Doença de Chron pediátrica : influência da nutrição entérica na microbiota

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016A Doença Inflamatória Intestinal é um conjunto de doenças inflamatórias intestinais crónicas imuno-mediadas: a Colite Ulcerosa, a Doença de Crohn e a Colite Indeterminada. A Doença de Crohn distingue-se da Colite Ulcerosa e da Colite Indeterminada por afectar todo o tracto gastrointestinal. Embora a Doença de Crohn se possa desenvolver em todas as idades, tem existido um aumento significativo da sua prevalência em idade pediátrica pelo que o estudo desta doença se torna de particular interesse, principalmente na procura de explicações etiológicas e desenvolvimento de alvos terapêuticos que contribuam para o normal desenvolvimento da criança afectada. A Microbiota gastrointestinal tem um papel preponderante na homeostasia do indivíduo e a Disbiose existente na Doença de Cronh pode ser um dos factores etiológico da doença. A Nutrição Entérica como processo terapêutico procura promover a remissão da actividade da doença, melhorar o estado nutricional da criança e o seu potencial de crescimento e desenvolvimento pubertário. Com este trabalho pretendeu-se estabelecer o panorama científico actual sobre a relação entre a Disbiose existente, e qual a influência da terapêutica com a Nutrição Entérica na promoção de uma Microbiota o mais aproximado possível do padrão de microrganismos comensais.Inflamatory Bowel Disease is a group of immune-mediated chronic intestinal diseases with three major subtypes: Ulcerative Colitis, Crohn’s Disease and Unclassified Colitis. Crohn’s Disease differs from the other two by affecting all the gastrointestinal tract. It can develop in all ages, but there has been a rising prevalence of paediatric onset of Crohn’s Disease. For the appropriate development of these children the growing necessity of potential new explanations for the aetiology and new treatment options are required. The gastrointestinal Microbiota is needed for important functions that comprise the human homeostasis but its dysbiosis in Crohn’s Disease can stand for a possible pathogenesis factor. The Enteric Nutrition induces remission and helps mitigate the nutritional consequences these children suffer. We aimed to establish the current scientific consensus about the enteric nutrition and its influence in the Microbiota of paediatric Crohn’s Disease

Novel players in the aging synapse: impact on cognition

© Mariana Temido-Ferreira, et al. 2019; Published by Mary Ann Liebert, Inc. This Open Access article is distributed under the terms of the Creative Commons Attribution Noncommercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are cited.While neuronal loss has long been considered as the main contributor to age-related cognitive decline, these alterations are currently attributed to gradual synaptic dysfunction driven by calcium dyshomeostasis and alterations in ionotropic/metabotropic receptors. Given the key role of the hippocampus in encoding, storage, and retrieval of memory, the morpho- and electrophysiological alterations that occur in the major synapse of this network-the glutamatergic-deserve special attention. We guide you through the hippocampal anatomy, circuitry, and function in physiological context and focus on alterations in neuronal morphology, calcium dynamics, and plasticity induced by aging and Alzheimer's disease (AD). We provide state-of-the art knowledge on glutamatergic transmission and discuss implications of these novel players for intervention. A link between regular consumption of caffeine-an adenosine receptor blocker-to decreased risk of AD in humans is well established, while the mechanisms responsible have only now been uncovered. We review compelling evidence from humans and animal models that implicate adenosine A2A receptors (A2AR) upsurge as a crucial mediator of age-related synaptic dysfunction. The relevance of this mechanism in patients was very recently demonstrated in the form of a significant association of the A2AR-encoding gene with hippocampal volume (synaptic loss) in mild cognitive impairment and AD. Novel pathways implicate A2AR in the control of mGluR5-dependent NMDAR activation and subsequent Ca2+ dysfunction upon aging. The nature of this receptor makes it particularly suited for long-term therapies, as an alternative for regulating aberrant mGluR5/NMDAR signaling in aging and disease, without disrupting their crucial constitutive activity.M.T.-F. and J.E.C. were supported by a fellowship from Fundação para a Ciência e Tecnologia (FCT, Portugal); L.V.L is an Investigator CEEC-FCT. P.A.P. is supported by EU Joint Program—Neurodegenerative Disease Research (JPND) project CIRCPROT (jointly funded by BMBF, MIUR, and EU Horizon 2020 grant agreement no. 643417). This study was also funded by Santa Casa da Misericórdia - Mantero Belard 2018 (MB-7-2018) and by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado.info:eu-repo/semantics/publishedVersio

