.

Potentiation of interleukin-1beta adjuvant effects on the humoral immune response to antigen in adrenalectomized mice.

Objectives: Activation of the hypothalamic-pituitary-adrenal (HPA) axis is a primary effect of interleukin-1 (IL-1), with elevated glucocorticoids considered a mechanism for negative feedback immunoregulation. However, there is little direct evidence of such a functional relationship between IL-1-mediated immunoregulation and neuroendocrine influences elicited by IL-1. Therefore, the goal of this study was to examine whether the known adjuvant effects of IL-1 are altered in the absence of neuroendocrine feedback due to adrenalectomy.

Retroactive interference in 3-month-old infants.

Three experiments assessed the effect of the similarity and timing of interpolated information on retroactive interference in human infants. After 3-month-olds learned to move a mobile (the cue) in a distinctive context by kicking, they were exposed to novel stimuli and were tested 24 hr later for recognition of their training stimuli. In Experiment 1, the interpolated cue, context, or both were novel.