Risperidone ameliorated Aβ1-42-induced cognitive and hippocampal synaptic impairments in mice

Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (A(3) peptides. Risperidone, an atypical antipsychotic, can improve concentration and cognitive deficit in schizophrenia patients. In this study, behavior tests including Morris Water Maze test, Step-through passive avoidance test, Open Field test, Step-Down test, Hole-Board test and Novel object recognition test were preformed to examine the effect of Risperidone on A beta(1-42)-induced cognitive dysfunction in both long-term and short-term memory. Furthermore, ELISA assay was conducted to measure the levels of A beta(1-42) BACE1 and p-Tau in the hippocampus and cortex. Moreover, primary cortical neuron was cultured in vitro, and the cell viability, mitochondrial membrane potential, and the level of p-Akt, GSK3 beta and Caspase-3 protein were measured. For behavior tests, the results showed that Risperidone significantly reversed the A beta(1-42)-induced dysfunction in learning, memory, locomotor activity and exploratory behavior. As detected by ELISA assay, risperidone decreased the levels of A beta(1-42), BACE1 and p-Tau in the hippocampus and cortex of AD model mice. Biochemical assay showed that Risperidone reversed the A beta(1-42)-induced decrease of cell viability and mitochondria' membrane potential in cultured cortical neurons. The expression of p-Akt was increased, whereas the expression of GSK3 beta and Caspase-3 were decreased. These results suggested that Risperidone may be used as a promising candidate for AD treatment, for its effects of inhibiting A beta generation and improving cognitive impairment in mice. (C)2017 Elsevier B.V. All rights reserved.