Programa de Pós-Graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Universidade Federal de Pelotas, Pelotas, RS, 96010-900, Brazil.
Programa de Pós-Graduação em Química, Laboratório de Síntese Orgânica Limpa (LASOL), Universidade Federal de Pelotas, P.O. Box 354, Pelotas, RS, 96010-900, Brazil.
Mol Neurobiol. 2019 Sep;56(9):6398-6408. doi: 10.1007/s12035-019-1530-5. Epub 2019 Feb 25.
This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) to restore the cognitive impairment caused by aging in male Wistar rats. Moreover, modulation of neuroplasticity markers, acetylcholinesterase (AChE) activity, and cholesterol levels was performed. Aged rats were intragastrically treated with 4-PSQ (5 mg/kg) for 7 days. Animals were tested in behavioral tasks, and then plasma (to determine cholesterol levels), hippocampus, and cerebral cortex (to determine neural cell adhesion molecule (NCAM) and polysialyltransferase (PST) levels, and AChE activity) were removed. Our findings demonstrated that treatment of aged rats with 4-PSQ restored short-term and long-term memories in the object recognition tests. 4-PSQ treatment did not restore exploratory activity (rearings) but partially restored locomotor activity (crossings) reduced by aging in the open-field test. Moreover, the compound restored the reduction in the NCAM and PST levels, and AChE activity in cerebral structures, as well as the increase in the plasma cholesterol levels, caused by aging in rats. In conclusion, 4-PSQ restored cognitive impairment caused by aging in rats by modulating synaptic plasticity, cholinergic system, and cholesterol levels.
本研究探讨了 7-氯-4-(苯硒基)喹啉（4-PSQ）对雄性 Wistar 大鼠衰老引起的认知障碍的恢复作用。此外，还对神经可塑性标志物、乙酰胆碱酯酶（AChE）活性和胆固醇水平进行了调节。采用灌胃法给予老龄大鼠 4-PSQ（5mg/kg）7 天。动物在行为任务中进行测试，然后取出血浆（测定胆固醇水平）、海马体和大脑皮层（测定神经细胞黏附分子（NCAM）和多涎酸转移酶（PST）水平以及 AChE 活性）。研究结果表明，4-PSQ 治疗老龄大鼠可恢复其在物体识别测试中的短期和长期记忆。4-PSQ 治疗并未恢复老龄大鼠在旷场试验中因衰老而减少的探索性活动（后肢站立），但部分恢复了其运动活动（穿越）。此外，该化合物还恢复了因衰老导致的大脑结构中 NCAM 和 PST 水平以及 AChE 活性的降低，以及血浆胆固醇水平的升高。总之，4-PSQ 通过调节突触可塑性、胆碱能系统和胆固醇水平，恢复了衰老大鼠的认知障碍。
