title: Risperidone ameliorated Aβ1-42-induced cognitive and hippocampal synaptic impairments in mice.
abstract: Alzheimer's disease (AD) is a complex neurodegenerative disorder with cognitive impairment and major neuropathologic hallmark of amyloid-beta (Aβ) 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 Aβ1-42-induced cognitive dysfunction in both long-term and short-term memory. Furthermore, ELISA assay was conducted to measure the levels of Aβ1-42,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, GSK3β and Caspase-3 protein were measured. For behavior tests, the results showed that Risperidone significantly reversed the Aβ1-42-induced dysfunction in learning, memory, locomotor activity and exploratory behavior. As detected by ELISA assay, risperidone decreased the levels of Aβ1-42, BACE1 and p-Tau in the hippocampus and cortex of AD model mice. Biochemical assay showed that Risperidone reversed the Aβ1-42-induced decrease of cell viability and mitochondrial membrane potential in cultured cortical neurons. The expression of p-Akt was increased, whereas the expression of GSK3β 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 Aβ generation and improving cognitive impairment in mice.
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Baojuan
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China.
authors.forename: Muhammad Zahid
authors.initials: MZ
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, China Pharmaceutical University, Nanjing 210009, China. Electronic address: heling92@hotmail.com.
authors.forename: Ling
authors.initials: L
authors.lastname: He
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D002478:Cells, Cultured; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D010766:Phosphorylation / Q000187:drug effects; D011897:Random Allocation; D018967:Risperidone / Q000494:pharmacology*; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C558298:Mapt protein, mouse; D018696:Neuroprotective Agents; D018697:Nootropic Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse; D018967:Risperidone
keywords: Alzheimer’s disease; Aβ(1-42); Cognitive impairment; Risperidone