Programa de Pós-Graduação Em Bioquímica E Bioprospecção (PPGBBio), Laboratório de Pesquisa Em Farmacologia Bioquímica (LaFarBio), Centro de Ciências Químicas, Farmacêuticas E de Alimentos, Universidade Federal de Pelotas, Pelotas, RS, CEP 96010-900, Brazil.
Laboratório de Genômica Estrutural, Programa de Pós-Graduação Em Biotecnologia, Universidade Federal de Pelotas, Pelotas, RS, Brazil.
Psychopharmacology (Berl). 2022 Jan;239(1):59-81. doi: 10.1007/s00213-021-06039-8. Epub 2022 Jan 11.
Depression is often associated with memory impairment, a clinical feature of Alzheimer's disease (AD), but no effective treatment is available. 7-Chloro-4-(phenylselanyl) quinoline (4-PSQ) has been studied in experimental models of diseases that affect the central nervous system.
The pharmacological activity of 4-PSQ in depressive-like behavior associated with memory impairment induced by acute restraint stress (ARS) in male Swiss mice was evaluated.
ARS is an unavoidable stress model that was applied for a period of 240 min. Ten minutes after ARS, animals were intragastrically treated with canola oil (10 ml/kg) or 4-PSQ (10 mg/kg) or positive controls (paroxetine or donepezil) (10 mg/kg). Then, after 30 min, mice were submitted to behavioral tests. Corticosterone levels were evaluated in plasma and oxidative stress parameters; monoamine oxidase (MAO)-A and MAO -B isoform activity; mRNA expression levels of kappa nuclear factor B (NF-κB); interleukin (IL)-1β, IL-18, and IL-33; phosphatidylinositol-se-kinase (PI3K); protein kinase B (AKT2), as well as acetylcholinesterase activity were evaluated in the prefrontal cortex and hippocampus.
4-PSQ attenuated the depressive-like behavior, self-care, and memory impairment caused by ARS. Based on the evidence, we believe that effects of 4-PSQ may be associated, at least in part, with the attenuation of HPA axis activation, attenuation of alterations in the monoaminergic system, modulation of oxidative stress, reestablishment of AChE activity, modulation of the PI3K/AKT2 pathway, and reduction of neuroinflammation.
These results suggested that 4-PSQ exhibited an antidepressant-like effect and attenuated the memory impairment induced by ARS, and it is a promising molecule to treat these comorbidities.
抑郁症常伴有记忆障碍，这是阿尔茨海默病（AD）的一个临床特征，但目前尚无有效的治疗方法。7-氯-4-（苯硒基）喹啉（4-PSQ）已在影响中枢神经系统的疾病的实验模型中进行了研究。
评估 4-PSQ 对急性束缚应激（ARS）诱导的雄性瑞士小鼠抑郁样行为和记忆障碍的药理学活性。
ARS 是一种不可避免的应激模型，持续 240 分钟。ARS 结束后 10 分钟，动物经胃内给予菜籽油（10ml/kg）或 4-PSQ（10mg/kg）或阳性对照物（帕罗西汀或多奈哌齐）（10mg/kg）。30 分钟后，对小鼠进行行为测试。评估血浆中环皮质酮水平和氧化应激参数；单胺氧化酶（MAO）-A 和 MAO-B 同工酶活性；κ 核因子 B（NF-κB）的 mRNA 表达水平；白细胞介素（IL）-1β、IL-18 和 IL-33；磷酸肌醇-3-激酶（PI3K）；蛋白激酶 B（AKT2）以及前额叶皮层和海马中的乙酰胆碱酯酶活性。
4-PSQ 减轻了 ARS 引起的抑郁样行为、自我护理和记忆障碍。基于这些证据，我们认为 4-PSQ 的作用可能至少部分与 HPA 轴激活的减弱、单胺能系统改变的减弱、氧化应激的调节、AChE 活性的恢复、PI3K/AKT2 通路的调节以及神经炎症的减轻有关。
这些结果表明，4-PSQ 表现出抗抑郁样作用，并减轻了 ARS 诱导的记忆障碍，是治疗这些共病的有前途的分子。
