Orientador: Ana Elizabete Silva / Coorientador: Sonia Maria Oliani / Banca: Henrique César Santejo Silveira / Banca: Patricia Maluf Cury / Banca: Dorotéia Rossi S. Souza / Banca: Debora Ap. Pires de C. Zuccari / Resumo: Apesar do declínio da incidência, o câncer gástrico ocupa ainda a terceira posição em causa de morte por câncer no mundo, tendo como principal fator de risco a bactéria Helicobacter pylori. Esta bactéria pode levar a uma inflamação persistente através da produção de citocinas pró-inflamatórias e de espécies reativas de oxigênio e nitrogênio, estimulando a proliferação celular bem como outros processos envolvidos na carcinogênese. Ainda envolvidos nestes processos tem sido observada a participação de microRNAs, que exercem papel importante na regulação pós-transcricional, influenciando processos fisiológicos normais da célula bem como aqueles ligados às doenças, como por exemplo o câncer gástrico. Alguns miRNAs podem atuar como oncogenes, genes supressores de tumor e biomarcadores para diversas patologias, podendo alvejar genes relacionados com inflamação e câncer como o gene ANXA1 (Anexina-A1). A Anexina-A1 é uma proteína anti-inflamatória e com ação anti-proliferativa, que se liga à receptores do tipo formil peptídeo como por exemplo FPR1 e FPR2, ambos sabidamente relacionados com a progressão de doenças como o câncer. Desta forma o presente trabalho teve como objetivos avaliar a expressão da proteína Anexina A1 e seus receptores FPR1 e FPR2, bem como avaliar a expressão do RNAm da ANXA1 e de miRNAs que possam modular a expressão desse gene (hsa-mir-27a, hsa-mir-196a e hsa-mir-222) em adenocarcinoma gástrico e correlacionar estes resultados com os aspectos clínico-patológicos. Foram avaliadas 31 amostras de adenocarcinoma gástrico, assim como as regiões metaplásica ou normal adjacentes ao tumor. A quantificação relativa (RQ) do RNAm da ANXA1 e miRNAs foi realizada por PCR quantitativo em tempo real utilizando ensaio TaqMan, e a expressão proteica da AnxA1, FPR1 e FPR2 por imuno-histoquímica e análise densitométrica. Em... / Abstract:Gastric cancer still ranks third in cause of cancer death worldwide, despite the decline in its incidence, being Helicobacter pylori the main risk factor for this disease. This bacterium can lead to persistent inflammation via the production of proinflammatory cytokines and reactive oxygen and nitrogen species, stimulating cell proliferation and other processes involved in carcinogenesis. Still involved in this process, it has been observed the participation of miRNAs, which play an important role in post- transcriptional regulation, influencing normal physiological processes of the cell as well as those linked to diseases such as gastric cancer. Some miRNAs can act as oncogenes, tumor suppressor genes and biomarkers for various diseases, can targetting genes linked to inflammation and cancer such as ANXA1 gene (Annexin A1). Annexin A1 is an anti-inflammatory protein with anti-proliferative action that binds to formyl peptide receptors such as, FPR1 and FPR2, both known to be related to the progression of diseases such as cancer. Thus, the present study aimed to evaluate the expression of Annexin A1, FPR1 and FPR2 receptors, and the expression of mRNA ANXA1 and miRNAs (hsa-mir-27a, hsa-mir-196a and hsa-miR 222) in gastric adenocarcinoma, also correlate these results to the clinicopathological features. 31 adenocarcinoma samples were evaluated, as well as normal or metaplastic region adjacent to the tumor. Relative quantification (RQ) of miRNA and mRNA ANXA1 was evaluated by TaqMan assay and protein expression AnxA1, FPR1 and FPR2 by immunohistochemistry and densitometry analysis. Regarding the relative expression the following results were observed, increased expression in tumors of ANXA1 (RQ = 1.374; p < 0.001) and miR- 196a that showed increased expression it he metaplastic tissue (RQ = 4.784; p = 0.0016) and tumor (RQ = 16.99; p < 0.001) compared to normal tissue. The miR- 27a did not appear differentially expressed in different tissues ... / Doutor

