β-Asarone Rescues Pb-Induced Impairments of Spatial Memory and Synaptogenesis in Rats

• Published in: PloS one Vol. 11; no. 12; p. e0167401
• Main Authors: Yang, Qian-Qian, Xue, Wei-Zhen, Zou, Rong-Xin, Xu, Yi, Du, Yang, Wang, Shuang, Xu, Lai, Chen, Yuan-Zhi, Wang, Hui-Li, Chen, Xiang-Tao
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.12.2016; Public Library of Science (PLoS)
• Subjects: Acorus; Acorus - chemistry; Alzheimer's disease; Animal cognition; Animals; Anisoles - chemistry; Anisoles - pharmacokinetics; Anisoles - therapeutic use; ARC protein; Asarones; Biology and Life Sciences; Blood-brain barrier; Brain; Chromatography; Cognitive ability; Cytoskeleton; Dentate gyrus; Drinking water; Exposure; Female; Gene expression; Glutamic acid receptors (ionotropic); High performance liquid chromatography; Hippocampus; Hippocampus - cytology; Hippocampus - drug effects; Hippocampus - physiopathology; Kinases; Laboratory animals; Lactation; Lead; Lead - toxicity; Learning; Liquid chromatography; Male; Maze Learning - drug effects; Medical research; Medicine and Health Sciences; Memory; Memory Disorders - chemically induced; Memory Disorders - drug therapy; Memory Disorders - physiopathology; Memory tasks; N-Methyl-D-aspartic acid receptors; Nervous system; Neurogenesis; Neurogenesis - drug effects; Neuroprotection; Neuroprotective Agents - chemistry; Neuroprotective Agents - pharmacokinetics; Neuroprotective Agents - therapeutic use; Rats; Rats, Sprague-Dawley; Research and Analysis Methods; Rodents; Spatial analysis; Spatial memory; Spatial Memory - drug effects; Spine; Synapses - drug effects; Synapses - pathology; Synaptogenesis; Test procedures; Wnt protein; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0167401

Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of β-asarone, an active component from Chinese Herbs Acorus tatarinowii Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and β-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21. Also, the adult rats were exposed to Pb from embryo stage to 11 weeks old and β-asarone (2.5, 10, 40mg kg-1, respectively) was given from 9 to 11 weeks old. The level of β-asarone in brain tissue was measured by High Performance Liquid Chromatography. The Morris water maze test and Golgi-Cox staining method were used to assess spatial memory ability and synaptogenesis. The protein expression of NR2B subunit of NMDA receptor, Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and Wnt family member 7A (Wnt7a) in hippocampus, as well as mRNA expression of Arc/Arg3.1 and Wnt7a, was also explored. We found that β-asarone could pass through the blood brain barrier quickly. And β-asarone effectively attenuated Pb-induced reduction of spine density in hippocampal CA1 and dentate gyrus areas in a dose-dependent manner both in developmental and adult rats, meanwhile the Pb-induced impairments of learning and memory were partially rescued. In addition, β-asarone effectively up-regulated the protein expression of NR2B, Arc and Wnt7a, as well as the mRNA levels of Arc/Arg3.1 and Wnt7a, which had been suppressed by Pb exposure. The results suggest the neuroprotective properties of β-asarone against Pb-induced memory impairments, and the effect is possibly through the regulation of synaptogenesis, which is mediated via Arc/Arg3.1 and Wnt pathway.