Programa de Pós-Graduação em Neurociências e Biologia Celular - PPGNBC/ICB

URI Permanente desta comunidadehttps://repositorio.ufpa.br/handle/2011/2374

O Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) é parte integrante do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA), sendo constituído por: Mestrado e Doutorado em Neurociências e Biologia Celular, com área de concentração em Neurociências ou Biologia Celular.

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Acesso aberto (Open Access)
Análise da proteção de citocinas após exposição celular in vitro com os antígenos ML2478 e ML0840 do Mycobacterium leprae
(Universidade Federal do Pará, 2019-09) MESSIAS, Ana Caroline Cunha; SALGADO, Claudio Guedes; http://lattes.cnpq.br/2310734509396125; http://orcid.org/0000-0003-3961-7764
Diagnosis of oligosymptomatic leprosy cases may enable interventions to be performed before the onset of physical disabilities. However, because the diagnosis is still essentially clinical and the disease progresses slowly, there is difficulty in recognizing these cases, since the lesions are discreets and with subtle changes in sensitivity. Most of the time patients are diagnosed when they already have obvious clinical characteristics and/or physical disabilities. Thus, is necessary to develop laboratory tools that help in the early diagnosis of the disease. The cell immunity assay Whole Blood Assay (WBA) is a low-cost, easy-to-perform technique that provides conditions for antigen screening and is favored in areas where leprosy is endemic and may facilitate incorporation of a test into sites with less access to sophisticated laboratories. The objective of this study was to evaluate the cellular immune response after in vitro exposure of peripheral blood to Mycobacterium leprae antigens ML2478 and ML0840. Eighty-seven individuals were selected for quantitation the cytokines of Interferon-γ (IFN-γ), Interleukin (IL)-10, IL-17 and Transforming Growth Factor-β1 after exposure with specific M. leprae antigens by WBA for 24 hours. A total of 47 leprosy cases were evaluated distributed in: 6 tuberculoid and 14 borderline tuberculoid, 13 borderline lepromatous leprosy, 6 lepromatous leprosy; and 8 schoolchildren diagnosed with leprosy during the group active search strategy (oligosymptomatic cases in the clinical forms: 1 primary neural, 1 undetermined, 6 borderline tuberculoid). The remaining 47 individuals corresponded to 20 contacts, 13 healthy schoolchildren and 7 individuals with other skin diseases. The analysis of cytokines suggests the balance between IFN-γ and IL-10 may indicate individuals who are progressing to the Th2 pole. IL-17 and TGF-β1 may be used to follow-up individuals with similar response to leprosy cases. The production of IFN-γ, IL-10, IL-17 and TGF-β1 cytokines by stimulation with proteins ML2478 and ML0840 did not differ between healthy students and case students. And the cytokine IL-17 demonstrated higher production in cases attended at URE than in case students and individuals in control groups.
Acesso aberto (Open Access)
Ativação do receptor canabinóide tipo 1 (CB1r) previne o estresse oxidativo cerebral e inibe o comportamento tipo agressivo em Danio rerio (Zebrafish)
(Universidade Federal do Pará, 2022-08-17) PINHEIRO, Emerson Feio; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
Aggression is a set of complex actions that involve several factors of a genetic, neurophysiological, hormonal and behavioral nature. Furthermore, the brain redox state can also influence aggressive behavior in different species. Thus, modulators of this process can influence the expression of aggressive episodes, between them is the Endocannabinoid System that acts as the main neuromodulator of the CNS, in addition to exerting an antioxidant effect in different conditions. However, its participation in the modulation of aggressive-like behavior needs to be better understood. In this context, this study evaluated the role of cannabinoid receptor type 1 (CB1r) in brain redox state and aggressive-like behavior in Danio rerio (Zebrafish). For this, 64 animals were subdivided into groups: (a) Control (n=26), (b) ACEA (n=30) and (c) AM-251 (n=12), all treated with the drugs of interest: (a) Vehicle (NaCl 0.9%); (b) ACEA agonist 1 mg/kg; (c) 1 mg/kg AM-251 antagonist. The animals were isolated in pairs, without physical contact for 24 hours, followed by pre-treatment and after 30 minutes of pharmacokinetics, the fights were filmed for 30 minutes, the individuals were identified as Dominant or Subordinate and the brains were collected for evaluation of the state brain redox of these individuals. Our results demonstrate, for the first time, that the activation of CB1r by the ACEA agonist modulates aggressive-like behavior and, consequently, partially interferes with the establishment of social hierarchy in Zebrafish, through a redox-independent mechanism. We suggest, therefore, that acute treatment targeting CB1r is a useful neuropharmacological tool to elucidate the role of CES in social interaction and aggressive behavior, allowing a translation with numerous pathologies that have aggression as a behavioral disorder.
