Tryptophan overloading activates brain regions involved with cognition, mood and anxiety

Tryptophan is the only precursor of serotonin and mediates serotonergic activity in the brain. Previous studies have shown that the administration of tryptophan or tryptophan depletion significantly alters cognition, mood and anxiety. Nevertheless, the neurobiological alterations that follow these changes have not yet been fully investigated. The aim of this study was to verify the effects of a tryptophan-enriched diet on immunoreactivity to Fos-protein in the rat brain. Sixteen male Wistar rats were distributed into two groups that either received standard chow diet or a tryptophan-enriched diet for a period of thirty days. On the morning of the 31st day, animals were euthanized and subsequently analyzed for Fos-immunoreactivity (Fos-ir) in the dorsal and median raphe nuclei and in regions that receive serotonin innervation from these two brain areas. Treatment with a tryptophan-enriched diet increased Fos-ir in the prefrontal cortex, nucleus accumbens, paraventricular hypothalamus, arcuate and ventromedial hypothalamus, dorsolateral and dorsomedial periaqueductal grey and dorsal and median raphe nucleus. These observations suggest that the physiological and behavioral alterations that follow the administration of tryptophan are associated with the activation of brain regions that regulate cognition and mood/anxiety-related responses.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Univ Fed Sao Paulo, Dept Psicobiol, Rua Napoleao Barros 925,3 Andar, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biociencias, Rua Silva Jardim 136,3 Andar, BR-11060001 Santos, SP, BrazilUniv Fed Sao Paulo, Dept Psicobiol, Rua Napoleao Barros 925,3 Andar, BR-04023062 Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Dept Biociencias, Rua Silva Jardim 136,3 Andar, BR-11060001 Santos, SP, BrazilWeb of Scienc

Influência da restrição calórica crônica em marcadores de estresse oxidativo, morte e sobrevivência em áreas encefálicas relacionadas ao comportamento alimentar em camundongos de meia-idade

O comportamento alimentar depende da integração de sinalização homeostática e hedônica no sistema nervoso central. Neurônios sofrem com o estresse oxidativo e redução de fatores neurotróficos no envelhecimento, o que pode levar à morte celular. Entretanto, a restrição calórica (RC) na maturidade é conhecida por seu efeito neuroprotetor, por reduzir o estresse oxidativo e propiciar a longevidade. Objetivo: avaliar como a RC afeta áreas encefálicas responsáveis pelo comportamento alimentar em camundongos no início da meia-idade. Métodos: Quantificação de ΔFosB (atividade neuronal), Bcl2 (sobrevivência celular), Caspase 3 (morte celular), BDNF (neuroproteção) e 8OHgG (estresse oxidativo) por imunohistoquímica, nas áreas do comportamento alimentar homeostático (núcleo arqueado, paraventricular, ventromedial, dorsomedial do hipotálamo e área hipotalâmica lateral) e hedônico (área tegmental ventral, núcleo accumbens, córtex orbito frontal e cingulado) em camundongos C57BL/6 jovens e de meia-idade submetidos ou não à RC de 30%. Resultados: A massa corporal dos animais que passaram por RC até meia-idade não foi diferente dos animais jovens controles e restritos. O efeito da idade (p<0.05) se sobrepôs ao da RC na maior parte das áreas estudadas, levando ao aumento da expressão de Bcl2 (núcleo arqueado, paraventricular, ventromedial, dorsomedial, área lateral do hipotálamo, núcleo accumbens e área ventral tegmental), Caspase 3 (núcleo ventromedial e dorsomedial, córtex orbitofrontal e área tegmental ventral) e 8OHdG (núcleo paraventricular do hipotálamo e córtex cingulado) em relação aos animais jovens. A restrição foi capaz de aumentar (p<0.05) a expressão de Caspase 3 no córtex do cingulado e Bcl2 no núcleo dorsomedial do hipotálamo comparada aos grupos não restritos. Conclusão: O efeito da idade se sobrepôs ao da RC, que não evidenciou efeitos expressivos na ativação neuronal, estresse oxidativo, e marcadores de morte e sobrevivência celular nas áreas homeostáticas e hedônicas do comportamento alimentar dos animais de meia-idade. Contudo, a RC se mostrou uma intervenção segura, sem efeitos negativos nesses mesmos marcadores nas áreas avaliadas.Feeding behavior depends on the integration of homeostatic and hedonic signaling in the central nervous system. Neurons suffer from oxidative stress and reduction of neurotrophic factors in aging, which can lead to cell death. However, caloric restriction (CR) at maturity is known for its neuroprotective effect, as it reduces oxidative stress and promotes longevity. Objective: to evaluate how the CR affects brain areas responsible for feeding behavior in mice in early middle age. Methods: Quantification of ΔFosB (neuronal activity), Bcl2 (cell survival), Caspase 3 (cell death), BDNF (neuroprotection), and 8OHgG (oxidative stress) by immunohistochemistry, in the areas of homeostatic (arcuate nucleus, paraventricular, ventromedial, dorsomedial hypothalamus, and lateral hypothalamic area) and hedonic (ventral tegmental area, nucleus accumbens, orbitofrontal and cingulate cortex) feeding behavior in young and middle-aged C57BL/6 mice submitted or not to 30% CR. Results: The body mass of animals that underwent CR until middle age was not different from young control and restricted animals. The effect of age (p<0.05) overlapped that of CR in most areas studied, leading to increased expression of Bcl2 (arcuate nucleus, paraventricular, ventromedial, dorsomedial, lateral area of the hypothalamus, nucleus accumbens, and ventral tegmental area), Caspase 3 (ventromedial and dorsomedial nucleus, orbitofrontal cortex and ventral tegmental area) and 8OHdG (paraventricular nucleus of the hypothalamus and cingulate cortex) in relation to young animals. The restriction increased (p<0.05) the expression of Caspase 3 in the cingulate cortex and Bcl2 in the dorsomedial nucleus of the hypothalamus compared to the non-restricted groups. Conclusion: The effect of age overlapped that of CR, which did not show significant effects on neuronal activation, oxidative stress, cell death, and survival markers in the homeostatic and hedonic areas of the feeding behavior of middle-aged animals. However, CR proved to be a safe intervention, with no negative effects on these same markers in the assessed areas.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Pâncreas Artificial: Uma revisão Sobre Modelos e Técnicas Automatizadas de Administração de Insulina

