Navegando por Autor "Elisabetsky, Elaine"

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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, Elaine
Major 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.
Guanine-based purines as an innovative target to treat major depressive disorder.
(2021) Almeida, Roberto Farina de; Ferreira, Tiago Pedrosa; David, Camila Vieira Chagas; Silva, Paulo Correa de Abreu e; Santos, Sulamita Aparecida Ambrosia dos; Rodrigues, Ana Lúcia Severo; Elisabetsky, Elaine
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 Onofre
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 Oliveira
Early 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.