Acesso aberto (Open Access)
Atividade antineoplásica da 1-desoxinojimiricina em modelos de câncer in vitro
(Universidade Federal do Pará, 2021-12) FONSECA, Suzanne Suely Santos da; PEREIRA JÚNIOR, Antônio; http://lattes.cnpq.br/1402289786010170; https://orcid.org/0000-0002-0808-1058
Cancer is one of the diseases that kill the most in Brazil, with alarming projections until 2030. In view of the problems related to cancer treatment, such as the compromise of healthy cells and, consequently, the presence of adverse effects, it is imperative to seek of alternative substances that may have antineoplastic effects and that are effective in the treatment of patients with this disease. In this way, the use of bioactive compounds has been widely used in the fight against neoplasms. Thus, the substance 1-deoxynojimyricin (1-DNJ) isolated from Bagassa guianensis may have great anticancer potential. In view of the problems related to cancer treatment, such as the impairment of healthy cells and, consequently adverse effects, it is necessary to search alternative substances that may have antineoplastic effects and they are effective in the treatment of patients with this disease. The objective of this study was to evaluate the effect of 1-deoxynojirimycin (1-DNJ) extracted from wood residue of the species Bagassa guianensis in different cancer cell lines to investigate possible antineoplastic actions in vitro using gastric adenocarcinoma and glioblastoma cancer cell lines. To do that, it was evaluated the effect of the substance 1-deoxynojirimycin on cell viability in vitro after 72h of treatment in cell lines ACP02 and A172. We also evaluated the effect of this bioactive compound on cell migration pattern, cell death by apoptosis and cell cycle changes using flow cytometry and reactive oxygen production. The results showed that 1-deoxynojirimycin makes a significant reduction in cell viability of cancer cell cultures in both glioblastoma (A172) and gastric cancer cell (ACP02) cell lines. The reduction in viability appears to be more effective in glioblastoma cell lines, with a common ic50 much lower when compared to other cell lines. We propose that the reduction in viability may be related to the decrease in reactive oxygen production in both lines after treatment with 1-DNJ. Besides that, 1-DNJ interrupts the cell cycle, prevents cell migration and induces necrosis-like cell death in the ACP02 lineage and apoptosis in the A172 lineage. Therefore, we suggest that 1-deoxynojirimycin may be an important and effective chemopreventive substance for the treatment of glioblastoma and gastric adenocarcinoma cancers.