A eta-alpha and A eta-beta peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

Background: Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods: With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results: We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions: These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes

Anti-Inflammatory Treatment with FTY720 Starting after Onset of Symptoms Reverses Synaptic Deficits in an AD Mouse Model

Therapeutic approaches providing effective medication for Alzheimer’s disease (AD) patients after disease onset are urgently needed. Previous studies in AD mouse models suggested that physical exercise or changed lifestyle can delay AD-related synaptic and memory dysfunctions when treatment started in juvenile animals long before onset of disease symptoms, while a pharmacological treatment that can reverse synaptic and memory deficits in AD mice was thus far not identified. Repurposing food and drug administration (FDA)-approved drugs for treatment of AD is a promising way to reduce the time to bring such medication into clinical practice. The sphingosine-1 phosphate analog fingolimod (FTY720) was approved recently for treatment of multiple sclerosis patients. Here, we addressed whether fingolimod rescues AD-related synaptic deficits and memory dysfunction in an amyloid precursor protein/presenilin-1 (APP/PS1) AD mouse model when medication starts after onset of symptoms (at five months). Male mice received intraperitoneal injections of fingolimod for one to two months starting at five to six months. This treatment rescued spine density as well as long-term potentiation in hippocampal cornu ammonis-1 (CA1) pyramidal neurons, that were both impaired in untreated APP/PS1 animals at six to seven months of age. Immunohistochemical analysis with markers of microgliosis (ionized calcium-binding adapter molecule 1; Iba1) and astrogliosis (glial fibrillary acid protein; GFAP) revealed that our fingolimod treatment regime strongly down regulated neuroinflammation in the hippocampus and neocortex of this AD model. These effects were accompanied by a moderate reduction of Aβ accumulation in hippocampus and neocortex. Our results suggest that fingolimod, when applied after onset of disease symptoms in an APP/PS1 mouse model, rescues synaptic pathology that is believed to underlie memory deficits in AD mice, and that this beneficial effect is mediated via anti-neuroinflammatory actions of the drug on microglia and astrocytes

IL-17 triggers the onset of cognitive and synaptic deficits in early stages of Alzheimer’s disease

© 2021 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Neuroinflammation in patients with Alzheimer's disease (AD) and related mouse models has been recognized for decades, but the contribution of the recently described meningeal immune population to AD pathogenesis remains to be addressed. Here, using the 3xTg-AD model, we report an accumulation of interleukin-17 (IL-17)-producing cells, mostly γδ T cells, in the brain and the meninges of female, but not male, mice, concomitant with the onset of cognitive decline. Critically, IL-17 neutralization into the ventricles is sufficient to prevent short-term memory and synaptic plasticity deficits at early stages of disease. These effects precede blood-brain barrier disruption and amyloid-beta or tau pathology, implying an early involvement of IL-17 in AD pathology. When IL-17 is neutralized at later stages of disease, the onset of short-memory deficits and amyloidosis-related splenomegaly is delayed. Altogether, our data support the idea that cognition relies on a finely regulated balance of "inflammatory" cytokines derived from the meningeal immune system.This work was funded by the Fundação para a Ciência e Tecnologia (IF/00013/2014, LISBOA-01-0145-FEDER-028241, and PTDC/MED-IMU/1988/2020) to J.C.R., Santa Casa da Misericórdia (MB-7-2018) and Fundacão para a Ciência e Tecnologia (PTDC/BIM-MEC/4778/2014 and IF/00105/2012) to L.V.L., and PD/BD/114103/2015 to H.C.B. The ORCIDs for this article are as follows: 0000-0001-8367-3005 (L.V.L.) and 0000-0002-7852-343X (J.C.R.).info:eu-repo/semantics/publishedVersio

