Ethel Antunes Wilhelm1, Cristiane Luchese2, Karline C Rodrigues3, Cristiani F Bortolatto4, Ketlyn P da Motta3, Renata L de Oliveira3, Jaini J Paltian3, Roberta Krüger5, Silvane S Roman6, Silvana P Boeira7, Diego Alves5. 1. Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, Pelotas, RS, CEP 96010-900, Brazil. ethelwilhelm@yahoo.com. 2. Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, Pelotas, RS, CEP 96010-900, Brazil. cristiane_luchese@yahoo.com. 3. Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Campus Capão do Leão, Pelotas, RS, CEP 96010-900, Brazil. 4. Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Pelotas, RS, CEP 96010-900, Brazil. 5. Programa de Pós-graduação em Química, Laboratório de Síntese Orgânica Limpa - LASOL, Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), P.O. Box 354, Pelotas, RS, 96010-900, Brazil. 6. Universidade Regional Integrada, Campus Erechim, Erechim, RS, CEP 99700-000, Brazil. 7. Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Itaqui, RS, CEP 97650-000, Brazil.
Abstract
RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obese rats. METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. RESULTS: MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obese rats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.
RATIONALE: Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses. OBJECTIVE: The present study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) on obesity parameters, behavioral and neurochemical alterations in hypothalamic obeserats. METHODS: Male Wistar rats received subcutaneous neonatal injections of monosodium glutamate (MSG, 4g/kg) or saline. After the Lee Index evaluation, rats were divided into groups and treated with 4-PSQ (5 mg/kg, intragastric route) or canola oil once a day (post-natal days (PND) 60→76). Open-field, elevated plus-maze, forced swim task, object recognition/location memory, and stepdown inhibitory avoidance tasks were conducted from PND 66 to 74. On PND 76, rats were euthanized and epididymal fat, blood, cerebral cortex, andhippocampus were removed. Blood biochemical parameters and cortical/hippocampal acetylcholinesterase (AChE) and Na /K -ATPase activities were assessed. RESULTS:MSG increased the Lee Index characterizing the chemically induced hypothalamic obesity model. 4-PSQ reversed the increases of epididymal fat, blood glucose, and triglyceride levels caused by MSG exposure. 4-PSQ attenuated anxiety-like and depression-like behaviors induced by neonatal administrations of MSG. Memory deficits found in MSG-obeserats were reversed by treatment with 4-PSQ. Neurochemical alterations produced by MSG evidenced by stimulation ofNa+/K+-ATPase and AChE activities in the cerebral cortex and hippocampus of rats were normalized by 4-PSQ treatment. CONCLUSIONS: In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obeserats.
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