Este estudo tem como objetivo estudar o fósforo total e as especiações de fósforo nos sedimentos superficiais associados aos processos biogeoquímicos em dois sistemas estuarinos, na plataforma continental sudeste e na região polar antártica. Amostras de água de fundo foram coletadas em dois períodos sazonais (verão-inverno) nos estuários sob diferentes graus de impacto ambiental antrópico. A metodologia de extração das frações de (SEDEX) aplicada para obter as especiações químicas de fósforo foi testada com padrões certificados antes das análises. Os resultados foram reprodutivos e a eficiência da extração foi aceitável. As concentrações das espécies químicas de fósforo sedimentar nos dois estuários mostraram diferenças entre os setores seguindo as características granulométricas, influência da maré, condições redox das águas de fundo bem como, as ações antrópicas reveladas pelos dados quantitativos e qualitativos. Uma influência sazonal mínima foi observada. No caso da plataforma sudeste, altos valores de matéria orgânica foram observados em núcleos ao longo da plataforma, junto às estações externas das radiais de Santos e Ilha Grande mostrando uma diferenciação acompanhada pelas frações de fósforo orgânico e carbono orgânico. Nas demais radiais, altos valores de CaCO3 foram observados nas estações mais externas. Na Baía do Almirantado as frações predominantes foram P mineral, P detrítico, P-ligado à apatita autigênica, sendo que a forma orgânica foi baixa e associada a baixos valores de carbono orgânico. A quantificação e distribuição das espécies de fósforo nos sedimentos constituem importante ferramenta para compreender o ciclo biogeoquímico do fósforo e dos demais nutrientes nos ecossistemas marinhos. / This work aims to study the total and chemical species of phosphorus in the surface sediments associated to the biogeochemical processes in two estuarine systems, the southeastern continental shelf and Antarctic polar region. Bottom water samples were collected in two seasonal periods (summer-winter) in the estuaries under different degrees of environmental anthorpic impacts. The fraction extraction methodology (SEDEX) applied to obtain the chemical phosphorus species was tested in relation to the certified standards before analyses. The results were reproductive and the extraction efficiency was acceptable. The chemical species concentrations of sedimentary phosphorus in the two estuarine systems showed differences between sectors following the granulometric characteristics, tide influence, redox conditions of the bottom waters as well as anthropic actions revealed by quantitative and qualitative data. A minimum seasonal influence was observed. In the case of eastern continental shelf, high values of organic matter were found in nuclei distribution along the platform in the external stations of Santos and Ilha Grande radials showing a differentiation accompanied by organic phosphorus and C org., fractions. In the other radials high CaCO3 values were observed in the external stations. In the Admiralty Bay the predominant fractions were detrital apatite and authigenic/biogenic apatite, being that organic form was low, linked to low values of organic carbon. The quantification and distribution of P species in the sediments constitute important tools to understand the P and the other nutrient biogeochemical cycles in the sea ecosystems

The aims were to investigate the accuracy of ultrasound in diagnosis of structural fetal anomalies with special focus on false positive findings (I), to evaluate the additional value of second trimester fetal MRI on pregnancy management (II-III) and to estimate the ascertainment in the Swedish Birth Defects Registry and incidence of spina bifida and cleft lip/palate (IV). Retrospectively, 328 fetal autopsies were identified where pregnancies were terminated due to ultrasonographically diagnosed fetal anomalies. In 175 (53.4 %) cases ultrasound and fetal autopsy were identical, in 124 (37.8 %) ultrasound was almost correct, in 23 (7.0 %)  ultrasound diagnoses could not be verified, but fetal autopsy showed other anomalies with at least the same prognostic value and in six (1.8 %)  ultrasound diagnosis could not be verified and autopsy showed no or less severe anomalies (I). Prospectively, 29 pregnancies with CNS- (II) and 63 with non-CNS-anomalies (III) were included. In the CNS study MRI provided no additional information in 18 fetuses (62 %), additional information without changing the management in 8 (28 %) and additional information altering the pregnancy management in 3 (10%). In the non-CNS study the corresponding figures were 43 (68 %), 17 (27 %) and three (5 %), respectively. MRI in the second trimester might be a clinically valuable adjunct to ultrasound for the evaluation of CNS anomalies, especially when the ultrasound is inconclusive due to maternal obesity (II) and in non-CNS anomalies in cases of diaphragmatic hernia or oligohydramnios (III). In newborns, the ascertainments of birth defects are relatively high and assessable, but in pregnancy terminations they are lower or unknown. The incidence of newborns with spina bifida has decreased because of an increased rate of pregnancy terminations (>60%). There is room for improvement concerning the reporting of anomalies from terminated pregnancies (IV).