Age-related shift in LTD is dependent on neuronal adenosine A(2A) receptors interplay with mGluR5 and NMDA receptors

Synaptic dysfunction plays a central role in Alzheimer's disease (AD), since it drives the cognitive decline. An association between a polymorphism of the adenosine A2A receptor (A2AR) encoding gene-ADORA2A, and hippocampal volume in AD patients was recently described. In this study, we explore the synaptic function of A2AR in age-related conditions. We report, for the first time, a significant overexpression of A2AR in hippocampal neurons of aged humans, which is aggravated in AD patients. A similar profile of A2AR overexpression in rats was sufficient to drive age-like memory impairments in young animals and to uncover a hippocampal LTD-to-LTP shift. This was accompanied by increased NMDA receptor gating, dependent on mGluR5 and linked to enhanced Ca(2+) influx. We confirmed the same plasticity shift in memory-impaired aged rats and APP/PS1 mice modeling AD, which was rescued upon A2AR blockade. This A2AR/mGluR5/NMDAR interaction might prove a suitable alternative for regulating aberrant mGluR5/NMDAR signaling in AD without disrupting their constitutive activity

Adenosine A2A receptors modulate BDNF both in normal conditions and in experimental models of Huntington’s disease

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, enhances synaptic transmission and regulates neuronal proliferation and survival. Functional interactions between adenosine A2A receptors (A2ARs) and BDNF have been recently reported. In this article, we report some recent findings from our group showing that A2ARs regulate both BDNF functions and levels in the brain. Whereas BDNF (10 ng/ml) increased the slope of excitatory postsynaptic field potentials (fEPSPs) in hippocampal slices from wild-type (WT) mice, it was completely ineffective in slices taken from A2AR knock-out (KO) mice. Furthermore, enzyme immunoassay studies showed a significant reduction in hippocampal BDNF levels in A2AR KO vs. WT mice. Having found an even marked reduction in the striatum of A2AR KO mice, and as both BDNF and A2ARs have been implicated in the pathogenesis of Huntington’s disease (HD), an inherited striatal neurodegenerative disease, we then evaluated whether the pharmacological blockade of A2ARs could influence striatal levels of BDNF in an experimental model of HD-like striatal degeneration (quinolinic acid-lesioned rats) and in a transgenic mice model of HD (R6/2 mice). In both QA-lesioned rats and early symptomatic R6/2 mice (8 weeks), the systemic administration of the A2AR antagonist SCH58261 significantly reduced striatal BDNF levels. These results indicate that the presence and the tonic activation of A2ARs are necessary to allow BDNF-induced potentiation of synaptic transmission and to sustain a normal BDNF tone. The possible functional consequences of reducing striatal BDNF levels in HD models need further investigation

