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.
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.
Psychopharmacology (Berl). 2021 Jul;238(7):1937-1951. doi: 10.1007/s00213-021-05821-y. Epub 2021 Mar 19.
Obesity is considered one of the major global health problems and increases the risk of several medical complications, such as diabetes and mental illnesses.
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.
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.
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.
In brief, 4-PSQ therapy improved hypothalamic obesity-related parameters, as well as psychiatric symptoms, cognitive impairment, and neurochemical alterations found in obese rats.
肥胖被认为是全球主要的健康问题之一，会增加患多种医学并发症的风险，如糖尿病和精神疾病。
本研究旨在探讨 7-氯-4-（苯基硒基）喹啉（4-PSQ）对下丘脑肥胖大鼠肥胖参数、行为和神经化学改变的影响。
雄性 Wistar 大鼠接受皮下新生注射谷氨酸单钠（MSG，4g/kg）或生理盐水。在 Lee 指数评估后，大鼠被分为几组，每天一次用 4-PSQ（5mg/kg，灌胃）或菜籽油（产后第 60→76 天）治疗。从产后第 66 天到第 74 天进行旷场、高架十字迷宫、强迫游泳、物体识别/位置记忆和跳下抑制回避任务。产后第 76 天，大鼠被安乐死，取出附睾脂肪、血液、大脑皮质和海马。检测血液生化参数以及皮质/海马乙酰胆碱酯酶（AChE）和 Na+/K+-ATP 酶活性。
MSG 增加了 Lee 指数，表征了化学诱导的下丘脑肥胖模型。4-PSQ 逆转了 MSG 暴露引起的附睾脂肪、血糖和甘油三酯水平的增加。4-PSQ 减轻了新生注射 MSG 引起的焦虑样和抑郁样行为。4-PSQ 治疗逆转了 MSG 肥胖大鼠的记忆缺陷。MSG 引起的神经化学改变，表现为大鼠大脑皮质和海马中 Na+/K+-ATP 酶和 AChE 活性的刺激，被 4-PSQ 治疗所纠正。
总之，4-PSQ 治疗改善了与下丘脑肥胖相关的参数，以及肥胖大鼠的精神症状、认知障碍和神经化学改变。