Este estudo tem como objetivo estudar o fósforo total e as especiações de fósforo nos sedimentos superficiais associados aos processos biogeoquímicos em dois sistemas estuarinos, na plataforma continental sudeste e na região polar antártica. Amostras de água de fundo foram coletadas em dois períodos sazonais (verão-inverno) nos estuários sob diferentes graus de impacto ambiental antrópico. A metodologia de extração das frações de (SEDEX) aplicada para obter as especiações químicas de fósforo foi testada com padrões certificados antes das análises. Os resultados foram reprodutivos e a eficiência da extração foi aceitável. As concentrações das espécies químicas de fósforo sedimentar nos dois estuários mostraram diferenças entre os setores seguindo as características granulométricas, influência da maré, condições redox das águas de fundo bem como, as ações antrópicas reveladas pelos dados quantitativos e qualitativos. Uma influência sazonal mínima foi observada. No caso da plataforma sudeste, altos valores de matéria orgânica foram observados em núcleos ao longo da plataforma, junto às estações externas das radiais de Santos e Ilha Grande mostrando uma diferenciação acompanhada pelas frações de fósforo orgânico e carbono orgânico. Nas demais radiais, altos valores de CaCO3 foram observados nas estações mais externas. Na Baía do Almirantado as frações predominantes foram P mineral, P detrítico, P-ligado à apatita autigênica, sendo que a forma orgânica foi baixa e associada a baixos valores de carbono orgânico. A quantificação e distribuição das espécies de fósforo nos sedimentos constituem importante ferramenta para compreender o ciclo biogeoquímico do fósforo e dos demais nutrientes nos ecossistemas marinhos. / This work aims to study the total and chemical species of phosphorus in the surface sediments associated to the biogeochemical processes in two estuarine systems, the southeastern continental shelf and Antarctic polar region. Bottom water samples were collected in two seasonal periods (summer-winter) in the estuaries under different degrees of environmental anthorpic impacts. The fraction extraction methodology (SEDEX) applied to obtain the chemical phosphorus species was tested in relation to the certified standards before analyses. The results were reproductive and the extraction efficiency was acceptable. The chemical species concentrations of sedimentary phosphorus in the two estuarine systems showed differences between sectors following the granulometric characteristics, tide influence, redox conditions of the bottom waters as well as anthropic actions revealed by quantitative and qualitative data. A minimum seasonal influence was observed. In the case of eastern continental shelf, high values of organic matter were found in nuclei distribution along the platform in the external stations of Santos and Ilha Grande radials showing a differentiation accompanied by organic phosphorus and C org., fractions. In the other radials high CaCO3 values were observed in the external stations. In the Admiralty Bay the predominant fractions were detrital apatite and authigenic/biogenic apatite, being that organic form was low, linked to low values of organic carbon. The quantification and distribution of P species in the sediments constitute important tools to understand the P and the other nutrient biogeochemical cycles in the sea ecosystems

