title: The flavonoid baicalein rescues synaptic plasticity and memory deficits in a mouse model of Alzheimer's disease.
abstract: Increasing evidence suggests that disruptions of synaptic functions correlate with the severity of cognitive deficit in Alzheimer's disease (AD). Our previous study demonstrated that baicalein enhances long-term potentiation (LTP) in acute rat hippocampal slices and improves hippocampus-dependent contextual fear conditioning in rats. Given that baicalein possess various biological activities, especially its effects on synaptic plasticity and cognitive function, we examined the effect of baicalein on synaptic function both in vitro and in vivo in AD model. The effect of baicalein on Aβ42 oligomer impaired LTP was investigated by electrophysiological methods. Baicalein was administered orally via drinking water to the APP/PS1 mice and sex- and age-matched wild-type mice. Treatment started at 5 months of age and mice were assessed for cognition and AD-like pathology at 7-month-old. Cognition was analyzed by Morris water maze test, fear conditioning test, and novel object recognition test. Changes in hippocampal 12/15 Lipoxygenase (12/15LO) and glycogen synthase kinase 3β (GSK3β) activity, Aβ production, tau phosphorylation, synaptic plasticity, and dendritic spine density were evaluated. Baicalein prevented Aβ-induced impairments in hippocampal LTP through activation of serine threonine Kinase (Akt) phosphorylation. Long-term oral administration of baicalein inhibited 12/15LO and GSK3β activity, reduced β-secretase enzyme (BACE1), decreased the concentration of total Aβ, and prevented phosphorylation of tau in APP/PS1 mice. Meanwhile, baicalein restored spine number, synaptic plasticity, and memory deficits. Our results strengthen the potential of the flavonoid baicalein as a novel and promising oral bioactive therapeutic agent that prevents memory deficits in AD.
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Neurology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, China; Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi 330029, China.
authors.forename: Xun-Hu
authors.initials: XH
authors.lastname: Gu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi 330029, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi 330029, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wei
authors.affiliation: Department of Medical Experimental Center, Jiangxi Mental Hospital, Nanchang, Jiangxi 330029, China.
authors.forename: Yuan-Jian
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Department of Respiratory Diseases, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China; Nanlou Respiratory Department, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China.
authors.forename: Guo-Gang
authors.initials: GG
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: xiaopingbuxiao@126.com.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Yin
authors.affiliation: Department of Neurology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: wuhansy@126.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000633:toxicity; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D044950:Flavanones / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007858:Learning / Q000187:drug effects / Q000502:physiology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018697:Nootropic Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism / Q000633:toxicity; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C545487:APP protein, human; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D044950:Flavanones; D018697:Nootropic Agents; C508853:PSEN1 protein, human; D010446:Peptide Fragments; D053764:Presenilin-1; C075222:amyloid beta-protein (1-42); C006680:baicalein
keywords: 42 oligomers; A&beta; Alzheimer’s disease; Baicalein; Cognitive function; Hippocampus; Synapse