Mozafari Nazanin, Shamsizadeh Ali, Fatemi Iman, Allahtavakoli Mohammad, Moghadam-Ahmadi Amir, Kaviani Elham, Kaeidi Ayat
Physiology-Pharmacology Research Center, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Department of Physiology and Pharmacology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
Iran J Basic Med Sci. 2018 Jul;21(7):724-730. doi: 10.22038/IJBMS.2018.28544.6934.
Growing evidence suggests that dysfunction of the glutamatergic system and α-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) receptors are involved in pathology of Alzheimer's disease (AD). Because AMPA receptors play a key role in plasticity synaptic regulation, positive modulation of these receptors may rescue the cognitive deficits in the AD. The aim of this study was to explore the effect of CX691, a specific positive allosteric modulator of the AMPA-type glutamate receptors (Ampakine), on spatial learning and memory in a rat model of AD.
For induction of AD, amyloid-beta 1-42 (Aβ1-42) was microinjected into the hippocampus of male Wistar rats (250-300 g). The Morris water maze (MWM) test was used to evaluate the effect of CX691 (0.03 and 0.3 mg/kg, twice a day for 10 days, orally) on spatial learning and memory of rats. In order to evaluate the protein expression of brain-derived neurotrophic factor (BDNF) in hippocampus tissue, ELISA test was used.
The obtained data showed that treatment with CX691 (0.3 mg/kg) improves the impairment of spatial learning and memory in AD rats. Also, treatment with CX691 (0.3 mg/kg), increased the BDNF protein level in hippocampus tissue of AD rats compared to non-treated animals.
The CX691 can improve the BDNF protein expression as well as spatial performance of learning and memory in AD rats.
越来越多的证据表明，谷氨酸能系统功能障碍和α-氨基-3-羟基-5-甲基-4-异唑丙酸（AMPA）受体参与了阿尔茨海默病（AD）的病理过程。由于AMPA受体在突触可塑性调节中起关键作用，对这些受体的正向调节可能挽救AD患者的认知缺陷。本研究旨在探讨AMPA型谷氨酸受体的特异性正向变构调节剂CX691（一种安帕金）对AD大鼠模型空间学习和记忆的影响。
为诱导AD，将淀粉样β蛋白1-42（Aβ1-42）微量注射到雄性Wistar大鼠（250-300 g）的海马中。采用莫里斯水迷宫（MWM）试验评估CX691（0.03和0.3 mg/kg，每天口服两次，共10天）对大鼠空间学习和记忆的影响。为评估海马组织中脑源性神经营养因子（BDNF）的蛋白表达，采用酶联免疫吸附测定（ELISA）试验。
所得数据表明，CX691（0.3 mg/kg）治疗可改善AD大鼠的空间学习和记忆障碍。此外，与未治疗动物相比，CX691（0.3 mg/kg）治疗可提高AD大鼠海马组织中的BDNF蛋白水平。
CX691可改善AD大鼠的BDNF蛋白表达以及学习和记忆的空间表现。