Orientador: Flávia Cristina Rodrigues-Lisoni / Coorientador: Sonia Maria Oliani / Banca: Sandra Helena Poliselli Farsky / Banca: Wilson Araujo da Silva Júnior / Banca: Joice Matos Biselli Périco / Banca: Marilia de Freitas Calmon Saiki / Resumo: O câncer cervical é uma das principais neoplasias ginecológicas em todo o mundo. O microambiente tumoral influencia no processo tumorigênico. Nas diferentes fases da tumorigênese as inflamações crônicas estão envolvidas. Assim, a proteína anti-inflamatória anexina A1 (ANXA1), que é expressa pelas células tumorais, tem sido relacionada ao processo tumorigênico. Diante dessas considerações, o objetivo do presente trabalho foi investigar a ação do peptídeo mimético da proteína ANXA1 em células de carcinoma de colo de útero. As metodologias utilizadas foram Análise de proliferação, migração, viabilidade e apoptose celular, além da modulação da expressão de genes relacionados à inflamação por PCR quantitativa. No primeiro modelo, foi utilizado o Meio Condicionado da linhagem HUVEC (endotélio) (HMC) para realizar o cultivo celular junto as linhagens HaCat (normal) e HeLa (câncer). Nossos resultados mostram que as células de câncer cervical apresentam diminuição da proliferação, enquanto na morfologia, migração, viabilidade e apoptose celular não foram observadas mudanças. A análise dos genes, MMP2 e MMP9 mostrou aumento de expressão, enquanto os genes COX2, EP3 e EP4 diminuição, após estímulo com HMC. No segundo modelo, foi realizada comparação de duas linhagens tumorigênicas (HeLa e SiHa) com a linhagem HaCaT. A ANXA1 aumentou a expressão de EP4 e MMP9 e diminuiu a proliferação celular e a apoptose. Nesse contexto sugerimos que o peptídeo pode modular mecanismos celulares e... / Abstract: Cervical cancer is one of the main gynaecological cancers around the world. The tumor microenvironment influences in the tumor process. In the different tumour phases the chronic inflammations are associated. Thus, the anti-inflammatory protein annexin A1 (ANXA1), which is expressed by tumour cells, has been linked to the tumourigenesis. In view of this, the aim of the present work was to investigate the ANXA1 mimetic peptide action in the uterus carcinoma cells. The methodologies used were cellular proliferation, migration, viability and apoptosis assay, besides the gene expression modulation of genes related to inflammatory pathways by quantitative PCR. In the first model was used the conditioned medium of HUVEC cells (endothelium) (HMC) to performed the co-culture with HaCaT cell line (normal) and HeLa cell line (cancer). Our results showed that the cervical cancer cells had a decrease in proliferation, while changes in cellular morphology, migration, viability and apoptosis were not observed. The analysis of the MMP2 and MMP9 genes showed an upregulation, while the COX2, EP3 and EP4 presented a downregulation, after the HMC stimulus. In the second model was performed a comparison between two tumor cell lines (HeLa and SiHa) with the HaCaT cell line. The ANXA1 upregulated EP4 and MMP9 and decreased the cellular proliferation and apoptosis. That way, we suggest that the peptide may modulate cellular and molecular mechanisms in the cervical carcinogenesis, however its use as a possible therapeutic alternative should be better explored / Doutor

The development of a first myocardial infarction is associated with a large number of contributing factors. Age, male sex, hypertension, smoking, diabetes, body mass index and hypercholesterolemia are considered as established risk factors. The primary aim of the present dissertation was to evaluate whether specific biomarkers could improve the prediction of subjects at risk for a first myocardial infarction when considered in addition to established cardiovascular risk factors. The biomarkers investigated include: tissue plasminogen activator (tPA), plasminogen activator inhibitor-1 (PAI-1), thrombomodulin (TM), von Willebrand factor (VWF), dehydroepiandrosterone sulfate (DHEAS), lipoprotein (a) (Lp(a)), leptin, apolipoproptein A1 (ApoA1), proinsulin, homocysteine and homozygosity for the 5,10- methylenetetrahydrofolate reductase (MTHFR) C&gt;T genotype. A secondary objective was to determine whether a first myocardial infarction leads to increased plasma homocysteine concentrations and whether the association between homocysteine and myocardial infarction was greater at follow-up compared to baseline. The study population consisted of 36 405 subjects screened and included in the Västerbotten Intervention Program and the Northern Sweden MONICA cohorts between January 1, 1985 and September 30, 1994. A nested incident case-referent study design was used. Seventy eight cases with a first myocardial infarction were identified, and from the same cohort twice as many sex and age matched referents were randomly selected. Moreover, a follow-up health survey (average 8.5 years between surveys) was conducted with 50 cases and 56 matched referents. High