Acesso aberto (Open Access)
Avaliação da seletividade olfatória causada pela infecção por SARS-COV-2
(Universidade Federal do Pará, 2022-09-16) ALMEIDA, José Ramon Gama; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806; ÁVILA, Paulo Eduardo Santos; http://lattes.cnpq.br/4673218055614655
Introduction: Sudden loss of smell is one of the most prevalent symptoms of COVID-19. The sense of smell ranges from detecting warning odors in the environment to building our most pleasurable experiences. This sense stimulates a complex neural network, including the temporal lobe, the amygdala, the insula and a large part of the limbic lobe: the loss of smell should not, only, be considered a sensory symptom, but also a psycho-sensory syndrome. Objectives: This study was aimed to evaluate the olfactory selectivity and trigeminal sensation in olfactory alterations reported by patients diagnosed with COVID-19. Methods: The Randomized case-control study involving 88 individuals: COVID-19 without olfactory dysfunction previously diagnosed prior to the pandemic period; with COVID-19 with olfactory dysfunction diagnosed before the pandemic period; and without COVID-19 and loss of olfactory sensitivity during the pandemic period, with persistent anosmia or hyposmia after SARS-CoV-2 infection. All individuals participating in the study (Control/intervention groups) diagnosed with or without COVID-19 underwent evaluation data collection form and psychophysical sensory test which included olfactory test, olfactory memory test, olfactory threshold test and trigeminal sensation test (CEP-UFPA: 40962420.2.0000.0018). ANOVA follow the Tukey test. Results: The results demonstrated which all patients with or without COVID-19 diagnosis, loss the ability to not identify the odorant of banana essence when compared to the healthy health group being significant control vs. COVID-19 without p<0.0002 and significant control vs. COVID-19 with p<0.0010 and not significant COVID-19 without vs. COVID-19 with p>0.05. For the short-term olfactory memory test which all patients with or without COVID-19 diagnosis, demonstrated an increase in the misidentification of odorants presented when compared to healthy controls, as well as in the olfactory threshold differences in perception were observed between the groups. analyzed. The absence of at least one chemosensory function (cooling sensation) of the trigeminal during the test period was reported by which all patients with or without COVID-19 diagnosis, when compared to the healthy control group. Conclusion: In this way, SARS-CoV-2 infection may be promoting an olfactory dysfunction that affects the perception of banana odor, as well as the affected long-term characteristic such as olfactory memory, olfactory threshold and trigeminal sensation of olfactory loss that COVID-19. 19 generates in patients may provide clues to therapeutic interventions aimed at preventing, alleviating or curing long-term olfactory dysfunction in COVID-19.
Acesso aberto (Open Access)
Avaliação do potencial neuroprotetor do beta-cariofileno em modelo murino de Doença de Parkinson induzido por 6-Hidroxidopamina
(Universidade Federal do Pará, 2019-06) AMARAL, Anderson Valente; YAMADA, Elizabeth Sumi; http://lattes.cnpq.br/7240314827308306
Parkinson’s disease (PD) is classified as a motor disturbance characterized by resting tremor, muscular rigidity, postural instability and bradykinesia. These symptoms are caused by progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and consequently depletion of dopamine on striatum (STR). The search for new therapeutical approaches that may delay or interrupt the neurodegeneration in PD is essential to promote a better quality of life for patients. Thus, we investigated whether beta-caryophyllene (BCP) has neuroprotective effects in the 6-OHDA murine model of PD. Then, we performed behavioral tests such as apomorphine-induced rotations and exploration in the open field, we measured the optical density from STR fibers, quantified neurons and microglia in the SNpc through stereology and evaluated the total antioxidant capacity from STR and midbrain. Our evidence demonstrates that BCP reduced the degree of neurodegeneration induced by 6-OHDA, improved motor performance, protected striatal dopaminergic fibers, protected dopaminergic neurons and reduced microglial activation in the SNpc. But did not alter the antioxidant capacity in the STR and midbrain. Hence, BCP treatment has a potential neuroprotective effect in this mouse model of PD, which deserves to be better characterized for translational application.
