Young Blood Rescues the Cognition of Alzheimer's Model Mice by Restoring the Hippocampal Cholinergic Circuit. (1st October 2019)

• Record Type: Journal Article
• Authors: Xia, Endi; Xu, Fengyan; Hu, Changbin; Kumal, Jay Prakash Prasad; Tang, Xudong; Mao, Dongsheng; Li, Yixuan; Wu, Di; Zhang, Rui; Wu, Shuliang; Sun, Liang
• Is Part Of: Neuroscience. Volume 417(2019)
• Page Start: 57
• Page End: 69
• Publication Date: 2019-10-01
• Subjects: A.U. arbitrary unit -- A-APP/PS1 + AS aged APP/PS1 mice plus aged serum -- A-APP/PS1 + YS aged APP/PS1 mice plus young serum -- A-APP/PS1 + YS + Benz aged APP/PS1 mice plus young serum plus benztropine -- AD Alzheimer's disease -- ANOVA analysis of variance -- Aβ amyloid-β -- BDL below detectable limit -- BDNF brain-derived neurotrophic factor -- BF basal forebrain -- BMP9 bone morphogenic protein 9 -- ChAT choline acetyltransferase -- CNS central nervous system -- CREB cyclic AMP response element-binding protein -- DAB dimethylaminobenzaldehyde -- DB diagonal band nuclei -- FOXO1 Forkhead box protein O1 -- GDF11 growth differentiation factor 11 -- Hp hippocampus -- HRP conjugated to horseradish peroxidase -- LTP long-term potentiation -- mAChR muscarinic acetylcholine receptor -- MS medial septal nucleus -- nAChRs nicotinic acetylcholine receptors -- NB nucleus basalis -- NGF nerve growth factor -- REST repressor element 1-silencing transcription factor -- SEM standard error of the mean -- SI substantia innominata -- TEM Transmission electron microscopy -- TIMP2 tissue inhibitor of metalloproteinases 2 -- Y-APP/PS1 + YS young the APP/PS1 mice plus young serum -- μg/mgprot μg per microgram tissue protein; Alzheimer's disease -- Young blood serum -- Memory -- Cholinergic transmission; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.08.010
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: An increasing number of studies have demonstrated the benefits of young individual-derived blood for aging-related diseases. However, the effects of young blood on the cognitive and cholinergic transmission defects in aging-associated Alzheimer's disease (AD) remain elusive. In the current study, we showed that young blood serum delivered intravenously attenuated deficits in hippocampal-dependent learning and memory, alleviated hippocampal Aβ plaque pathology, restored synapse formation and synaptic plasticity, repaired the hippocampal cholinergic circuit, and triggered several canonical neuroprotective mechanisms [including repressor element 1-silencing transcription factor (REST)/Forkhead box protein O1 (FOXO1) signaling] in aged AD model mice. However, pharmacological blockage of hippocampal cholinergic activity nearly abrogated the neuroprotective actions of young blood serum in AD mice. Thus, our findings suggest that exogenous young blood serum exerts therapeutic effects on AD-associated cognitive disorders and pathology by promoting hippocampal cholinergic input and simultaneously activating other neuroprotective mechanisms. Highlights: Young blood serum treatment ameliorated hippocampal-dependent cognitive disorder in AD model mice. Young blood serum treatment repressed Aβ pathology, restored synaptogenesis and synaptic plasticity in AD model mice. The therapeutic effects of young blood serum in AD were mediated partially by renewing hippocampal cholinergic input. The therapeutic effects were associated with canonical neuroprotective mechanisms including REST/FOXO1 signaling.