plasma levels of tPA and PAI-1 mass concentration, VWF, proinsulin, leptin and Lp(a) and low plasma levels of ApoA1 were associated with subsequent development of a first myocardial infarction in univariate conditional logistic regression analysis. For PAI-1 and tPA, this relation was found in both men and women. For tPA, but not for PAI-1 and VWF, this association was independent of established risk factors. In women, high plasma concentrations of TM were associated with significant increases in risk of a first myocardial infarction. No predictive values of DHEAS, homocysteine or for the point mutation C677&gt;T in the gene for MTHFR was found regarding the risk of a first myocardial infarction. The summarised importance of haemostatic and metabolic variables (proinsulin, lipids including Lp(a) and leptin) in predicting first myocardial infarction in men, as well as possible interactions among these variables, were studied. High tPA and Lp(a) and low ApoA1 remained significant risk markers in multivariate analysis independent of established risk factors. There were non-significant synergic interactions between high Lp(a) and leptin and tPA respectively, and between high Lp(a) and low ApoA1. In the follow-up study plasma homocysteine and plasma creatinine increased significantly, and plasma albumin decreased significantly over time. Conditional univariate logistic regression indicated that high homocysteine at follow-up but not at baseline was associated with first myocardial infarction but the relation disappeared in multivariate analyses including plasma creatinine and plasma albumin. High plasma creatinine remained associated with first myocardial infarction at both baseline and follow-up. In conclusion, the present results support the hypothesis that biomarkers, in addition to the traditional cardiovascular risk factors, carry predictive information on the risk of developing a first myocardial infarction.

La synthèse énantiosélective de deux pyrrolizidines naturelles, la (+)-rétronecine et la (+)-hyacinthacine A1, a été effectuée en se basant sur la réaction de cycloaddition [2+2] du dichlorocétène sur un éther d'énol chiral encombré. Ces synthèses sont caractérisées par une séquence très efficace conduisant à un lactame chiral (intermédiaire commun) qui conduit facilement au squelette pyrrolizidine.<br />La synthèse de la (+)-rétronecine est effectuée, notamment, par une oxydation allylique de la double liaison terminale de ce composé et une méthoxycarbonylation catalysée au palladium de manière à introduire un équivalent du groupe hydroxyméthyle. Pour la (+)-hyacinthacine A1, un groupement hydroxyméthyle masqué est introduit par addition d'un cuprate de phényldiméthylsilylméthyle sur un imminium intermédiaire provenant du même lactame. Ce groupement est alors converti en hydroxyméthyle, en fin de synthèse, par une oxydation de Tamao-Fleming.

Hannover, University, Diss., 2007.

Orientador: Cristiane Damas Gil / Coorientador: Sonia Maria Oliani / Banca: Eloísa Amália Vieira Ferro / Banca: Newton Antonio Bordin Jr / Resumo: A endometriose é uma doença inflamatória crônica, de etiologia multifatorial caracterizada pela implantação e crescimento do endométrio fora da cavidade uterina (endométrio ectópico). Nas lesões de endometriose, os mastócitos aparecem em elevado número, no entanto, poucos estudos investigaram seus mediadores inflamatórios na patogênese dessa doença. Entre os mediadores dos mastócitos ressaltamos a anexina A1 (ANXA1), proteína de 37 kDa com múltiplas ações biológicas como inibição da transmigração de leucócitos, proliferação celular e apoptose. Tais efeitos são mediados por receptores para peptídeos formilados (FPRs), especialmente FPR1. Assim, o objetivo desse trabalho foi investigar o papel das células inflamatórias, particularmente a ativação e heterogeneidade dos mastócitos, sua correlação com a expressão e o mecanismo de ação da ANXA1 em biópsias de endométrios eutópicos (controle, n=10) e ectópicos (endometriose de parede abdominal, n=18). As amostras de endométrio ectópico foram coletadas entre julho de 2003 e janeiro de 2012, incluídas em parafina e cedidas pelo Departamento de Patologia da FAMERP. As biópsias de endométrios eutópicos foram coletadas de pacientes sem quadro clínico de endometriose, entre junho de 2011 e junho de 2012, com a colaboração do Departamento de Ginecologia e Obstetrícia da FAMERP. Essas biópsias foram processadas para: (i) análises histopatológicas, (ii) quantificação de células inflamatórias (neutrófilos e mastócitos) e (iii) imuno-histoquímica utilizando anticorpos específicos para estudo da heterogeneidade dos mastócitos (triptase e quimase), da expressão da ANXA1 e do receptor FPR1 nos tecidos. A análise histopatológica das lesões de endometriose mostrou... