Schisantherin B ameliorates Aβ1-42-induced cognitive decline via restoration of GLT-1 in a mouse model of Alzheimer's disease.

Abstract

Accumulation of amyloid beta (Aβ) peptide and hyperphosphorylated tau protein has been proposed to play roles in neural destruction which induce Alzheimer's disease (AD) progresses, glutamate transporter type 1 (GLT-1) and Glycogen synthase kinase3β (GSK3β) may be the pathological links between Aβ and tau pathology. Schisantherin B (STB) is one bioactive of lignans isolated from Schisandra chinensis (Turcz.) Baill which has been commonly used as a traditional herbal medicine for thousands of years. This paper was designed to investigate the effects of STB on improving the cognitive function and neurodegeneration in the mouse model of Alzheimer's disease induced by Aβ1-42, and its possible mechanism were Glutamate transporter GLT-1, tau and GSK3β. It was found that successive intracerebroventricular (ICV) administration of STB (0.15mg/kg) for 5days significantly attenuated Aβ1-42-induced learning and memory impairment as measured by the Locomotor activity test, Y-maze test and Morris water maze test. Furthermore, STB at a dose of 0.15mg/kg restored the activities of GLT-1 and GSK3β while decreasing the levels of hyperphosphorylated tau protein in the hippocampus and cerebral cortex. The results suggested that STB might protect against cognitive deficits and neurodegeneration induced by Aβ1-42 in mice by regulating the GLT-1 restoration as well as the capacity of GSK3β.

• Authors: Mengjie Xu, Yan Dong, Shutong Wan, Tingxu Yan, Jingdi Cao, Lidan Wu, Kaishun Bi, Ying Jia
• Journal: Physiology & behavior (Physiol Behav) Vol. 167 Pg. 265-273 (12 01 2016) ISSN: 1873-507X [Electronic] United States
• PMID: 27660034 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical References

• Amyloid beta-Peptides
• Cyclooctanes
• Dioxoles
• Excitatory Amino Acid Transporter 2
• Lignans
• Peptide Fragments
• Polycyclic Compounds
• amyloid beta-protein (1-42)
• tau Proteins
• schisantherin B
• Glycogen Synthase Kinase 3 beta

Topics

• Alzheimer Disease (chemically induced, complications)
• Amyloid beta-Peptides (toxicity)
• Analysis of Variance
• Animals
• Brain (drug effects, metabolism)
• Cognition Disorders (chemically induced, drug therapy)
• Cyclooctanes (therapeutic use)
• Dioxoles (therapeutic use)
• Disease Models, Animal
• Enzyme-Linked Immunosorbent Assay
• Excitatory Amino Acid Transporter 2 (metabolism)
• Glycogen Synthase Kinase 3 beta (metabolism)
• Lignans (therapeutic use)
• Locomotion (drug effects)
• Male
• Maze Learning (drug effects)
• Mice
• Peptide Fragments (toxicity)
• Polycyclic Compounds (therapeutic use)
• Time Factors
• tau Proteins (metabolism)