Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania |
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| Institution: | 1. Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil;2. Laboratory of Genetic Identification and Medical Genetic Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil;3. INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil;4. Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA;5. Laboratory of Neurosciences, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, 88806-000, Criciúma, Santa Catarina, Brazil;6. Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-903, Rio Grande do Sul, Brazil;7. Department of Psychiatry, Universidade Federal Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil;1. Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Medical School at Houston, Houston, TX, USA;2. Laboratory of Neurosciences, Graduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, Criciúma, SC, Brazil;3. Graduate Program in Health and Behavior, Catholic University of Pelotas, Pelotas, RS, Brazil;4. Department of Clinical Medicine and Translational Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil;5. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA;1. University of South Carolina School of Medicine, Columbia, SC 29209, USA;2. Pfizer, Neuroscience, Groton, CT 06340, USA |
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| Abstract: | Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. |
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| Keywords: | Amphetamine Bipolar disorder Memory BDNF Animal model Mania |
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