The role of adenosine A2A receptors on neuromuscular transmission upon ageing

Tese de doutoramento, Ciências Biomédicas (Neurociências), Universidade de Lisboa, Faculdade de Medicina, 2012Adenosine is a neuromodulator with important actions in the nervous system. The activation of adenosine A2A receptors has been shown to modulate the action of other receptors. Considering that it was observed an interaction between adenosine A2A receptors and TrkB receptors in hippocampus, I hypothesized that the activation of A2A receptors could also facilitate BDNF actions on neuromuscular transmission. To answer that question I performed intracellular electrophysiological recordings in isolated preparations of the phrenic-nerve diaphragm from male infant rats. The data herein described clearly shows that there is a crosstalk between A2A receptors and TrkB receptors at the neuromuscular junction, where A2A receptors trigger the excitatory action of BDNF on neuromuscular transmission, through a mechanism that involves PLCy. When I was investigating the interaction between adenosine A2A receptors and TrkB receptors on neuromuscular transmission, I induced the increase of the endogenous adenosine level at the synaptic cleft, with an adenosine kinase inhibitor, 5`-iodotubericidin (ITU). It was observed that instead of inhibition, ITU greatly facilitated neuromuscular transmission. It was the first time that an excitatory effect induced by endogenous adenosine, at low frequency stimulation, was observed. Therefore I considered of interest to study the balance between adenosine A1 and A2A receptors at the neuromuscular junction upon ageing, since the activation of adenosine A2A receptors has been shown to influence the actions of adenosine A1 receptors and no one had looked at the excitatory actions of adenosine in aged rats at the neuromuscular junction. I performed intracellular electrophysiological experiments in isolated preparations of the phrenic-nerve diaphragm from four groups of male rats, with different ages: infant (3-4 weeks old), young adult (12-16 weeks old), older adult (36-40 weeks old) and aged (70-80 weeks old). The data herein reported clearly showed that there is a predominance of excitatory adenosine effects at the motor nerve endings of infant rats. Moreover, ageing influenced adenosine A1 and A2A receptors, at the motor nerve terminals, in a different manner. The actions of A2A receptors decreased with ageing, even disappearing in aged rats, whereas the actions of A1 receptors remained unchanged upon ageing. Furthermore, the actions of adenosine A2A receptors on neuromuscular transmission are dependent on adenosine A1 receptors activation, since the excitatory effect of A2A receptors was prevented by the adenosine A1 receptor antagonist. In conclusion, the data presented here demonstrate that adenosine A2A receptors play a crucial role at the neuromuscular junction, since their effects on neuromuscular transmission predominate over adenosine A1 receptors, in infant rats, and the excitatory effect of BDNF on neuromuscular transmission is dependent on their activation. The absence of adenosine A2A receptors effects in aged rats might be one of the causes of the neuromuscular transmission impairment. The results herein described are relevant for a better understanding on the role of adenosine at the neuromuscular junction upon ageing, opening novel scientific questions such as investigate the role of adenosine A2A receptors on neuromuscular transmission in the cenarios of neuromuscular disease as, for example, the amyotrophic lateral sclerosis disease.A adenosina é um importante neuromodulador do sistema nervoso. As suas acções estão dependentes da activação de receptores metabotrópicos associados às proteínas G. Os receptores A2A e os receptores A1 são considerados os receptores de alta afinidade para o ligando adenosina. A activação destes receptores desencadeia reacções intracelulares de natureza oposta. A activação dos receptores A2A da adenosina, por estarem associados a uma proteína G excitatória causa o aumento da concentração de uma molecula intracellular que desempenha a função de segundo mensageiro, o monofosfato de adenosina (AMP) cíclico. Pelo contrário, a activação dos receptores A1 da adenosina, que estão associados a uma proteína G inibitória, desencadeia a diminuição da referida molécula. Nos últimos anos tem sido demonstrado que os receptores A2A da adenosina, além de exercerem efeitos directos na libertação de diferentes neurotransmissores, também modulam as acções de outros receptores, como por exemplo os receptores inibitórios A1 da adenosina e os receptores do factor neurotrófico derivado do cérebro (BDNF, do inglês brain-derived neurotrophic factor), os receptores TrkB. O objectivo do trabalho descrito nesta tese foi perceber o papel dos receptores A2A na modulação da transmissão sináptica na junção neuromuscular de diafragma de rato ao longo da idade (desde os juvenis até aos animais próximo do termo de vida), bem como investigar a interacção destes receptores com os receptores TrkB do BDNF e com os receptores A1 da