&lt;p&gt;Alcançar um controle glicêmico ideal é um grande desafio para pacientes com Diabetes Mellitus (DM), principalmente devido à insuficiência, tanto na secreção quanto na ação da insulina. Nesse contexto, o uso de sistemas de pâncreas artificial, também conhecidos como controle fechado de glicose, surge como uma alternativa em ascensão. Essa abordagem combina uma bomba de insulina, um monitoramento contínuo de glicose, integrados a um mecanismo de controle algorítmico, para fornecer insulina de forma responsiva com base nos níveis de glicose. Este artigo explora esses componentes que proporcionaram avanços no desenvolvimento de dispositivos de pâncreas artificial. Para isso, são apresentadas as particularidades de cada um, evidenciando sua evolução e estruturação, apoiado em diversos estudos que têm revelado resultados promissores.&lt;/p&gt

β-Glucan induces reactive oxygen species production in human neutrophils to improve the killing of Candida albicans and Candida glabrata isolates from vulvovaginal candidiasis.

Vulvovaginal candidiasis (VVC) is among the most prevalent vaginal diseases. Candida albicans is still the most prevalent species associated with this pathology, however, the prevalence of other Candida species, such as C. glabrata, is increasing. The pathogenesis of these infections has been intensely studied, nevertheless, no consensus has been reached on the pathogenicity of VVC. In addition, inappropriate treatment or the presence of resistant strains can lead to RVVC (vulvovaginal candidiasis recurrent). Immunomodulation therapy studies have become increasingly promising, including with the β-glucans. Thus, in the present study, we evaluated microbicidal activity, phagocytosis, intracellular oxidant species production, oxygen consumption, myeloperoxidase (MPO) activity, and the release of tumor necrosis factor α (TNF-α), interleukin-8 (IL-8), IL-1β, and IL-1Ra in neutrophils previously treated or not with β-glucan. In all of the assays, human neutrophils were challenged with C. albicans and C. glabrata isolated from vulvovaginal candidiasis. β-glucan significantly increased oxidant species production, suggesting that β-glucan may be an efficient immunomodulator that triggers an increase in the microbicidal response of neutrophils for both of the species isolated from vulvovaginal candidiasis. The effects of β-glucan appeared to be mainly related to the activation of reactive oxygen species and modulation of cytokine release

Microbicidal activity of β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i>.

