Navegando por Autor "Souza, Diogo Onofre"
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Item Antidepressant-like effects of chronic guanosine in the olfactory bulbectomy mouse model.(2021) Almeida, Roberto Farina de; Souza, Diogo Onofre; Nonose, Yasmine; Ganzella, Marcelo; Loureiro, Samanta Oliveira; Rocha, Andréia; Machado, Daniele Guilhermano; Bellaver, Bruna; Fontella, Fernanda Urruth; Leffa, Douglas Teixeira; Pettenuzzo, Letícia Ferreira; Venturin, Gianina Teribele; Greggio, Samuel; Costa, Jaderson Costa da; Zimmer, Eduardo Rigon; Elisabetsky, ElaineMajor depressive disorder (MDD) leads to pervasive changes in the health of afflicted patients. Despite advances in the understanding of MDD and its treatment, profound innovation is needed to develop fast-onset antidepressants with higher effectiveness. When acutely administered, the endogenous nucleoside guanosine (GUO) shows fast- onset antidepressant-like effects in several mouse models, including the olfactory bulbectomy (OBX) rodent model. OBX is advocated to possess translational value and be suitable to assess the time course of depressive-like behavior in rodents. This study aimed at investigating the long-term behavioral and neurochemical effects of GUO in a mouse model of depression induced by bilateral bulbectomy (OBX). Mice were submitted to OBX and, after 14 days of recovery, received daily (ip) administration of 7.5 mg/kg GUO or 40 mg/kg imipramine (IMI) for 45 days. GUO and IMI reversed the OBX-induced hyperlocomotion and recognition memory impairment, hippocampal BDNF increase, and redox imbalance (ROS, NO, and GSH levels). GUO also mitigated the OBX-induced hippocampal neuroinflammation (IL-1, IL-6, TNF-α, INF-γ, and IL-10). Brain microPET imaging ([18F]FDG) shows that GUO also prevented the OBX-induced increase in hippocampal FDG metabolism. These results provide additional evidence for GUO antidepressant-like effects, associated with beneficial neurochemical outcomes relevant to counteract depression.Item Dynamics and immunomodulation of cognitive deficits and behavioral changes in non-severe experimental malaria.(2022) Gonçalves, Pamela Rosa; Sousa, Luciana Pereira de; Maia, Aline Barbosa; Gomes, Flávia Lima Ribeiro; Gress, Caroline Cristhiani Tavares de Lima; Werneck, Guilherme Loureiro; Souza, Diogo Onofre; Almeida, Roberto Farina de; Ribeiro, Cláudio Tadeu DanielData recently reported by our group indicate that stimulation with a pool of immunogens capable of eliciting type 2 immune responses can restore the cognitive and behavioral dysfunctions recorded after a single episode of nonsevere rodent malaria caused by Plasmodium berghei ANKA. Here we explored the hypothesis that isolated immunization with one of the type 2 immune response-inducing immunogens, the human diphtheria-tetanus (dT) vaccine, may revert damages associated with malaria. To investigate this possibility, we studied the dynamics of cognitive deficits and anxiety-like phenotype following non-severe experimental malaria and evaluated the effects of immunization with both dT and of a pool of type 2 immune stimuli in reversing these impairments. Locomotor activity and long-term memory deficits were assessed through the open field test (OFT) and novel object recognition task (NORT), while the anxiety-like phenotype was assessed by OFT and light/dark task (LDT). Our results indicate that poor performance in cognitive-behavioral tests can be detected as early as the 12th day after the end of antimalarial treatment with chloroquine and may persist for up to 155 days post infection. The single immunization strategy with the human dT vaccine showed promise in reversal of long-term memory deficits in NORT, and anxiety-like behavior in OFT and LDT.Item Effects of intranasal guanosine administration on brain function in a rat model of ischemic stroke.(2021) Müller, Gabriel Cardozo; Loureiro, Samanta Oliveira; Pettenuzzo, Letícia Ferreira; Almeida, Roberto Farina de; Ynumaru, Evandro Yukio; Guazzelli, Pedro Arend; Meyer, Fabíola Schons; Pasquetti, Mayara Vendramin; Castro, Marcelo Ganzela Martins de; Calcagnotto, Maria Elisa; Souza, Diogo OnofreIschemic stroke is a major cause of morbidity and mortality worldwide and only few affected patients are able to receive treatment, especially in developing countries. Detailed pathophysiology of brain ischemia has been extensively studied in order to discover new treatments with a broad therapeutic window and that are accessible to patients worldwide. The nucleoside guanosine (Guo) has been shown to have neuroprotective effects in animal models of brain diseases, including ischemic stroke. In a rat model of focal permanent ischemia, systemic administration of Guo was effective only when administered immediately after stroke induction. In contrast, intranasal administration of Guo (In-Guo) was effective even when the first administration was 3 h after stroke induction. In order to validate the neuroprotective effect in this larger time window and to investigate In-Guo neuroprotection under global brain dysfunction induced by ischemia, we used the model of thermocoagulation of pial vessels in Wistar rats. In our study, we have found that In-Guo administered 3 h after stroke was capable of preventing ischemia-induced dysfunction, such as bilateral suppression and synchronicity of brain oscillations and ipsilateral cell death signaling, and increased permeability of the blood-brain barrier. In addition, In-Guo had a long-lasting effect on preventing ischemia-induced motor impairment. Our data reinforce In-Guo adminis- tration as a potential new treatment for brain ischemia with a more suitable therapeutic window.Item Guanosine fast onset antidepressant-like efects in the olfactory bulbectomy mice model.