Wintering Eiders Acquire Exceptional Se and Cd Burdens in the Bering Sea: Physiological and Oceanographic Factors

During late winter (March) in the Bering Sea, levels of Se in livers and Cd in kidneys of spectacled eiders Somateria fischeri were exceptionally high (up to 489 and 312 µg g−1 dry mass, respectively). Comparison of organ and blood samples during late winter, early spring migration, and breeding suggests that the eiders’ high Se and Cd burdens were accumulated at sea, with highest exposure during winter. High exposure may have resulted from high metabolic demands and food intake, as well as concentrations in food. In the eiders’ remote wintering area, their bivalve prey contained comparable Se levels and much higher Cd levels than in industrialized areas. Patterns of chlorophyll a in water and sediments indicated that phytoplankton detritus settling over a large area was advected into a persistent regional eddy, where benthic prey densities were higher than elsewhere and most eider foraging occurred. Se and Cd assimilated or adsorbed by bloom materials apparently also accumulated in the eddy, and were incorporated into the bivalve prey of eiders. Atmospheric deposition of dust-borne trace elements from Asia, which peaks during the ice-edge phytoplankton bloom from March to May, may augment processes that concentrate Se and Cd in eider prey. Compared with freshwater birds, some sea ducks (Mergini) accumulate much higher concentrations of trace elements, even with the same levels in food, with no apparent ill effects. Nevertheless, the absolute and relative burdens of different elements in sea ducks vary greatly among areas. Our results suggest these patterns can result from (1) exceptional accumulation and tolerance of trace elements when exposure is elevated by high food intake or levels in food, and (2) atmospheric and oceanographic processes that concentrate trace elements in local benthic food webs

CD8+ T-cell interferon-gamma production and proliferation is decreased in <i>T</i>. <i>gondii</i>-infected HD mice.

<p>HD and wild-type mice were injected ip with 100 <i>T</i>. <i>gondii</i> bradyzoites or vehicle at 5-weeks of age and sacrificed at 15 dpi. Cells were stimulated <i>ex-vivo</i> with <i>T</i>. <i>gondii</i> lysate to induce an antigen-specific response. Representative fluorescence histogram show IFN-γ production by CD8+ T-cells in spleen (<b>A</b>) and brain (<b>B</b>) in wild-type non-infected (gray filled), HD non-infected (gray-solid line), wild-type infected (black-solid line), and HD infected (black-dashed line) mice. Horizontal bars show the cutoff for IFN-γ positive cells. <b>C.</b> Absolute numbers of splenic CD8+ T-cells producing IFN-γ are decreased in infected HD mice. <b>D.</b> Absolute numbers of brain CD8+ T-cells producing IFN-γ are increased in both wild-type and infected HD mice. <b>E-H.</b> CD8+ cell proliferation in spleen and brain. Representative fluorescence histograms show relative Ki67 expression in CD8+ T-cells in the spleen (<b>E</b>) and brain (<b>F</b>). Colored line codes are as described above. Horizontal bars represent the cutoff for Ki67 positive cells. Infected HD mice have significantly decreased absolute numbers of proliferating CD8+ T-cells in spleen (<b>G</b>) and brain (<b>H</b>) compared to infected wild-type mice. Data points represent the average of technical duplicates from one experiment. White circles = wild-type, red circles = HD, white triangles = wild-type infected, red triangles = HD infected. P-values: * = <0.05, ** = <0.01, *** = <0.001.</p

Huntingtons Disease Mice Infected with <i>Toxoplasma gondii</i> Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality

<div><p>Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen <i>Toxoplasma gondii</i> (<i>T</i>. <i>gondii</i>) results in clinically silent life-long infection in immune-competent individuals. <i>T</i>. <i>gondii</i> infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and <i>T</i>. <i>gondii</i> infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early–advanced HD. <i>T</i>. <i>gondii</i> infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how <i>T</i>. <i>gondii</i> infection may interact with pathways mediating neurodegeneration in HD.</p></div

Brain IDO enzymatic activity is increased in early-advanced mouse HD.

<p><b>A.</b> Overview of brain IDO assay. Excess tryptophan is added to the brain extract and kynurenine is measured by HPLC-MS/MS. <b>B.</b> IDO activity is significantly increased in cerebral cortex and striatum (n = 10 wild-type and 12 HD mice combined from two independent experiments) of HD mice at 14-weeks of age corresponding to early-advanced HD [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162404#pone.0162404.ref021" target="_blank">21</a>]. <b>C.</b> Cortical IDO1 (but not IDO2) mRNA transcript is increased in HD mice. <b>D.</b> No significant difference was found in IDO1 and IDO2 mRNA levels in striatum of HD mice. <b>C-D.</b> Relative expression values were normalized to β-actin. n = 9 wild-type and 10 HD mice combined from two independent experiments. <b>B-D.</b> Bars represent means ± 95% confidence intervals. P-values: * = <0.05, *** = <0.001.</p

<i>T</i>. <i>gondii</i>-infected HD mice have elevated brain IDO activity.

<p>Wild-type and HD mice were infected around 5-weeks of age and sacrificed 15 days post-infection. <b>A.</b> IDO activity is increased in infected WT and HD cerebral cortex. <b>B-C.</b> Quantitative PCR for IDO1/2 transcripts in cortex. <b>B.</b> Cortical IDO1 transcript is increased in HD and wild-type infected mice. <b>C.</b> Cortical IDO2 transcript levels are not altered by HD or <i>T</i>. <i>gondii</i> infection. <b>D.</b> Infection increases IDO activity in striatum of both wild-type and HD mice. <b>E-F.</b> Quantitative PCR for IDO1/2 transcripts in striatum. <b>E.</b> Striatal IDO1 transcript is increased in HD mice compared to non-infected HD mice. <b>F.</b> Striatal IDO2 transcript levels are not altered by HD or <i>T</i>. <i>gondii</i> infection. <b>A&D.</b> Bars represent means ± 95% CI. Data was combined from two independent experiments, n = 9–11 mice. <b>B-C and E-F.</b> White circles = wild-type (n = 4), red circles = HD (n = 4), white triangles = wild-type infected (n = 5), red triangles = HD infected (n = 5) p-values: * = <0.05, ** = <0.01, *** = <0.001.</p

Parasite burden is increased in <i>T</i>. <i>gondii</i>-infected HD mice.

<p>Wild-type and HD mice were infected at 5-weeks of age and sacrificed at 15 dpi. <b>A.</b> Brain <i>T</i>. <i>gondii</i> cyst numbers are low consistent with transition from acute to chronic infection [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162404#pone.0162404.ref029" target="_blank">29</a>]. <b>B-C.</b> Parasite burden, assessed by PCR, in brain (B) and lung (C) is greater in infected HD as compared to infected wild-type mice. Parasites were not detected in spleen (<b>4D</b>) or liver (<b>4E</b>). <b>A-C.</b> Bars represent means ± SEM, n = 8 wild-type and n = 9 HD mice combined from two independent experiments. N.D. = not detected, p-values: * = <0.05, ** = <0.01, n.s. = not significant.</p