<p>Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and incubated with the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (RVVC, VVC, and ASS; 2.0×10⁷ CFU/ml) at 37°C for different times (0, 30, 60, 90, and 120 min). The quantity of viable yeast was estimated by plating the samples in Sabouraund Dextrose Agar (SDA) at 37°C for 24 h. The data are expressed as the mean ± SD of three separate experiments. <b>*</b><i>p</i>≤0.05, significant difference compared with the control group (yeast alone); <b>^#</b><i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils.</p

Cytokine release by β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i>.

<p>Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and activated or not by the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (RVVC, VVC, and ASS; 2.0×10⁷ CFU/ml) and 1 µg/ml LPS and cultured for 18 h. (a, a’) IL-8. (b, b’) IL-1β. (c, c’) IL-1Ra. (d, d’) TNF-α. The data are expressed as the mean ± SD of three independent experiments. *<i>p</i>≤0.05, significant difference compared with the control group (neutrophils alone); ^#<i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils.</p

Oxygen consumption by β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i>.

<p>Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and activated or not by the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (RVVC, VVC, and ASS; 2.0×10⁷ CFU/ml). Oxygen consumption was monitored for 5–10 min and calculated from the polarographic recordings using an initial concentration of dissolved oxygen of 190 µM at 37°C. The data are expressed as the mean ± SD of three independent experiments. *<i>p</i>≤0.05, significant difference compared with the control group (neutrophils alone); ^#<i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils.</p

Phagocytosis activity of β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i>. Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and incubated for 1 h at 37°C with the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (RVVC, VVC, and ASS; 2.0×10⁷ CFU/ml) labeled with FITC.

<p>Phagocytosis was determined by flow cytometry, and the results are expressed as the mean fluorescence (in arbitrary units [au]) ± SD of three independent experiments. <b>^#</b><i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils.</p

Myeloperoxidase activity of β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i> (integrated light emission).

<p>The inset represents kinetic study of MPO activity of β-glucan-treated neutrophils after 20 minutes of incubation. Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and incubated with the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (2×10⁷ CFU/ml) for 30 min. (a,a’) ATCC. (b,b’) ASS. (c,c’) VVC. (d,d’) RVVC. After incubation, chemiluminescence was monitored for 20 min at 37°C in a microplate luminometer using luminol as a chemical light amplifier. The data are expressed as the mean ± SD of three independent experiments. *<i>p</i>≤0.05, significant difference compared with the control group (neutrophils alone); ^#<i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils.</p

Intracellular oxidant species production by β-glucan-treated neutrophils activated by different isolates of <i>C. albicans</i> and <i>C. glabrata</i> determined by flow cytometry.

<p>Neutrophils (2.0×10⁶ cells/ml) were previously treated or not with 3 mg/ml β-glucan and incubated for 1 h with the reference strain and different isolates of (A) <i>C. albicans</i> and (B) <i>C. glabrata</i> (RVVC, VVC, and ASS; 2.0×10⁷ CFU/ml), followed by 30 min incubation with DHR. The data are expressed as the mean ± SD of at least three independent experiments. <b>*</b><i>p</i>≤0.05, significant difference compared with the control group (neutrophils alone); ^#<i>p</i>≤0.05, significant difference compared with untreated and activated neutrophils. (C and D) Representative dot plot display of FL1 (green fluorescence) <i>vs</i>. FL2 on a logarithmic scale. (C – (a) ATCC, (c) ASS, (e) VVC,(g) RVVC) <i>C. albicans</i> with untreated neutrophils. (C – (b) ATCC,(d) ASS,(f) VVC,(h) RVVC) <i>C. albicans</i> with neutrophils previously treated with 3 mg/ml β-glucan. (D – (a’) ATCC,(c’) ASS,(e’) VVC,(g’) RVVC) <i>C. glabrata</i> with untreated neutrophils. (D – (b’) ATCC,(d’) ASS,(f’) VVC,(h’) RVVC) <i>C. glabrata</i> with neutrophils previously treated with 3 mg/ml β-glucan.</p