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

Accumulation of amyloid beta (A(3) 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 kinase3 beta (GSK3 beta) may be the pathological links between A beta 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 A beta(1-42), and its possible mechanism were Glutamate transporter GLT-1, tau and GSK3 beta. It was found that successive intracerebroventricular (ICV) administration of STB (0.15 mg/kg) for 5 days significantly attenuated A beta(1-42)-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 0.15 mg/kg restored the activities of GLT-1 and GSK3 beta 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 A beta(1-42) in mice by regulating the GLT-1 restoration as well as the capacity of GSK3 beta. (C) 2016 Elsevier Inc. All rights reserved.