(2020) Almeida, Roberto Farina de; Pocharski, Camila Barbosa; Rodrigues, Ana Lúcia Severo; Elisabetsky, Elaine; Souza, Diogo OnofreItem Immune system challenge improves recognition memory and reverses malaria‐induced cognitive impairment in mice.(2021) Sousa, Luciana Pereira de; Gomes, Flávia Lima Ribeiro; Almeida, Roberto Farina de; Souza, Tadeu Mello e; Werneck, Guilherme Loureiro; Souza, Diogo Onofre; Ribeiro, Cláudio Tadeu DanielThe immune system plays a role in the maintenance of healthy neurocognitive function. Diferent patterns of immune response triggered by distinct stimuli may afect nervous functions through regulatory or deregulatory signals, depending on the properties of the exogenous immunogens. Here, we investigate the efect of immune stimulation on cognitive-behavioural parameters in healthy mice and its impact on cognitive sequelae resulting from non-severe experimental malaria. We show that immune modulation induced by a specifc combination of immune stimuli that induce a type 2 immune response can enhance long-term recognition memory in healthy adult mice subjected to novel object recognition task (NORT) and reverse a lack of recognition ability in NORT and anxiety-like behaviour in a light/dark task that result from a single episode of mild Plasmodium berghei ANKA malaria. Our fndings suggest a potential use of immunogens for boosting and recovering recognition memory that may be impaired by chronic and infectious diseases and by the efects of ageing.Item Low-cost apparatus for cigarette smoke exposure in rats.(2022) Müller, Gabriel Cardozo; Loureiro, Samanta Oliveira; Pettenuzzo, Letícia Ferreira; Almeida, Roberto Farina de; Ynumaru, Evandro Yukio; Guazzelli, Pedro Arend; Meyer, Fabíola Schons; Pasquetti, Mayara Vendramin; Castro, Marcelo Ganzela Martins de; Calcagnotto, Maria Elisa; Souza, Diogo OnofreIschemic stroke is a major cause of morbidity and mortality worldwide and only few affected patients are able to receive treatment, especially in developing countries. Detailed pathophysiology of brain ischemia has been extensively studied in order to discover new treatments with a broad therapeutic window and that are accessible to patients worldwide. The nucleoside guanosine (Guo) has been shown to have neuroprotective effects in animal models of brain diseases, including ischemic stroke. In a rat model of focal permanent ischemia, systemic administration of Guo was effective only when administered immediately after stroke induction. In contrast, intranasal administration of Guo (In-Guo) was effective even when the first administration was 3 h after stroke induction. In order to validate the neuroprotective effect in this larger time window and to investigate In-Guo neuroprotection under global brain dysfunction induced by ischemia, we used the model of thermocoagulation of pial vessels in Wistar rats. In our study, we have found that In-Guo administered 3 h after stroke was capable of preventing ischemia-induced dysfunction, such as bilateral suppression and synchronicity of brain oscillations and ipsilateral cell death signaling, and increased permeability of the blood-brain barrier. In addition, In-Guo had a long-lasting effect on preventing ischemia-induced motor impairment. Our data reinforce In-Guo adminis- tration as a potential new treatment for brain ischemia with a more suitable therapeutic window.Item Post-weaning social isolation impairs purinergic signaling in rat brain.(2021) Andrejew, Roberta; Paim, Milla; Moritz, Cesar Eduardo Jacintho; Carreño, Fernando; Rates, Stela Maris Kuze; Elisabetsky, Elaine; Souza, Diogo Onofre; Almeida, Roberto Farina de; Battastini, Maria OliveiraEarly life stressors, such as social isolation (SI), can disrupt brain development contributing to behavioral and neurochemical alterations in adulthood. Purinergic receptors and ectonucleotidases are key regulators of brain development in embryonic and postnatal periods, and they are involved in several psychiatric disorders, including schizophrenia. The extracellular ATP drives purinergic signaling by activating P2X and P2Y receptors and it is hydrolyzed by ectonucleotidases in adenosine, which activates P1 receptors. The purpose of this study was to investigate if SI, a rodent model used to replicate abnormal behavior relevant to schizophrenia, impacts purinergic signaling. Male Wistar rats were reared from weaning in group-housed or SI conditions for 8 weeks. SI rats exhibited impairment in prepulse inhibition and social interaction. SI presented increased ADP levels in cerebrospinal fluid and ADP hydrolysis in the hippocampus and striatum synaptosomes. Purinergic receptor expressions were upregulated in the prefrontal cortex and downregulated in the hippocampus and striatum. A2A receptors were differentially expressed in SI prefrontal cortex and the striatum, suggesting distinct roles in these brain structures. SI also presented decreased ADP, adenosine, and guanosine levels in the cerebrospinal fluid in response to D-amphetamine. Like patients with schizophrenia, uric acid levels were prominently increased in SI rats after D-amphetamine challenge. We suggest that the SI-induced deficits in prepulse inhibition might be related to the SI-induced changes in purinergic signaling. We provide new evidence that purinergic signaling is markedly affected in a rat model relevant to schizophrenia, pointing out the importance of purinergic system in psychiatry conditions.