Primäre und sekundäre Lymphome des zentralen Nervensystems (ZNS), PCNSL und SCNSL, sind schwer behandelbar und mit einer ungünstigen Prognose assoziiert. Der ZNS-Tropismus dieser Lymphome hängt mit einer Dysregulation von Genen zusammen, die für Immunabwehr, Chemotaxis, Zellmigration und die Blut-Hirn-Schranke (BBB) relevant sind. Zur Untersuchung der molekularen Mechanismen wurde das Eμ-myc-Mausmodell genutzt, um die Faktoren zu analysieren, die zur ZNS-Tropie beitragen, insbesondere jene, die die BBB destabilisieren und die Immunantwort beeinflussen. Eμ-myc-Lymphome wurden in C57BL/6-Mäuse transplantiert und ZNS-positive von ZNS-negativen Lymphomen histologisch unterschieden. RNA-Sequenzierungen identifizierten Signalwege, die mit dem ZNS-Tropismus korreliert sind. Der NF-κB-Signalweg zeigte hierbei besondere Relevanz: Seine Hemmung in ZNS-positiven Lymphomen verringerte die ZNS-Tropie und stabilisierte die BBB durch den Erhalt der Tight-Junction-Proteine. Zudem ergab sich eine Hochregulation von Gfrα-1 in ZNS-positiven Lymphomen, was eine verstärkte Zellmigration zu hirn-konditioniertem Medium bewirkte. Durch die Aktivierung von Astrozyten und GDNF-Hochregulation wurde die BBB zusätzlich destabilisiert. ZNS-trope Lymphome induzierten Immunmodulationen benachbarter Zellen, wie Mikroglia und Astrozyten, und verstärkten den ZNS-Tropismus durch post-seneszente Signaturen. Das Zusammenspiel zwischen Lymphomzellen und Astrozyten, die Aktivierung der GDNF/Gfrα-1/RET-Signalachse und die BBB-Störung gelten als zentrale Mechanismen der ZNS-Tropie bei DLBCL-ähnlichen Lymphomen. Die gezielte Modulation dieser molekularen Pfade könnte die ZNS-Beteiligung bei aggressiven B-Zell-Lymphomen reduzieren. Weitere Untersuchungen könnten therapeutische Ansätze zur Minderung der ZNS-Tropie und Verbesserung der klinischen Ergebnisse bieten. / Primary and secondary CNS lymphomas (PCNSL and SCNSL) are difficult to treat, with a poor prognosis. CNS tropism in these lymphomas involves immune evasion, chemotaxis, cell migration, and blood-brain barrier (BBB) integrity. This study aimed to identify factors behind CNS tropism using the Eμ-myc mouse lymphoma model to compare CNS-tropic and non-tropic lymphomas. Methods: Eμ-myc lymphomas were transplanted into immunocompetent mice, classified as CNS (+) or CNS (-) by histology. RNA sequencing identified pathways linked to CNS tropism, focusing on NF-κB, which was suppressed using IκBα∆N in CNS (+) lymphomas in vitro and in vivo. BBB disruption was assessed through astrocyte activation and ZO-1 degradation, while BBB permeability was evaluated with the Evans Blue assay. Lymphoma migration towards GDNF-conditioned medium was tested via Boyden chambers, with GDNF/Gfrα-1/RET pathway involvement assessed by knockdown and RET inhibition. Immune modulation was analyzed by PD-L1 expression in astrocytes and microglia co-cultured with CNS lymphomas. Results: RNA sequencing showed upregulation of NF-κB targets, pro-inflammatory cytokines, and SASP in CNS (+) lymphomas. NF-κB inhibition prevented CNS tropism and preserved BBB integrity by blocking ZO-1 degradation. CNS (+) lymphomas displayed Gfrα-1 upregulation and migration toward brain-conditioned medium. Astrocyte activation and GDNF upregulation by CNS (+) lymphomas further impaired BBB stability. CNS (+) lymphomas induced immune modulation in neighboring astrocytes and microglia, with a post-senescence signature linked to CNS tropism. Interactions between lymphoma cells, astrocytes, the GDNF/Gfrα-1/RET axis, and BBB disruption are key to CNS tropism in DLBCL-like lymphomas. Targeting these pathways may help prevent CNS involvement in aggressive B-cell lymphomas, offering potential therapeutic avenues to improve patient outcomes.