Acesso aberto (Open Access)
Caracterização química, avaliação da toxicidade oral aguda e da atividade antinociceptiva do extrato metanólico das folhas de Montrichardia linifera (Arruda) Schott
(Universidade Federal do Pará, 2024-08) COSTA, Wellington Junior Taisho Nagahama; AMARANTE, Cristine Bastos do; http://lattes.cnpq.br/4101983776191966; https://orcid.org/0000-0002-8602-8180; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
Background: Montrichardia linifera (Arruda) Schott is popularly known as “aninga”, “aningaçu”, “aningaíba” and “aninga-do-igapó”. The compresses and plasters from the leaves of the medicinal plant are used to treat abscesses, tumors and pain caused by stingray stings. Aim of the study: The study aimed to investigate the antinociceptive potential of the methanolic extract of Montrichardia linifera leaves (MEMLL), as well as carry out chemical characterization and acute oral toxicity. Materials and methods: The leaves were collected during the rainy season and the methanolic extract was obtained after gradient extraction in different solvents. The MEMLL was analyzed using high performance liquid chromatography (HPLC) and Nuclear Magnetic Resonance (NMR). The evaluation of the acute oral toxicity test was used to observe the presence of toxic substances. Subsequently, acetic acid, hot plate and formalin tests were used to evaluate the analgesic effects. Results: The HPLC fingerprint analysis allowed the identification of rutin, quercetin and epicatechin. The analysis of NMR spectra identified rutin and quercetin, as well as the flavonoids luteolin and chrysoeriol. The MEMLL did not demonstrate effects considered toxic. In the acetic acid test, the MEMLL inhibited peripheral pain by 51.46% (p < 0.05) at a dose of 50 mg/kg and 75.08% (p < 0.001) at a dose of 100 mg/kg. The hot plate test evaluated the latency time of animals, demonstrating central activity at 30 and 60 min increasing by 164.43% (p < 0.01) and 122.95% (p < 0.05) at a dose of 50 mg /kg and 162.62% (p < 0.01) and 136.68% (p < 0.05) at a dose of 100 mg/kg. The formalin test evaluated the central and peripheral antinociceptive effect of the MEMLL. In the neurogenic phase, a reduction of 35.25% (p < 0.05) at a dose of 50 mg/kg and 52.30% (p < 0.01) at a dose of 100 mg/kg. In inflammatory pain, a reduction of 66.39% (p < 0.0001) and 72.15% (p < 0.0001) was observed. Conclusion: The antinociceptive activity supports its ethnopharmacological use. This analgesic effect is probably associated with the identified flavonoids, all of which have antioxidant, anti-inflammatory and antinociceptive properties. Furthermore, the MEMLL was non-toxic.
Acesso aberto (Open Access)
Efeitos anti-inflamatórios e neuroprotetores do extrato de gergelim preto (Sesamum indicum L.) em um modelo experimental de isquemia estrial
(Universidade Federal do Pará, 2024-03) SANTOS, Ijair Rogério Costa dos; LEAL, Walace Gomes; http://lattes.cnpq.br/2085871005197072
Acidente Vascular Encefálico (AVE) é uma neuropatologia caracterizada como o surgimento súbito global ou focal de déficits da função neurológica de duração superior a 24 horas ou que leve a morte, cuja única causa reside na origem vascular. Estudos sobre a incidência, comprometimento físico e mortalidade enquadram o AVE como a segunda causa de morte no mundo e a principal complicação orgânica que leva às disfunções físico-neurológicas, frequentemente, graves e permanentes. A indução do AVE em animais de experimentação e o entendimento de sua fisiopatologia, bem como a busca de tratamentos que minimizem os danos neurológicos e estimulem a recuperação morfofuncional do indivíduo afetado são temas de grande relevância científica e clínica. Neste estudo, investigamos os possíveis efeitos neuroprotetores e/ou anti-inflamatórios do extrato supercrítico de gergelim preto (Sesamun indicum L.) após lesão isquêmica focal por microinjeções de 80 pmol de endotelina-1 no estriado de ratos adultos, usando as coordenadasestereotáxicas: 1,2 mm, anterior-posterior; 2,5 mm, médio-lateral; 4,0 mm, dorsoventral. Após a indução do AVE, os grupos controles foram tratados com tween a 5% e os tratados receberam 150 mg/kg de gergelim, ambos, por via intraperitoneal, em duas doses diárias de 75 mg/kg. A neuropatologia foi obtida em secções encefálicas com 50 e 20 μm de espessuras e coradas com violeta de cresila, para identificar a área de lesão, e/ou imunomarcadas por anticorpos específicos à identificação de neurônios (anti-NeuN), astrócitos (anti-GFAP) e micróglia (anti-ED1). Secções de 5 μm de espessura de rim e fígado corados por métodos histológicos e histoquímicos não mostraram alterações morfológicas nas células que compõem esses órgãos essenciais, sugerindo baixa toxicidade do extrato. Todas as secções coradas e/ou imunomarcadas foram visualizadas em microscópio óptico e seuscampos mais ilustrativos, em todos os tempos de sobrevida e grupos experimentais,foram capturados digitalmente e editados em computador. A quantificação das célulasNeuN+(neurônios), micróglia/macrófagos (ED1+) e astrócitos (GFAP+) na área de lesão, três secções por lâmina, todo campo ao redor de lesão por secção, com auxílio de uma gradícula de área 0,0625 mm2 na ocular possibilitou o teste t-Student à análise estatística entre os grupos e o uso do programa Microsoft Excel à plotagem dos gráficos. Por fim, uma caracterização da citotoxicidade in vitro, bem como a verificação do índice de acidez do extrato revelou baixa acidez e mínima agressividade em células sanguíneas, que ratifica o uso do extrato supercrítico em estudos que visem otratamento de doenças agudas e crônicas no SNC.