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Endometriosis is a chronic inflammatory disease of multifactorial etiology, characterized by implantation and growth of endometrium outside the uterine cavity (ectopic endometrium). Endometriotic lesions presented a high number of mast cells, however, few studies have investigated their inflammatory mediators in the pathogenesis of this disease. Among these mediators we emphasize annexin A1 (ANXA1), a 37 kDa protein with multiple biological actions like inhibition of leukocyte transmigration, cellular proliferation and apoptosis. Such effects are mediated by formyl peptide receptors (FPRs), especially FPR1. Thus, the purpose of this study was to investigate the role of inflammatory cells, particularly the activation and heterogeneity of mast cells, and its correlation with expression and mechanism of action of ANXA1 in biopsies of eutopic (control, n = 10) and ectopic endometrium (abdominal wall endometriosis; n = 18). The samples of ectopic endometrium were collected between July 2003 and January 2012, embedded in paraffin and provided by the Department of Pathology of FAMERP. Biopsies of eutopic endometrium were collected from patients without clinical features of endometriosis, between June 2011 and June 2012, with the contribution of the Department of Obstetrics and Gynecology of FAMERP. These biopsies were processed for: (i) histopathology, (ii) the quantification of inflammatory cells (neutrophils and mast cells) and (iii) immunohistochemistry using specific antibodies to study the heterogeneity of mast cells (chymase and tryptase), and expression of ANXA1 and FPR1 receptor in tissues. Histopathological analysis of endometriotic lesions showed two morphological patterns: glandular pattern of mixed differentiation (presence of differentiated glands with simple prismatic epithelium and... (Complete abstract click electronic access below) / Mestre

During cellular stress, the regulation of protein synthesis is a key adaptive mechanism used by cells to survive. In response to various stresses, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), an RNA binding protein principally found within the nucleus, is phosphorylated and consequently accumulates in the cytoplasm. Among other roles, cytoplasmic hnRNP A1 functions as an auxiliary translation factor for internal ribosome entry site (IRES)-mediated translation of specific mRNA, including the anti-apoptotic protein B-cell lymphoma-extra large (Bcl-xL). To identify which kinases control the cytoplasmic accumulation of hnRNP A1, an RNAi-based kinome-wide screen was performed in hypertonically stressed U2OS cells, from which AMPK-related kinase 5 (ARK5) was identified as a potential regulator of hnRNP A1’s localization. Here we show that ARK5 directly phosphorylates hnRNP A1 and that the inhibition of ARK5 expression blocks the stress induced cytoplasmic accumulation of hnRNP A1, modulates expression of Bcl-xL protein and increases cell viability. Our data points to a novel role for ARK5 and provides further insight into the mechanisms regulating cellular stress response.

Patente de tipo Aplicación (US20180245954A1). 30 de Agosto de 2018. / The invention relates to an instrument for measuring air speed by means of parabolic movement and to a measuring method, wherein the measuring instrument is formed by a cubic structure (1) that holds a screwable, flexible container (2) which releases—where air speed needs to be measured—a drop of liquid, the drop falling on one of the concentric circles located on an interchangeable plate (3) that is positioned on a flat base (4) of the device and perpendicular to the axial end of the outlet for the drop of liquid. Depending—on the height—the movement with which the drop falls, the air speed can be determined by means of the horizontal range of the parabolic movement followed by the drop of liquid, and evaluated using the distance be ween the point of impact of the drop on the surface with respect to the center. The direction of the air speed can also be determined from angle formed by the projection of the vertical plane above which projection the air moves in relation to the x-axis of the x-y plane located above the interchangeable plate (3).