Stem cells are endowed with unique qualities: they can both self-renew and give rise to new mature cell types. Central nervous system (CNS) stem cells can give rise to neurons and glia. What factors regulate stem cell fate decisions? Identifying signals that are involved in the regulation of CNS stem cell proliferation, survival, differentiation and migration is fundamental to the understanding of CNS development. In addition, this knowledge hopefully will contribute to more efficient therapies of CNS damages and diseases. The focus of this thesis was to investigate mechanisms of CNS stem cell proliferation and differentiation. We have studied the role for platelet-derived growth factor (PDGF) in these cellular events both in vitro and in vivo. Previous reports have shown that PDGF are implicated in brain tumorigenesis and also supports neuronal differentiation of CNS stem cells. We have found that PDGF promotes survival and proliferation of immature neurons, thereby supporting neuronal differentiation. The intracellular Ras/ERK signaling pathway probably mediates the mitogenic activity of PDGF. In contrast, neuronal differentiation is not dependent on the Ras/ERK pathway. A genetic expression profile of stem cells during their differentiation was obtained. This microarray analysis suggests that PDGF-treated stem cells are at an intermediate stage between proliferation and differentiation. Furthermore, we generated transgenic mice that overexpress Pdgf-b in neural stem cells. Preliminary data indicate no signs of enhanced proliferation of immature neurons. Instead, increased apoptosis was detected in the developing striatum. The results presented in this thesis show how CNS stem cells are regulated by PDGF. PDGFs are widely expressed in the developing CNS and also in some brain tumors, which are thought to arise from CNS stem cells. Thus, this knowledge may contribute to an increased understanding of brain tumorigenesis in addition to normal CNS development.

Endogenous bioelectric fields guide morphogenesis during embryonic development and regeneration by directly regulating the cellular functions responsible for these phenomena. Although this role has been extensively explored in many peripheral tissues, the ability of electric fields to regulate wound repair and stimulate regeneration in the mammalian central nervous system (CNS) has not been convincingly established. This dissertation explores the role of electric fields in regulating the injury response and controlling the regenerative potential of the mammalian CNS. We place particular emphasis on their influence on astrocytes, as specific differences in their injury-induced behaviors have been associated with differences in the regenerative potential demonstrated between mammalian and non-mammalian vertebrates. For example, astrocytes in both mammalian and non- mammalian vertebrates begin migrating towards the lesion within hours and begin to proliferate after an initial delay of two days; subsequently, astrocytes in non-mammalian vertebrates support neurogenesis and assume a bipolar radial glia-like morphology that guides regenerating axons, whereas astrocytes in mammals do not demonstrate robust neurogenesis and undergo a hypertrophic response that inhibits axon sprouting. To test whether injury-induced electric fields drive the astrocytic response to injury, we exposed separate populations of purified astrocytes from the rat cortex and cerebellum to electric field intensities associated with intact and injured mammalian tissues, as well as to those electric field intensities measured in regenerating non-mammalian vertebrate tissues. Upon exposure to electric field intensities associated with uninjured tissue, astrocytes showed little change in their cellular behavior. However, cortical astrocytes responded to electric field intensities associated with injured mammalian tissues by demonstrating dramatic increases in migration and proliferation, behaviors that are associated with their formation of a glial scar in vivo; in contrast, cerebellar astrocytes, which do not organize into a demarcated glial scar, did not respond to these electric fields. At electric field intensities associated with regenerating tissues, both cerebellar and cortical astrocytes demonstrated robust and sustained responses that included morphological changes consistent with a regenerative phenotype. These results support the hypothesis that physiologic electric fields drive the astrocytic response to injury, and that elevated electric fields may induce a more regenerative response among mammalian astrocytes.

