Susana Roque | Universidade do Minho (original) (raw)

Papers by Susana Roque

Neurology® neuroimmunology & neuroinflammation, 2015

Immunosenescence and cognitive decline are common markers of the aging process. Taking into consi... more Immunosenescence and cognitive decline are common markers of the aging process. Taking into consideration the heterogeneity observed in aging processes and the recently described link between lymphocytes and cognition, we herein explored the possibility of an association between alterations in lymphocytic populations and cognitive performance. In a cohort of cognitively healthy adults (n = 114), previously characterized by diverse neurocognitive/psychological performance patterns, detailed peripheral blood immunophenotyping of both the innate and adaptive immune systems was performed by flow cytometry. Better cognitive performance was associated with lower numbers of effector memory CD4(+) T cells and higher numbers of naive CD8(+) T cells and B cells. Furthermore, effector memory CD4(+) T cells were found to be predictors of general and executive function and memory, even when factors known to influence cognitive performance in older individuals (e.g., age, sex, education, and mood...

Cardiovasc Psychiatry Neurol, 2009

An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, nam... more An increasing body of evidence implicates proinflammatory cytokines in psychiatric disorders, namely, in depression. Of notice, recent studies showed that anti-inflammatory cytokines, such as IL-10, also modulate depressive-like behavior. In this article, we propose that the anti-inflammatory cytokine IL-10 is a putative link between two of the most widely reported phenomenon observed in depressed patients: the disruption of the hypothalamic-pituitary-adrenal axis and the imbalanced production of cytokines. If so, IL-10 might represent a novel target for antidepressant therapy.

Journal of immunology (Baltimore, Md. : 1950), 2010

The ability of the thymus to generate a population of T cells that is, for the most part, self-re... more The ability of the thymus to generate a population of T cells that is, for the most part, self-restricted and self-tolerant depends to a great extent on the Ags encountered during differentiation. We recently showed that mycobacteria disseminate to the thymus, which raised the questions of how mycobacteria within the thymus influence T cell differentiation and whether such an effect impacts host-pathogen interactions. Athymic nude mice were reconstituted with thymic grafts from Mycobacterium avium-infected or control noninfected donors. T cells generated from thymi of infected donors seemed generally normal, because they retained the ability to reconstitute the periphery and to respond to unspecific stimuli in vitro as well as to antigenic stimulation with third-party Ags, such as OVA, upon in vivo immunization. However, these cells were unable to mount a protective immune response against a challenge with M. avium. The observation that thymic infection interferes with T cell differ...

Frontiers in Behavioral Neuroscience, 2014

Mesquita have contributed equally to this work.

Frontiers in Behavioural Neuroscience, 2011

Glucocorticoids, namely dexamethasone, are prescribed during late gestation in pregnancies at ris... more Glucocorticoids, namely dexamethasone, are prescribed during late gestation in pregnancies at risk of originating premature newborns, to promote fetal lung maturation. However, adverse early life events have been reported to induce long-lasting changes in the immune and central nervous systems. The accumulating evidence on bidirectional interactions between both systems in psychiatric disorders like depression, prompted us to further investigate the long-term impact of prenatal dexamethasone administration in depressive-like behavior, the immune system and in the ability to mount an immune response to acute infection. The adult male offspring of pregnant dams treated with dexamethasone present depressive-like behavior concomitant with a decrease in CD8(+) T lymphocytes and an increase in B and CD4(+) regulatory T cells. This is accompanied by lower levels of serum interleukin-6 (IL-6) and IL-10. Despite of these differences, when spleen cells are stimulated, in vitro, with lipopolysaccharide, those from adult rats prenatally treated with dexamethasone display a stronger pro-inflammatory cytokine response. However, this immune system profile does not hamper the ability of rats prenatally treated with dexamethasone to respond to acute infection by Listeria monocytogenes. Of notice, L. monocytogenes infection triggers depressive-like behavior in control animals but does not worsen that already present in dexamethasone-treated animals. In summary, prenatal administration of dexamethasone has long-lasting effects on the immune system and on behavior, which are not further aggravated by acute infection with L. monocytogenes.

