Zhang, Lijun Seo, Jae Hong Li, Huan Nam, Ghilsoo Yang, Hyun Ok 2024-01-19T22:04:01Z 2024-01-19T22:04:01Z 2021-09-03 2018-08 0007-1188 https://pubs.kist.re.kr/handle/201004/121103 BACKGROUND AND PURPOSE Inhibition of PDE5 improves synaptic plasticity and memory via enhancing cGMP expression, thus activating the cGMP/cAMP response element binding protein (CREB) signalling pathway. This study investigated the effects of a PDE5 inhibitor on scopolamine-induced cognitive dysfunction, using memory-related behavioural tests and biochemical assays. EXPERIMENTAL APPROACH In mice were pretreated with PDE5 inhibitor, amnesia was induced by scopolamine. The learning and memory abilities of mice were tested using the Morris water maze test, the Y-maze test, the passive avoidance test and the novel object recognition test in sequence. Expression of memory-related bio-molecules and oxidative stress parameters in brain tissue were measured using Western blot and spectrophotometry respectively. KEY RESULTS KJH-1002, a novel and potent inhibitor of PDE5 (IC50 0.059 +/- 0.04 nmol.L-1), was synthesized. In the behavioural tests, it markedly improved the memory performance impaired by scopolamine, indicating a restoration of cognitive function in the mice. Moreover, KJH-1002 increased cGMP levels in the cortex and the scopolamine-reduced expression of phosphorylated CREB, Levels of ERK 1/2, Akt and brain-derived neurotrophic factor in the cortex and hippocampus were restored by KJH-1002 treatment. In addition, KJH-1002 administration increased the activities of SOD, glutathione peroxidase and glutathione reductase, and decreased the level of malondialdehyde. CONCLUSION AND IMPLICATIONS KJH-1002 restored cognitive function in scopolamine-induced amnesia mice by activating the cGMP/CREB signalling pathway and attenuating oxidative stress. The beneficial effects of KJH-1002 on cognition indicate its potential as a therapeutic candidate for Alzheimer's disease. English WILEY INDUCED COGNITIVE DYSFUNCTION OBJECT RECOGNITION MEMORY ALZHEIMERS-DISEASE SYNAPTIC PLASTICITY IN-VIVO ACETYLCHOLINESTERASE INHIBITORS NEUROTROPHIC FACTOR CONCISE GUIDE RAT-BRAIN SILDENAFIL The phosphodiesterase 5 inhibitor, KJH-1002, reverses a mouse model of amnesia by activating a cGMP/cAMP response element binding protein pathway and decreasing oxidative damage Article 10.1111/bph.14377 1 BRITISH JOURNAL OF PHARMACOLOGY, v.175, no.16, pp.3347 - 3360 BRITISH JOURNAL OF PHARMACOLOGY 175 16 3347 3360 scie scopus 000439750500014 2-s2.0-85050471772 Pharmacology & Pharmacy Pharmacology & Pharmacy Article INDUCED COGNITIVE DYSFUNCTION OBJECT RECOGNITION MEMORY ALZHEIMERS-DISEASE SYNAPTIC PLASTICITY IN-VIVO ACETYLCHOLINESTERASE INHIBITORS NEUROTROPHIC FACTOR CONCISE GUIDE RAT-BRAIN SILDENAFIL