O processo de hidrogenação vegetal utilizado pelas indústrias alimentícias tem provocado o aumento no consumo de ácidos graxos trans (AGT). Estudos epidemiológicos confirmaram correlação positiva entre ingestão de AGT e risco de doenças cardiovasculares. Nesse contexto, surge como alternativa o óleo de palma, livre de AGT. Embora há evidências dos efeitos da ingestão de AGT no sistema cardiovascular, faltam estudos que avaliem o impacto do conteúdo lipídico da dieta no Sistema Nervoso Central. A adenosina é um neuromodulador que pela ligação nos seus receptores A1 (inibitórios) e A2A (facilitatórios) participa de vários sistemas de neurotransmissores, como dopamina, noradrenalina e glutamato. Nosso objetivo é verificar alterações comportamentais e neuroquímicas em ratos adultos que receberam dieta normolipídica, contendo AGT ou óleo de palma, desde o período gestacional. Três grupos de ratas Wistar receberam dietas normolipídicas diferindo a fonte lipídica: óleo de soja (OS; controle); óleo de palma (OP); gordura hidrogenada/trans (GT). Após duas semanas de adaptação à dieta e acasalamento, as fêmeas receberam a mesma dieta até o final da lactação. No desmame, filhotes machos continuaram com a mesma dieta até 60 dias pós-natal. Para avaliar parâmetros de ansiedade e atividade locomotora nos ratos com 2 meses de idade, foram realizados os testes de labirinto em cruz elevado (LCE) e arena em campo aberto (CA), respectivamente. Esquiva inibitória (EI) e reconhecimento de objetos (RO) foram realizados para teste de memória e aprendizado. Após 24h, os animais foram sacrificados e córtex, hipocampo e hipotálamo separados para análise da densidade de receptores A1 por Western Blot. No LCE, os animais que receberam a dieta GT permaneceram mais tempo nos braços abertos em comparação aos grupos que receberam as dietas OS e OP. Os grupos OP e GT fizeram menor número de cruzamentos comparados ao grupo OS no CA. Os grupos OP e GT tiveram a memória de curta duração prejudicada na EI e no RO, comparados ao grupo OS. Houve um prejuízo na memória de longa duração somente no grupo OP na EI. Observou-se diminuição significativa de 39% na densidade do receptor A1 no hipocampo de ratos que receberam GT (P=0,0335). No hipotálamo, ratos que consumiram a dieta OP apresentaram um aumento significativo de 15% na densidade do receptor A1, comparado ao grupo OS (P=0,0031). Não houve alterações neuroquímicas no córtex dos ratos submetidos às dietas do estudo. Nossos resultados revelaram que os filhotes submetidos à dieta rica em AGT desde o período intrauterino apresentaram menor ansiedade, menor atividade locomotora e declínio na memória de curta duração na idade adulta, enquanto os animais que receberam OP no mesmo período não alteraram o comportamento de ansiedade, mas tiveram menor atividade locomotora e declínio cognitivo na memória de curta e de longa duração. Também foram encontradas alterações no imunoconteúdo dos receptores de adenosina A1 em diferentes estruturas cerebrais e conforme o tratamento dietético. Este estudo sugere a importância da qualidade lipídica da dieta oferecida desde o período gestacional, que pode estar relacionada a comportamento de ansiedade e desempenho cognitivo na idade adulta. / Dietary consumption of trans fatty acids (TFA) has increased during the 20th century, due to the increasing use of vegetal oil hydrogenation by food industries, which product is hydrogenated fat. Epidemiolgy studies have shown that TFA intake is correlated to risk for cardiovascular diseases. Thus, palm oil has emerged as an alternative to hydrogenated fat. Eventhough studies are advanced in cardiovascular research, the impact of dietary fat intake in Central Nervous System are still lacking. Adenosine is a neuromodulator which via its metabotropic receptors A1 and A2A participates in the neurotransmission of some neurotransmitters such as dopamine, noradrenaline and glutamate. The aim of the present study was to investigate whether intake of different diets from early pregnancy until adult life of offspring could promote behavioral and neurochemical alterations. Wistar female rats were divided into three groups and received isocaloric/normolipidic diets with soybean oil (SO, control diet), palm oil (PO) or hydrogenated-trans fat (TF) as a fat source, during pregnancy and lactation. After weaning, male pups continued receiving the same diet up to 60 days-old. Elevated plus-maze (EPM) was chosen to evaluate anxiety-like behavior and open field task (OF) to verify locomotor activity. For learning and memory analysis, we chose a non-aversive (Object Recognition Task, OR) and an aversive task (Inhibitory Avoidance, IA). The immunocontent of adenosine receptors in cortex, hippocampus and hypothalamus were studied by Western Blot. In EPM, rats receiving TF diet spent more time in the open arms, comparing to SO and PO groups. In OF, number of crossing was significantly lower both in TF and PO groups, comparing to SO group. We also found short-term memory impairment in both memory tasks in rats fed PO and TF diet, whereas long-term memory was modified only in animals receiving PO diet. Neurochemical alterations were found in adenosine receptor A1 in hippocampus of animals fed TF diet, with a significant 39% decreasing in the immunocontent comparing with SO diet (P=0,0335); and in hypothalamus from PO group, with a significant 15% increasing in the immunocontent (P=0,0031). The offspring exposed to TF diet during development were less anxious, presented lower locomotor activity and impairment in short-term memory in adulthood, whereas PO group had similar alterations, except that of anxiety. We also found alterations of adenosine receptor immunocontent in different brain areas that were dependent of the type of fat source. This work suggests the importance of the quality of fat source during development up to adulthood, which may be related in anxiety behavior and cognitive performance in memory tasks.