adenosina. Utilizou-se uma abordagem funcional em que que se avaliou a transmissão neuromuscular evocada e espontanea, por métodos electrofisiológicos, em 4 grupos de animais com idades diferentes: juvenis (3- 4 semanas), jovens adultos (12-16 semanas), adultos de meia idade (36-40 semanas) e velhos (70-80 semanas). Tendo em conta que no hipocampo de rato as acções do BDNF são dependentes da activação dos receptores A2A da adenosina considerou-se importante avaliar se a interacção entre os receptores A2A e as acções do BDNF, observada no hipocampo de rato, se observa também ao nível da junção neuromuscular. Os resultados obtidos e descritos nesta dissertação mostram que o efeito excitatório do BDNF na junção neuromuscular depende da activação dos receptores A2A da adenosina. Mais, os resultados descritos nesta tese demonstram, pela primeira vez, que a interacção entre os receptores A2A e TrkB, na junção neuromuscular, se verifica através da activação da via de transdução da cinase de proteína do tipo A pelos receptores A2A, a qual permite a acção do BDNF, via receptores TrkB acoplados à lipase fosfatada do tipo C gamma, promovendo, desse modo, o aumento da transmissão neuromuscular. Quando estávamos a avaliar se a activação dos receptores A2A poderia facilitar o efeito do BDNF na transmissão neuromuscular, utilizámos uma ferramenta famacológica para promover o aumento dos níveis de adenosina endógena na fenda sináptica, isto é, adicionámos um inibidor da cinase de adenosina, iodotubericidina (ITU), ao banho de perfusão. A ITU impede a metabolização da adenosina intracelular em monofosfato de adenosina. O aumento da concentração de adenosina intracellular causa a sua libertação para a fenda sináptica através do transportador equilibrativo de nucleósidos. De modo inesperado a ITU, em vez de inibir, potenciou a transmissão neuromuscular de modo significativo. Este foi um resultado original, na medida em que nenhum autor, até agora, que seja do meu conhecimento, tinha descrito um efeito excitatório da adenosina endogena via receptores A2A, com um protocolo de estimulação de baixa frequência (0,5 Hz). Considerou-se, desse modo, importante investigar o equilibrio existente entre os receptores da adenosina A1 e A2A. Foi realizado um estudo farmacológico com o objectivo de investigar quais as condições que determinam a activação dos receptores A1 ou dos receptores A2A da adenosina. Os resultados que a seguir descrevemos documentam de modo claro que ambos os receptores de adenosina, A1 e A2A, presentes na junção neuromuscular de ratos jovens, podem ser activados por baixas concentrações de adenosina extracelular; no entanto a activação dos receptores A2A predomina. A maior parte das doenças neurodegenerativas tem incidência na velhice, no entanto existem poucos estudos em animais velhos ou muito velhos. Os receptores da adenosina têm assumido um papel cada vez mais relevante como alvo terapêutico para algumas doenças neurodegenerativas. Os poucos estudos que existem sobre o papel da adenosina na modulação da transmissão sináptica em animais envelhecidos foram realizados no sistema nervoso central. Por esse motivo considerámos importante investigar se o predomínio das acções excitatórias dos receptores A2A sobre os receptores A1, observado nos ratos juvenis, se mantem ao longo da idade. Este estudo permitiu obter um conjunto de dados que possibilitam caracterizar a fisiologia da transmissão neuromuscular ao longo da vida. Observámos que a transmissão sináptica, ao nível da junção neuromuscular de diafragma de rato, se mantém inalterada ao longo da vida, ficando comprometida apenas na velhice. Os animais muito velhos apresentam a amplitude e o conteúdo quântico dos potenciais evocados de placa motora, bem como a frequência dos potenciais miniatura de placa motora significativamente diminuídos. Em relação ao efeito da idade nos receptores de adenosina, os resultados apresentados demonstram que a idade influencia os receptores de adenosina A1 e A2A de modo diferente. A amplitude dos efeitos excitatórios causados pela adenosina libertada endogenamente ou por um agonista inespecífico A1/A2A tendem a diminuir ao longo da vida, desaparecendo nos animais muito velhos, altura em que apenas a inibição medidada pela activação dos receptores A1 é observada. Em conclusão, os resultados obtidos neste trabalho demonstram que os receptores A2A de adenosina têm um papel crucial na manutenção da transmissão neuromuscular, uma vez que as suas acções predominam sobre as dos receptores A1 e as acções do BDNF dependem da sua activação. A ausência de efeitos excitatórios dos receptores A2A nos animais muito velhos pode constituir uma das causas para o comprometimento da transmissão neuromuscular observada nessa idade. Os resultados que se descrevem na presente dissertação são relevantes para uma melhor compreensão do papel da adenosina na junção neuromuscular ao longo do envelhecimento, abrindo novas questões científicas, tais como investigar o papel dos receptores A2A da adenosina na transmissão neuromuscular em situação de doença neuromuscular, por exemplo na esclerose lateral amiotrófica