Toxocara canis is endoparasitic geohelminth of canids. In its life cycle it uses paratenic host (even humans) and can cause severe problems called cerebral toxocariasis when attacks central nervous system. The exact mechanism of pathogenicity in nervous system is unknown and experimental studies examines rather the acute phase of toxocariasis, therefore we characterized the course of cerebral toxocarosis in mice from acute to chronic phase in this master thesis. We found larvae of the parasite in the brains of mice. The larvae in the tissues occurred both, individually and in clusters. The presence of larvae was observed in regions that affect both movement and memory. We did not find any visible injury nor inflammation surrounding the larvae in the tissue. However, histological examination showed brain tissue pathologies in all mice, namely local necrosis, hemorrhages, thickened vessel walls, cell infiltrates in tissue and around vessels and abnormal angiogenesis. The mice showed neurological symptoms with increasing frequency from the 9th week post infection. Production of specific antibodies was also monitored. The level of antibodies in reinfected mice was higher compared to antibody levels of mice with a single infection. No correlation with the presence of neurological symptoms was shown. Key...

World-wide concerns about human impact on the environment have led to the in 2015 formalizedParis Agreement and the global Sustainable Development Goals. All generations are needed toachieve these targets. Thus, young people need to receive appropriate, sustainability-focusededucation. Even though higher education institutions respond to this demand, students still lackmotivation for sustainable actions. To increase knowledge about this issue, I investigatedmotivation for pro-environmental behaviour in combination with nature-connectedness - a factorthat has not yet been linked with it. In a sample of 208 students, I analysed the correlationsbetween the connectedness to nature scale (CNS) and the motivation toward the environmentscale (MTES). I found correlations, meaning that students who were strongly connected tonature, tend to be more motivated to engage in pro-environmental behaviour as well. However,this does not imply a causal relationship. I also found that students in programs with a main focuson environmental topics scored higher on the CNS and (most categories of) the MTES than otherstudents, and females scored higher than males. Most of the overall mean scores were alignedwith previous research. However, there is still space for improvement and more research needs tobe done. Thus, I recommend future research to use the CNS and MTES in student populations.Moreover, I advise higher education to provide each student with Education for SustainableDevelopment (ESD). It could be beneficial to focus on critical thinking and active, experientiallearning in ESD, possibly with the usage of outdoor education.

Desenvolveram-se métodos bioanalíticos para determinação de anfotericina B e fluconazol em apenas 200 L de plasma e líquor (LCR) através da cromatografia líquida de alta eficiência (CLAE UV-VIS). A anfotericina B foi determinada através de CLAE-VIS utilizando p-nitrofenol como padrão interno, após purificação das matrizes biológicas com acetonitrila, seguida da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por tampão acetato 0,1M pH 5,0 e acetonitrila (50:50,v/v) 0,5mL/min em 385nm; o tempo de corrida foi 15 min. Através da validação o método mostrou-se robusto com 0,2-25,0 µg/mL(linearidade, r2 0,9999), LD 0,1 µg/mL, precisão (5,4% e 6,9%), exatidão expressa através do erro sistemático (3,3% e 2,2%): intra e interdias). Os estudos de estabilidade evidenciaram 1,0% para o erro sistemático e 3% de precisão na bandeja (tempo e condição de análise por 24 h), e os ciclos de congelamento evidenciaram boa estabilidade uma vez que todos os ensaios foram realizados em Laboratório de luz amarela. O fluconazol foi determinado através de CLAE-UV utilizando carbamazepina como padrão interno, após