A cafeína é o psicoestimulante mais consumido mundialmente. Sua ação farmacológica consiste em bloquear os receptores de adenosina A1 e A2A. A administração crônica de cafeína previne déficits cognitivos decorrentes da idade e em modelos experimentais da doença de Alzheimer. Esses efeitos preventivos são também observados pela administração do antagonista seletivo do receptor de adenosina A2A. Nesse trabalho investigou-se a participação dos receptores de adenosina A1 e A2A na prevenção dos déficits cognitivos induzidos por escopolamina. Também foi investigado se a manipulação dos receptores A2A teria algum impacto na memória em camundongos naive. Para isso, foram utilizadas três tarefas comportamentais que avaliaram três tipos de memória: a tarefa de reconhecimento de objetos (RO), a esquiva inibitória (EI) e o labirinto em Y. A administração intraperitoneal de escopolamina (1,0 mg/kg) prejudicou o desempenho da memória de curto prazo nas três tarefas utilizadas. O antagonista de receptores A1 (DPCPX, 1,0 mg / kg, i.p.) preveniu a amnésia induzida por escopolamina no RO e na EI, enquanto o antagonista de receptores A2A (SCH 58261, 0,5 mg / kg, i.p.) preveniu a amnésia em todos os testes. Além disso, ambos os antagonistas não apresentaram efeitos sobre a memória ou a locomoção em animais naive. Também foi observado que a ativação dos receptores A2A, a partir da administração de CGS 21680 (0,1 mg/kg, i.p.) antes da sessão de treino, foi suficiente para provocar prejuízos na memória em animais naive também nas três tarefas, e este efeito foi prevenido por meio da administração de SCH 58261 (0,5 mg/kg, i.p.). Por fim, a administração intracerebroventricular (i.c.v) de CGS 21680 (50 nmol) também prejudicou o desempenho dos animais na tarefa de RO. Em conjunto, estes resultados sugerem que a ativação dos receptores A2A é suficiente para provocar déficits de memória e ainda sugerem que os receptores A1 também participam de maneira seletiva no controle dos déficits de memória relacionados ao sistema colinérgico. / Caffeine, a non-selective adenosine receptor antagonist, prevents memory deficits, an effect mimicked by adenosine A2A receptor (A2AR), but not receptor A1 (A1R), antagonists upon aging and Alzheimer´s disease. We tested if A2AR were also necessary for the memory impairment upon direct perturbation of the cholinergic system with scopolamine and if A2AR activation was sufficient to trigger memory deficits in naive mice using 3 tests, to probe for short-term memory, namely the object recognition task, inhibitory avoidance and modified Y-maze. The intra-peritoneal (i.p.) administration of scopolamine (1.0 mg/kg) impaired short-term memory performance in 3 tests, namely the object recognition task, inhibitory avoidance and modified Y-maze. The scopolamine-induced amnesia was prevented by the A2AR (SCH 58261, 0.5 mg/kg, i.p.) as well as by A1R antagonist (DPCPX, 1 mg/kg, i.p.) in all tests, except for the modified Y-maze, and both antagonists were devoid of effects on memory or locomotion in naive rats. Notably, the activation of A2AR with CGS 21680 (0.1 mg/kg, i.p.) before the training session was sufficient to trigger memory impairment in the 3 tests in naive mice, and effect prevented by SCH 58261 (0.5 mg/kg, i.p.). Furthermore, the intracerebroventricular administration of CGS 21680 (50 nmol) also impaired recognition memory in the object recognition task. These results show that A2AR are necessary and sufficient to trigger memory impairment and they further suggest that A1R might also be selectively engaged to control the cholinergic driven memory impairment.