Acesso aberto (Open Access)
Efeitos da suplementação com açaí clarificado (Euterpe oleracea Mart.) sobre marcadores de estresse oxidativo em pacientes com doença renal crônica em hemodiálise
(Universidade Federal do Pará, 2019-06) MARTINS, Isabelle Christine Vieira da Silva; NASCIMENTO, José Luiz Martins do; http://lattes.cnpq.br/7216249286784978; https://orcid.org/0000-0003-3647-9124
Acesso aberto (Open Access)
Efeitos do tratamento agudo sistêmico de beta-cariofileno em camundongos fêmea saudáveis e em modelo de inflamação sistêmica
(Universidade Federal do Pará, 2021-07) MONTEIRO, Rayan Fidel Martins; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
All the functions of the endocannabinoid system (ECS) are not yet fully understood, however this system is known to have a neuromodulatory effect, essentially attributed to cannabinoid type I receptors (CB1R), which systemic activation induces psychoactive effects. In contrast, the immunomodulatory effect of ECS, attributed mainly to cannabinoid type II receptors (CB2R), has been demonstrated as an alternative treatment for several acute or chronic inflammatory diseases, including neurodegenerative diseases in animal models via chronic CB2R activation. However, the effects of this treatment are still unclear shortly after its administration. In this sense, we seek to investigate the effects of the acute-systemic treatment of β-caryophyllene (BCP), a phyto-cannabinoid agonist of CB2R in a murine model of neuroinflammation induced by LPS. We performed the open field test (OF) 2 and 4 h after the induction of sickness behavior by Lipopolysaccharide (LPS) and demonstrated that in animals pretreated with BCP, in the 2 h window, there was maintenance in the quality of movement in animals that received LPS without alteration in the induction of sickness behavior, and increased activity in the aversive region of the apparatus in animals that did not receive LPS. Indicating the immune and neuromodulatory effect of BCP. We also performed the Morris Water Labyrinth (MWM) test 24 h after inoculation of LPS, however it was not possible to discriminate changes in learning, however the inoculated and untreated animals proved to be more likely to form spatial memory. Finally, we observed that pretreatment with BCP increases lipid peroxidation and nitrite concentration in the brain 2 h after LPS inoculation, thus suggesting an immediate increase in oxidative stress by acute treatment with BCP in neuroinflammatory models. Therefore, it is of fundamental importance to continue researching the immediate neurological and immunological effects of BCP treatment in healthy animal models and in neuroinflammatory models for better determination of the risks attributed to this treatment, as well as the addition of acute treatment to the detriment of the treatment. chronic in different neurological pathologies.