purificação das matrizes biológicas pela extração líquido-líquido com diclorometano em meio alcalino, seguido da análise em coluna Nova Pak C18 (150 x 3,9mm, 4 micron) e fase móvel constituída por água UP e acetonitrila (70:30,v/v) 0,5mL/min em 210nm; o tempo de corrida foi 15 min. O método mostrou-se robusto com 0,2-250 µg/mL(linearidade, r2 0,9998), LD 0,1µg/mL, com boa recuperação absoluta (98%) e relativa (100%), precisão 0,5%/1,3%, exatidão expressa através do erro sistemático (1,2%). Evidenciou-se ótima estabilidade para os extratos em bandeja (tempo e condição de análise por 24 h), na longa duração (20° C, 9 meses) e através dos ciclos de congelamento. Investigaram-se 21 pacientes adultos de ambos os sexos portadores de meningite criptocócica com AIDS após internação emergencial em terapia de alta dose com anfotericina B (1mg/Kg) e fluonazol (400 mg, 12/12 horas) durante 12 semanas. O monitoramento das concentrações de anfotericina B e fluconazol no plasma e no LCR forneceram as razões que permitiram estimar a penetração dos antifúngicos no SNC. Obtiveram-se concentrações de anfotericina B, médias (IC95%): 2,30 (0,02-5,08) µg/mL no plasma e 0,30 (0,19-0,36) µg/mL no LCR. As concentrações do fluconazol, médias (IC95%) foram: 31,7 (20,1-43,3) µg/mL no plasma e 19,4 (11,1-27,7) µg/mL no LCR. Com base nos resultados obtidos conclui-se que a penetração da anfotericina B foi insuficiente (10-27%), enquanto que a do fluconazol mostrou-se adequada com valores médios (IC95%) de 67 (47-87) %. / Analytical methods were developed to determine amphotericin B and fluconazole in only 200 L of plasma and in cerebrospinal fluid (CSF) by liquid chromatography (HPLC UVVIS). Amphotericin B was determined by HPLC - VIS using p-nitrophenol as internal standard, after the purification of biological matrices using acetonitrile, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of acetate buffer 0.1M pH 5.0 plus acetonitrile (50:50,v/v) 0.5mL/min at 385nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-25,0µg/mL (linearity, r2 0.9999), DL 0.1µg/mL, precision (5.4%/6.0%), accuracy expressed as systematic error (3.3%/2.2%). The stability was investigated, error systematic was 1% for the vials on the rack (time and conditions of drug analysis, 24h). Thawing cycles showed good stability after three freezing-thawing cycles. All procedures were performed under yellow light at room temperature. Fluconazole was determined by HPLC - UV using carbamazepine as internal standard, after the purification of biological matrices using liquid-liquid extraction in alkaline medium, followed by chromatographic analysis in a Nova Pak C18 column (150 x 3.9mm, 4 micron) and mobile phase consisting of purified water plus acetonitrile (70:30,v/v) 0.5mL/min at 210nm; the run time required was 15 min. Bioanalytical method validated showed robustness, 0.2-250 µg/mL(linearity, r2 0.9998), DL 0.1µg/mL. Absolute recovery was 98% and relative recovery was 100%, intra/interday precision were 0,5/-1,3%; accuracy expressed as systematic error were 1.2%/1.2%.and relative recovery was 100%. Good stability for the vials on the rack (time and conditions of drug analysis, 24h) and long term stability (at 20o C for 9 months) were demonstrated. Also thawing cycles showed good stability after three freezing-thawing cycles. Twenty one adult patients of both sex were investigated. Inpatients with meningitis by Cryptococcus neoformans with AIDS were under high dose therapy with amphotericin B 1mg/Kg plus fluonazole 400 mg, every 12h during 12 weeks. Therapeutic monitoring of amphotericin B and fluconazole in plasma and in CSF showed ratios that indicate the penetration of antifungal drugs into CNS. Mean (CI95%) data were for amphotericin B 2.30 (0.02-5.08 ) µg/mL in plasma and 0.30 (0.19-0.36) µg/mL in CSF. Fluconazole showed 31.7 (20.1-43.3) µg/mL in plasma and 19.4 (11.1-27.7) µg/mL in CSF. Based on data obtained we conclude that the penetration of amphotericin B was poor (10-27%) while fluconazole was adequate 67% (47-87%), mean (CI95%).