Thyroid, 2010

Background: The thyroid hormone milieu is of crucial importance for the developing fetus. Pregnan... more Background: The thyroid hormone milieu is of crucial importance for the developing fetus. Pregnancy induces physiological changes in thyroid homeostasis that are influenced by the iodine status. However, longitudinal studies addressing thyroid function during pregnancy and after delivery are still lacking in mild-to-moderate iodine-deficient populations. Here we characterize the serum parameters of thyroid function throughout pregnancy, and until 1 year after delivery, in a population of pregnant women whom we have previously reported to be iodine deficient (median urinary iodine levels below 75 mg/L). Methods: One hundred eighteen pregnant women were studied. Clinical data were recorded and serum was collected. Serum total and free thyroxine (T 4 ) and triiodothyronine (T 3 ), thyroid-stimulating hormone, thyroxinebinding globulin, and thyroglobulin were measured. Results: Mean total T 4 ranged from 159 at the start of gestation to 127 nmol/L at 1 year after delivery, free T 4 from 14.2 to 17.8 pmol/L, total T 3 from 2.4 to 2.1 nmol/L, free T 3 from 6.7 pmol/L to 6.4 pmol/L, thyroidstimulating hormone from 1.2 to 1.4 mIU/L, T 4 -binding globulin from 62.0 to 26.9 mg/L, and thyroglobulin from 11 to 10 mg/L. Conclusion: The pregnant women in this study had an absence of the usual free T 4 spike and a smaller than expected increment in total T 4 , described during pregnancy in iodine-sufficient populations. A greater number of women had subclinical hypothyroidism compared with iodine-sufficient populations. This hormonal profile, most likely due to iodine insufficiency, may result in inadequate thyroid hormone supply to the developing fetus. We conclude that care should be taken when reviewing the results of thyroid hormone tests in iodineinsufficient populations and when no gestation-specific reference values have been established. In addition, we recommend iodine supplementation in our population and populations with similar iodine status, particularly during pregnancy and lactation.

Microbes and Infection, 2007

Mycobacterial infections are among the major health threats worldwide. Ability to fight these inf... more Mycobacterial infections are among the major health threats worldwide. Ability to fight these infections depends on the host's immune response, particularly on macrophages and T lymphocytes produced by the thymus. Using the mouse as a model, and two different routes of infection (aerogenic or intravenous), we show that the thymus is consistently colonized by Mycobacterium tuberculosis, Mycobacterium avium or Mycobacterium bovis BCG. When compared to organs such as the liver and spleen, the bacterial load reaches a plateau at later time-points after infection. Moreover, in contrast with organs such as the spleen and the lung no granuloma were found in the thymus of mice infected with M. tuberculosis or M. avium. Since T cell differentiation depends, to a large extent, on the antigens encountered within the thymus, infection of this organ might alter the host's immune response to infection. Therefore, from now on, the thymus should be considered in studies addressing the immune response to mycobacterial infection.

Journal of Psychiatric Research, 2008

The role of pro-inflammatory cytokines in psychiatric disorders has been the focus of great resea... more The role of pro-inflammatory cytokines in psychiatric disorders has been the focus of great research attention in recent years. Para-11 doxically, the same is not true for anti-inflammatory cytokines. In the present study, we assessed the behavioral profile of animals with 12 altered expression of the anti-inflammatory cytokine IL-10. 13 We performed a battery of tests to assess anxiety, depressive-like and cognitive behaviors in mice overexpressing IL-10 (PMT10) and 14 IL-10 À/À animals; in the later mice we also tested the behavioral effect of IL-10 administration. 15 In the forced-swimming test, IL-10 À/À females displayed increased depressive-like behavior; importantly, this phenotype was reverted 16 by the injection of IL-10. Moreover, mice overexpressing IL-10 presented a decreased depressive-like behavior. Despite the presence of a 17 similar trend, male animals did not reach significant differences in depressive-like behavior. Assessment in the open-field showed that the 18 absence of IL-10 decreased the percentage of time spent in the center of the arena in both male and female mice, while male animals 19

