PMID- 35276121 OWN - NLM STAT- MEDLINE DCOM- 20220502 LR - 20220502 IS - 1873-507X (Electronic) IS - 0031-9384 (Linking) VI - 249 DP - 2022 May 15 TI - Floralozone improves cognitive impairment in vascular dementia rats via regulation of TRPM2 and NMDAR signaling pathway. PG - 113777 LID - S0031-9384(22)00084-1 [pii] LID - 10.1016/j.physbeh.2022.113777 [doi] AB - Vascular dementia (VD) is the second largest type of dementia after Alzheimer's disease. At present, the pathogenesis is complex and there is no effective treatment. Floralozone has been shown to reduce atherosclerosis in rats caused by a high-fat diet. However, whether it plays a role in VD remains elusive. In the present study, the protective activities and relevant mechanisms of Floralozone were evaluated in rats with cognitive impairment, which were induced by bilateral occlusion of the common carotid arteries (BCCAO) in rats. Cognitive function, pathological changes and oxidative stress condition in the brains of VD rats were assessed using Neurobehavioral tests, Morris water maze tests, hematoxylin-eosin staining, Neu N staining, TUNEL staining, Golgi staining, Western blot assay and antioxidant assays (MDA, SOD, GSH), respectively. The results indicated that VD model was established successfully and BCCAO caused a decline in spatial learning and memory and hippocampal histopathological abnormalities of rats. Floralozone (50, 100, 150 mg/kg) dose-dependently alleviated the pathological changes, decreased oxidative stress injury, which eventually reduced cognitive impairment in BCCAO rats. The same results were shown in further experiments with neurobehavioral tests. At the molecular biological level, Floralozone decreased the protein level of transient receptor potential melastatin-related 2 (TRPM2) in VD and normal rats, and increased the protein level of NR2B in hippocampus of N-methyl-D-aspartate receptor (NMDAR). Notably, Floralozone could markedly improved learning and memory function of BCCAO rats in Morris water maze (MWM) and improved neuronal cell loss, synaptic structural plasticity. In conclusion, Floralozone has therapeutic potential for VD, increased synaptic structural plasticity and alleviating neuronal cell apoptosis, which may be related to the TRPM2/NMDAR pathway. CI - Copyright (c) 2022 Elsevier Inc. All rights reserved. FAU - Yin, Ya-Ling AU - Yin YL AD - School of Basic Medical Sciences, Department of Physiology and Pathophysiology, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University,Xinxiang, China, 453003; College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: hnpdsyyl@163.com. FAU - Liu, Yan-Hua AU - Liu YH AD - College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: 601338346@qq.com. FAU - Zhu, Mo-Li AU - Zhu ML AD - College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: zhumoli2006@163.com. FAU - Wang, Huan-Huan AU - Wang HH AD - College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: 2903653579@qq.com. FAU - Qiu, Yue AU - Qiu Y AD - College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: 1412402925@qq.com. FAU - Wan, Guang-Rui AU - Wan GR AD - College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: wgrxxmu@163.com. FAU - Li, Peng AU - Li P AD - School of Basic Medical Sciences, Department of Physiology and Pathophysiology, Sino-UK Joint Laboratory of Brain Function and Injury and Department of Physiology and Neurobiology, Xinxiang Medical University,Xinxiang, China, 453003; College of Pharmacy, Henan international joint laboratory of cardiovascular remodeling and drug intervention, Xinxiang key laboratory of vascular remodeling intervention and molecular targeted therapy drug development, Xinxiang Medical University,Xinxiang, China, 453003. Electronic address: 071021@xxmu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220308 PL - United States TA - Physiol Behav JT - Physiology & behavior JID - 0151504 RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (TRPM Cation Channels) RN - 0 (Trpm2 protein, rat) SB - IM MH - Animals MH - *Cognitive Dysfunction/drug therapy/etiology MH - *Dementia, Vascular/complications/drug therapy MH - Disease Models, Animal MH - Hippocampus/metabolism MH - Maze Learning MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/metabolism MH - Signal Transduction MH - *TRPM Cation Channels/metabolism OTO - NOTNLM OT - Cognitive impairment OT - Floralozone OT - NMDA OT - TRPM2 OT - Vascular dementia EDAT- 2022/03/12 06:00 MHDA- 2022/05/03 06:00 CRDT- 2022/03/11 20:10 PHST- 2021/10/15 00:00 [received] PHST- 2022/02/23 00:00 [revised] PHST- 2022/03/07 00:00 [accepted] PHST- 2022/03/12 06:00 [pubmed] PHST- 2022/05/03 06:00 [medline] PHST- 2022/03/11 20:10 [entrez] AID - S0031-9384(22)00084-1 [pii] AID - 10.1016/j.physbeh.2022.113777 [doi] PST - ppublish SO - Physiol Behav. 2022 May 15;249:113777. doi: 10.1016/j.physbeh.2022.113777. Epub 2022 Mar 8.