O envelhecimento, processo iminente a todo ser vivo, no SNC é caracterizado por alterações como, por exemplo, a neuroinflamação crônica, que estão associadas a processos de neurodegeneração e ao aumento da incidência de doenças neurológicas ligadas ao surgimento de demência. A insulina, o hormônio anabólico mais importante descoberto até hoje, tem sua sinalização como processo vital que está presente desde bactérias até a espécie humana e desde os tecidos periféricos até o SNC. Mesmo a sinalização cerebral de insulina sendo um tema bem definido na literatura, pouco se sabe sobre a sua função em células da glia, principalmente astrócitos e microglia, componentes chaves do processo de neuroinflamação. A neuroinflamação foi considerada, por muitos anos, tóxica ao SNC, mas atualmente evidências importantes têm sido encontradas sugerindo que processos pró-inflamatórios são primariamente benéficos ao cérebro ou encéfalo e podem assumir papel tóxico à medida que se tornam crônico. Assim, considerando o papel da insulina no SNC, bem como o aumento da expectativa de vida da população mundial que acarreta o aumento dramático da incidência de doenças neurodegenerativas, foi investigada, na presente tese a relação da sinalização fisiológica de insulina com processos cognitivos, neurotróficos e neuroinflamatórios e também a resistência na sinalização da mesma causada pelo envelhecimento cerebral. Foi demonstrado que a administração intracerebroventricular de insulina melhora a cognição de animais jovens, mas o mesmo não ocorre no envelhecimento. A nível celular e molecular, foi visto um distúrbio na conexão da sinalização de insulina e BDNF, bem como na ativação microglial e sinalização pró-inflamatória da insulina que parecem estar comprometidos no envelhecimento. Além disso, foi observado que a microglia é sensível à sinalização direta de insulina via PI3K e que essa sinalização microglial é adaptada e sofre mudanças na vida adulta. Em conjunto com a literatura, foi demostrado por esta tese que existe uma ruptura de paradigmas na interpretação dos processos neuroinflamatórios, que deixam de ser vistos somente como um fator tóxico ao cérebro, mas também como um artifício elementar de adaptação do SNC aos diversos estímulos que as células nervosas recebem durante o curso da vida, desde o nascimento até o envelhecimento. / Aging is a process that is found in all living being in the CNS. It is characterized by modifications, such as chronic neuroinflammation, which are associated with neurodegeneration and represent a risk factor for neurological diseases. Insulin is the most important anabolic hormone ever discovered. Insulin signaling represents an essential process that is present from bacteria to humans and from the periphery to the brain. Insulin signaling in the CNS is a well-defined topic in the literature. Most of the knowledge regarding brain insulin signaling still report findings in neurons and little is known about insulin function in glia, especially astrocytes and microglia that are key players of neuroinflammation. Neuroinflammation has been considered a toxic factor to the CNS, however, in the last few years, important evidences have been found that proinflammatory processes are primarily beneficial and may play a toxic role as soon as they become chronic. Thus, considering the role of insulin in the CNS, as well as the increased populational life spam worldwide, the present thesis investigated the relation of physiological insulin signaling and the brain insulin signaling caused by aging in cognition, neurochemistry and neuroinflammation. We showed that insulin intracerebroventricular administration improved the cognition of young animals, but the same was not observed in aging. At the cellular and molecular level, we found a disruption in the connection of insulin and BDNF signaling. We also show that a microglial activation and pro-inflammation triggered by insulin in young brain appear to be lost during aging. In addition, it was observed that microglia is sensitive to direct insulin signaling via PI3K and that this microglial signaling suffers adaptations and changes during life. Together with the recently changes in the literature, the findings of this work demonstrate that there is a rupture of paradigms in the interpretation of neuroinflammatory processes, which are no longer seen only as a toxic factor to the brain, but also as an smart adaptation of the CNS to the various stimuli that brain cells receive during the course of life, from birth to aging.