Acesso aberto (Open Access)
Glutationa modula a liberação de adenosina em cultura primária de astrócitos corticais de camundongo
(Universidade Federal do Pará, 2022-09-06) SILVA, Mateus dos Santos; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369; SILVA, Anderson Manoel Herculano Oliveira da; http://lattes.cnpq.br/8407177208423247
Glutathione (GSH) is one of the main antioxidants in the Central Nervous System (CNS) and a potential gliotransmitter, inducing calcium waves in the cytosol of glial cells. Adenosine (Adn) is a neuromodulator widely expressed in the CNS and its extracellular levels are a critical factor in determining its effect on nervous tissue. It is known that Ca2+- dependent pathways regulate Adn release. Since GSH has the ability to induce Ca2+ waves in the cytosol of glial cells, the present work aims to investigate whether this molecule can regulate extracellular DNA levels. To assess this, we used primary cultures of cortical astrocytes maintained in DMEM+10% SBF in a CO2 oven (37oC, 95% O2/5% CO2) for 12-15 days, when they reached confluence. The cells were incubated with Hank buffer for different time intervals, after which this solution was collected and the neurotransmitters present there were quantified by High Performance Liquid Chromatography. Our data show that GSH induces an 80% increase in extracellular Adn levels at two analyzed times: 5 and 20 minutes. Removal of GSH from the incubation medium returns the Adn concentration to baseline levels. Removal of Na+ or Ca2+ from the medium did not affect the effect of GSH. Blockade of nucleoside equilibrative transporters by dipyridamole (10 µM) significantly decreased the levels of Adn in the medium, but did not interfere with the action of GSH. In order to assess whether the effect of GSH derives from an indirect modulation on the release of glutamate or GABA (two agents described as regulators of Adn release), the quantification of these transmitters was performed. Both were significantly increased in the presence of GSH. However, unlike what was observed with Adn, the removal of Na+ from the incubation medium mitigated the effect of GSH on glutamate release. The incubation of astrocytes with GABA (50 and 100 µM) did not influence the extracellular Adn concentration in our experimental model, ruling out a GABAergic modulation behind the effect of GSH. The evaluation of redox agents showed that thiol compounds reproduce the effect of GSH, while the non thiol antioxidant alpha-tocopherol did not regulate extracellular Adn levels. Thus, the present work concludes that astrocytes express a GSH-sensitive component that can be modulated by its sulfhydryl group.
Acesso aberto (Open Access)
Inibição de ciclooxigenase-2 (COX-2) em camundongos infantis saudáveis: consequências sobre o comportamento e o perfil oxidativo
(Universidade Federal do Pará, 2022-08-26) LIMA, Klinsmann Thiago; BASTOS, Gilmara de Nazareth Tavares; http://lattes.cnpq.br/2487879058181806
In the central nervous system, cyclooxygenase 2 (COX-2) is a constitutive enzyme, expressed by neurons from different brain regions, which acts in the maintenance of neural homeostasis, modulating synaptic plasticity and the generation of new neurons. Non-steroidal anti-inflammatory drugs (NSAIDs) are drugs of choice that act to inhibit COX enzymes, with nimesulide (NMS) being a drug of this class. Several studies have demonstrated the role of these enzymes in neurological and neuropsychiatric disorders such as Parkinson's Disease, Alzheimer's Disease, epilepsy, depression and schizophrenia. Thus, the aim of the present work was to investigate the effects of COX- 2 inhibition in healthy infant mice on behavioral and biochemical criteria, using NMS as a pharmacological blockade tool. For this, male Swiss infant mice, aged between 21 and 34 days, were used. The animals were randomly divided into four groups: (1) Vehicle, (2) NMS 2.5mg/kg, (3) NMS 5mg/kg and (4) NMS 10mg/kg. Two injections of NMS/Vehicle were administered intraperitoneally daily. Throughout the experiment, the body mass of the animals was recorded daily and they were subjected to behavioral tests: open field test (OFT), elevated plus maze (EPM), light/dark box test (LDBT) and novel object recognition test (NORT). In addition, brain samples were collected for biochemical analyses. The results demonstrated the induction of oxidative stress with increased levels of lipid peroxidation in the cortex and hippocampus, as well as the expression of an anxiogenic behavior, observed in the EPM, possibly potentiated by fear. In the NORT, the animals of the NMS 5mg/kg group showed a deficit in the memory of recognizing new objects, and consequently, in the short-term memory. Thus, our results demonstrated that the in vivo inhibition of COX-2 in infant animals induces an anxious-like behavior possibly potentiated by fear, but does not affect the exploration and locomotion of these animals. Furthermore, COX-2 inhibition induced cortical and hippocampal oxidative stress. Therefore, the inhibition of COX-2 in infantile and non-inflamed animals may compromise cognitive functions such as memory and learning, as well as alter the cerebral oxidative profile.
