PMID- 31632240 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20200930 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 13 DP - 2019 TI - Phosphodiesterase-2 Inhibitor Bay 60-7550 Ameliorates Abeta-Induced Cognitive and Memory Impairment via Regulation of the HPA Axis. PG - 432 LID - 10.3389/fncel.2019.00432 [doi] LID - 432 AB - The dysfunction of the hypothalamus-pituitary-adrenal (HPA) axis is often seen in Alzheimer's disease (AD) patients with cognitive deficits. Selective inhibition of phosphodiesterase (PDE) 4 and 5 has already proven to be effective in reducing beta-amyloid 1-42 (Abeta1-42)-mediated pathology by regulating corticotropin-releasing factor (CRF) and glucocorticoid receptor (GR) expression, suggesting that PDE-dependent signaling is involved in Abeta1-42-induced HPA axis dysfunction. However, nausea and vomiting are the side effects of some PDE4 inhibitors, which turn our attention to other PDEs. PDE2 are highly expressed in the hippocampus and cortex, which associate with learning and memory, but not in the area postrema that would cause vomiting. The present study suggested that microinjection of Abeta1-42 to the intracerebroventricle induced learning and memory impairments and dysregulation of the HPA axis by increased expression of CRF and GR. However, the PDE2 inhibitor Bay 60-7550 significantly ameliorated the learning and memory impairment in the Morris water maze (MWM) and step-down passive avoidance tests. The Abeta1-42-induced increased CRF and GR levels were also reversed by the treatment with Bay 60-7550. These Bay 60-7550's effects were prevented by pretreatment with the PKG inhibitor KT5823. Moreover, the Bay 60-7550-induced downstream phosphorylation of cyclic AMP response element binding (pCREB) and brain-derived neurotrophic factor (BDNF) expression was also prevented (or partially prevented) by KT5823 or the PKA inhibitor H89. These results may lead to the discovery of novel strategies for the treatment of age-related cognitive disorders, such as AD, which affects approximately 44 million people worldwide. CI - Copyright (c) 2019 Ruan, Du, Tao, Shan, Ye, Tang, Pan, Lv, Zhang and Pan. FAU - Ruan, Lina AU - Ruan L AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Du, Kai AU - Du K AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Tao, Mengjia AU - Tao M AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Shan, Chunyan AU - Shan C AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Ye, Ruixuan AU - Ye R AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Tang, Yali AU - Tang Y AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. FAU - Pan, Hanbo AU - Pan H AD - Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China. FAU - Lv, Jinpeng AU - Lv J AD - College of Pharmaceutical Engineering and Life Sciences, Changzhou University, Changzhou, China. FAU - Zhang, Meixi AU - Zhang M AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. AD - Pingyang County Hospital of Traditional Chinese Medicine, Pingyang County, China. FAU - Pan, Jianchun AU - Pan J AD - Brain Institute, School of Pharmacy, Wenzhou Medical University, Wenzhou, China. LA - eng PT - Journal Article DEP - 20191002 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC6783519 OTO - NOTNLM OT - BDNF OT - Bay 60-7550 OT - beta amyloid 1-42 OT - hypothalamus-pituitary-adrenal axis OT - pCREB OT - phosphodiesterase 2 EDAT- 2019/10/22 06:00 MHDA- 2019/10/22 06:01 PMCR- 2019/01/01 CRDT- 2019/10/22 06:00 PHST- 2019/07/02 00:00 [received] PHST- 2019/09/09 00:00 [accepted] PHST- 2019/10/22 06:00 [entrez] PHST- 2019/10/22 06:00 [pubmed] PHST- 2019/10/22 06:01 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2019.00432 [doi] PST - epublish SO - Front Cell Neurosci. 2019 Oct 2;13:432. doi: 10.3389/fncel.2019.00432. eCollection 2019.