The Journal of Immunology, 2007

Increased production of IL-10 has been frequently associated with augmented susceptibility to inf... more Increased production of IL-10 has been frequently associated with augmented susceptibility to infection. However, the correlation between IL-10 activity and susceptibility to mycobacterial infection is still uncertain. Although studies using transgenic mice overexpressing IL-10 consistently showed an increased susceptibility to mycobacterial infection, experimental approaches in which IL-10 activity was reduced or abrogated originated inconclusive data. We show here that this controversy might be due to the mouse strains used in the various experimental procedures. Our results show that BALB/c mice are more susceptible than C57BL/6 to Mycobacterium avium infection. This increased susceptibility of BALB/c mice is, to a great extent, due to distinct activity of IL-10 between the two mouse strains. In accordance, reduction of IL-10 activity through the administration of anti-IL-10R mAb, or the absence of IL-10 as studied in IL-10 knockout mice, clearly decreased the susceptibility of BALB/c mice to M. avium but had a less obvious effect in C57BL/6 mice. Moreover, abrogation of IL-10 activity in infected BALB/c mice increased the efficacy of antimycobacterial therapy, whereas for the C57BL/6 mice it produced no effect. These observations show that the activity of IL-10 in response to the same mycobacterial stimulus influences not only the susceptibility to infection but also the efficacy of antimycobacterial therapy. This should now be considered in the context of human response to mycobacterial infection, particularly as a possible strategy to improve treatment against infections by mycobacteria.

Journal of Bioactive and Compatible Polymers, 2011

Carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles, comprised of a PAMA... more Carboxymethylchitosan/poly(amidoamine) (CMCht/PAMAM) dendrimer nanoparticles, comprised of a PAMAM dendrimer core grafted with chains of CMCht, have recently been proposed for intracellular drug delivery. In previous reports, these nanoparticles had lower levels of cytotoxicity when compared with traditional dendrimers. In this study, the short-term in vivo biodistribution of fluorescein isothiocyanate (FITC)-labeled CMCht/PAMAM dendrimer nanoparticles after intravenous (IV) injections in Wistar Han rats was determined. The brain, liver, kidney, and lung were collected at 24, 48, and 72 h after injection and stained with phalloidin-tetramethylrhodamine isothiocyanate (TRITC, red) and 4′,6-diamidino-2-phenylindole dihydrochloride (DAPI, blue) to trace the nanoparticles within these tissues. The liver, kidney, and lung were also stained for hematoxylin and eosin to assess any morphological alterations of these organs. CMCht/PAMAM dendrimer nanoparticles were observed within the vascular space and parenchyma of liver, kidney, and lung and in the choroid plexus, after each injection period. No particles were observed in the

Frontiers in Neuroscience, 2009

Brain, Behavior, and Immunity, 2011

Frontiers in psychiatry, 2015

Exposure to chronic stress can have broad effects on health ranging from increased predisposition... more Exposure to chronic stress can have broad effects on health ranging from increased predisposition for neuropsychiatric disorders to deregulation of immune responses. The chronic unpredictable stress (CUS) protocol has been widely used to study the impact of stress exposure in several animal models and consists in the random, intermittent, and unpredictable exposure to a variety of stressors during several weeks. CUS has consistently been shown to induce behavioral and immunological alterations typical of the chronic stress-response. Unfortunately C57BL/6 mice, one of the most widely used mouse strains, due to the great variety of genetically modified lines, seem to be resistant to the commonly used 4-week-long CUS protocol. The definition of an alternative CUS protocol allowing the use of C57BL/6 mice in chronic stress experiments is a need. Here, we show that by extending the CUS protocol to 8 weeks is possible to induce a chronic stress-response in C57BL/6 mice, as revealed by abr...