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dc.creatorKshirsagar, Sudhir (TTUHSC)
dc.creatorAlvir, Rainier Vladlen (TTUHSC)
dc.creatorHindle, Ashly (TTUHSC)
dc.creatorKumar, Subodh (TTUHSC)
dc.creatorVijayan, Murali (TTUHSC)
dc.creatorPradeepkiran, Jangampalli Adi (TTUHSC)
dc.creatorReddy, Arubala (TTU)
dc.creatorRamasubramanian, Bhagavathi (TTUHSC)
dc.creatorReddy, P. Hemachandra (TTUHSC)
dc.date.accessioned2022-05-09T15:13:32Z
dc.date.available2022-05-09T15:13:32Z
dc.date.issued2022
dc.identifier.citationKshirsagar S, Alvir RV, Hindle A, Kumar S, Vijayan M, Pradeepkiran JA, Reddy AP, Ramasubramanian B, Reddy PH. Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Disease. Cells. 2022; 11(4):733. https://doi.org/10.3390/cells11040733en_US
dc.identifier.urihttps://doi.org/10.3390/cells11040733
dc.identifier.urihttps://hdl.handle.net/2346/89156
dc.description© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).en_US
dc.description.abstractThe purpose of our study is to investigate early cellular, molecular, morphological and behavioral changes in humanized amyloid-beta-knock-in (hAbKI) mice. Using seven-month-old homozygous hAbKI mice, we studied behavioral phenotype parameters, including spatial learning and memory (Morris Water Maze), locomotor activity (open field), working memory (Y-maze) and motor coordination (rotarod); mRNA abundance, protein levels, soluble amyloid-beta 40 and 42 levels and regional immunoreactivities of key markers of mitochondrial dynamics, mitochondrial biogenesis, synaptic health, mitophagy and autophagy; mitochondrial function and using transmission electron microscopy & Golgi–Cox staining, we assessed mitochondrial morphology and dendritic spines. Our extensive behavioral analysis revealed that seven-month-old hAbKI mice showed impairments in motor coordination, reduced locomotor and exploration activities, impairments in working memory and spatial learning and memory. Our mRNA and protein analyses revealed the increased expression of mitochondrial-fission genes and reduced expression of mitochondrial-fusion, mitochondrial-biogenesis, synaptic, autophagy and mitophagy genes in seven-month-old hAbKI mice. An immunofluorescence analysis revealed altered immunoreactivities and agreed with the immunoblot results. Transmission-electron-microscopy data revealed increased mitochondrial fragmentation and reduced mitochondrial length in both hippocampal and cortical tissues of seven-month-old hAbKI mice and mitochondrial function defective. A Golgi–Cox-staining analysis revealed reduced dendritic spines in both cerebral cortices and hippocampi of hAbKI mice. Soluble amyloid-beta (1–40 and 1–42) were detected in three-month-old hAbKI mice and progressively increased in seven-month-old mice. These observations suggest that the human amyloid-beta peptide is sufficient to cause behavioral, mitochondrial, synaptic and ultrastructural changes in seven-month-old hAbKI mice. Our study findings also suggest that hAbKI mice might serve as a model for preclinical studies of preventive therapies.en_US
dc.language.isoengen_US
dc.subjectAmyloid Betaen_US
dc.subjectMitochondriaen_US
dc.subjectLate-Onset Alzheimer's Diseaseen_US
dc.subjectDendritic Spinesen_US
dc.titleEarly Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Diseaseen_US
dc.typeArticleen_US


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