Acesso aberto (Open Access)
Investigação dos efeitos da cafeína e SCH58261 sobre as alterações comportamentais e no estresse oxidativo, e papel dos receptores A2A na potenciação de longo prazo após intoxicação por etanol em padrão binge em ratos fêmeas da adolescência a fase adulta
(Universidade Federal do Pará, 2022-11) PINHEIRO, Bruno Gonçalves; MAIA, Cristiane do Socorro Ferraz; http://lattes.cnpq.br/4835820645258101
Introduction: Binge consumption of ethanol is an intermittent and episodic pattern of ingestion involved in several brain disorders that affect adolescents, considered more susceptible to damage that persists into adulthood. In the deleterious effects of ethanol, an important intoxication mechanism is the overproduction of adenosine, which causes hyperexcitability in its receptors, generating behavioral changes and oxidative stress. These receptors are antagonized by caffeine, a bioactive compound that can modulate the deleterious overactivation of ethanol. Objective: The aim of this study was to investigate the effects of caffeine administration on behavioral changes related to locomotion, anxiety, cognition and oxidative balance induced by ethanol in the binge drinking pattern during adolescence. In addition, it aims to assess the contribution of A2A receptors in the observed changes, including long-term potentiation (LTP). Material and Methods: Female Wistar rats (35 days old; n = 102) were allocated into six groups: control (distilled water, v.o), ethanol (3 g/kg/day; 3 days on-4 days off, v.o) , caffeine (10 mg/kg/day, v.o), caffeine + ethanol, A2A antagonist SCH58261 (0.1 mg/kg/day, intraperitoneal - i,p) and ethanol + SCH58261. The animals were submitted to open field behavioral tests, object recognition and elevated plus maze. The oxidative biochemistry parameters of trolox equivalent antioxidant capacity (TEAC), glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), nitric oxide (NO), thiobarbituric acid reactive substances (TBARS) in the pre- frontal and hippocampus. LTP recordings in the medial prefrontal cortex (mPFC), ventral (vHip) and dorsal (dHIP) portions of the hippocampus of the control, ethanol, ethanol + SCH58261 and SCH58261 groups were evaluated through electrophysiology. Results: Caffeine prevented ethanol-induced behavioral impairments, including by blocking A2A receptors. In addition, it attenuated the oxidative stress induced by binge drinking by alternative A2A receptor pathways. Blockade of A2A receptors increased LTP levels in mPFC and vHIP, however decreased in dHIP. Conclusion: Caffeine showed neuroprotection in behavioral changes and oxidative stress induced by the binge drinking model in adolescent rats. In addition, blockade of A2A receptors mitigated the observed behavioral changes, with improvement of LTP levels in the prefrontal cortex and hippocampus, which suggests the contribution of this pathway to neuroprotection in deficits induced by ethanol exposure during adolescence.
Acesso aberto (Open Access)
O transportador XCG- medeia a captação de glutamato independente de sódio em cultura primária de células gliais da cóclea de camundongos neonatos
(Universidade Federal do Pará, 2022-10-20) MARTINS, Luana Carvalho; OLIVEIRA, Karen Renata Herculano Matos; http://lattes.cnpq.br/3032008039259369
The cochlea is a sensory organ of the auditory system whose excitatory synapses are mediated by L-Glutamate. Since glutamate has physiological and pathological repercussions on the cochlea, the crucial role of glutamate transport mechanisms capable of regulating the extracellular concentration of this neurotransmitter in order to maintain auditory function is highlighted. Within this context, in this study we sought to investigate the activity and expression of glutamate transport systems in an in vitro model of primary cultures of cochlear glial cells obtained from newborn mice of the Balb/C lineage. For this, we determined the sodium dependent and independent glutamate transport by means of glutamate uptake and release assays whose extracellular concentrations were quantified using High Performance Liquid Chromatography coupled to a fluorescence detector. Finally, the cells were subjected to immunofluorescence assay for XCG sodium-independent glutamate transporter labeling. In our results, we demonstrate that cochlear glial cells have a glutamate transport system mediated by the XCG- transporter. Such data suggest a possible role of this transporter in the control of extracellular concentrations of glutamate and regulation of the redox state, which may help to preserve auditory function.

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