A Tripanossomose (T. Cruzi) em indivíduos infetados com HIV: influência da patogénese na clínica, imunologia, tratamento e prevenção

Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2016A tripanossomose é uma infeção causada por um parasita flagelado intracelular Trypanossoma Cruzi (T. Cruzi), que origina a Doença de Chagas. O parasita infecta vetores vertebrados, os triatomíneos, que por picada infetam os mamíferos. Segundo dados da Organização Mundial de Saúde, atualizados em Março, estima-se que existam 6 a 7 milhões de pessoas infetadas a nível mundial. É endémica da América Latina e constituída por duas fases: uma aguda e uma crónica. A aguda caracteriza-se pela presença de um chagoma ou sinal de Romanã, febre, cafaleias, diarreia - mononucleose-like. Cerca de 30% dos casos entram na fase crónica onde a mesma adquire formas mais graves: problemas cardíacos, digestivos ou os dois em simultâneo. Em casos mais extremos, concomitantes com imunodepressão do sistema imunitário, podem ocorrer danos no Sistema Nervoso Central (SNC). O Vírus da Imunodeficiência Humana (HIV) é o responsável pelo Síndrome da Imunodeficiência Adquirida (SIDA), existindo um total de 36.7 milhões de pessoas infetadas mundialmente. O cenário verificado é um enfraquecimento do sistema imunitário, pela depleção de células T, Natual Killers (NK) e células B. Caracteriza-se por três fases: uma sintomática, onde maioritariamente existe ausência de sintomatologia e nos restantes casos o síndrome retroviral agudo (mialgias, cefaleias, febre, entre outros); outra assintomática e a terceira a fase de SIDA. Nesta as complicações clínicas incluem doença neurocognitiva, doença arterial coronária, complicações infeciosas (por exemplo infeção por T.Cruzi.) ou malignas (como sarcoma de Kaposi). No caso de uma coinfecção HIV/T.Cruzi, a Doença de Chagas comporta-se como uma doença oportunista. Com o deficiente funcionamento do sistema imunitário, verifica-se uma reativação da Doença de Chagas. As manifestações clínicas são graves e passam maioritariamente pelo comprometimento do SNC e cardíaco. Não existem dados objetivos sobre os parâmetros que estão na origem deste recrudescimento, nem tratamento padronizado. Assim, é imperioso promover mais investigação científica nesta área, onde a taxa de mortalidade pode ascender aos 99%, como resultado de meningoencefalites.Trypanosomiasis is an infection caused by an intracellular parasitic flagellate: Trypanosoma cruzi, which causes Chagas' disease. The parasite infects vertebrates vectors, triatomine bugs, which can infect mammals through bite. According to the World Health Organization, data updated in March this year, it is estimated that there are 6 to 7 million people infected worldwide. It is endemic to Latin America and consists of two phases: acute and chronic. The acute phase is characterized by the presence of a chagoma or Roman signal, fever, headache, diarrhea - mononucleose-like. Approximately 30% of patients enter the chronic phase where it acquires the more severe cardiac problems, digestive or both simultaneously. In more extreme cases with concomitant immunosuppression of the immune system, it can cause damage to the CNS. HIV is the virus responsible for AIDS and there are a total of 36,7 million people infected worldwide. The observed scenario is a weakening of the immune system, by depletion of T cells, NK cells and B cells and is characterized by three phases: a symptomatic, where there is mostly no symptoms and in other cases the acute retroviral syndrome (myalgia, headache, fever, among others); a second phase, asymptomatic, and the third one, wich is AIDS. The clinical complications of this latter phase includes neurocognitive disease, coronary artery disease, infectious complications (e.g. infection by T. cruzi.) or malignant (such as Kaposi's sarcoma). In the case of HIV coinfection / Trypanosoma cruzi, Chagas disease behaves as an opportunistic disease. With the malfunction of the immune system, a reactivation of Chagas' disease occurs. The clinical manifestations are severe and characterized by CNS involvement and heart. There are no objective data on the parameters that are at the origin of this resurgence or standard treatment. Thus, it becomes more urgent the scientific research in this area, where the mortality rate can rise to 99%, as a result of meningoencephalitis