MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease

Morton, Hallie; Sawant, Neha; Orlov, Erika; Bunquin, Lloyd E; Pradeepkiran, Jangampalli Adi; Alvir, Razelle; Reddy, P. Hemachandra

doi:10.1016/j.redox.2021.102182

Cited by 30 publications

(21 citation statements)

References 45 publications

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“…Using the Morris-water-maze (MWM) test, we assessed spatial long-term memory and learning in hAbKI and WT mice [ 31 , 32 ]. The MWM test was conducted in a 120 cm-diameter, 50 cm-deep tank filled with opacified water (Utrecht Art Supplies, Cranbury, NJ, USA) kept at 25 ± 0.5 °C.…”

Section: Methodsmentioning

confidence: 99%

“…If the animal did not find the platform within one minute, they were placed on the platform using the net for 3 s. After every trial, the animal was dried with a towel and placed into a holding cage. Animals were video tracked using ANY-Maze ® software (Stoelting, Wood Dale, IL, USA), and behavioral parameters, including average time to find the platform, distance traveled, and average speed were assessed [ 30 , 32 ].…”

Section: Methodsmentioning

confidence: 99%

“…To determine the immunoreactivity and intensity of mitochondrial dynamics, biogenesis, synaptic, and autophagy/mitophagy proteins, we performed immunofluorescence analysis using brain sections of 7-month-old hAbKI and WT mice as described in our lab publications [ 30 , 32 , 33 ]. Details of antibody dilutions are given in Table 3 .…”

Section: Methodsmentioning

confidence: 99%

“…Dendritic spines of neurons in the brains of 7-month-old WT, hAbKI mice were detected by Golgi–Cox staining, which was performed using the FD Rapid GolgiStain Kit (PK401, FD NeuroTechnologies, Columbia, MD, USA) as described earlier [ 30 , 32 , 33 ]. All procedures were performed under dark conditions.…”

Section: Methodsmentioning

confidence: 99%

“…To determine the mitochondrial number and size, we performed transmission electron microscopy in hippocampal and cortical sections of 7-month-old WT, hAbKI mice using methods described in lab publications [ 30 , 32 , 33 ]. Analyses of mitochondria number and size in WT and hAbKI mouse brains were performed using Image J software.…”

Section: Methodsmentioning

confidence: 99%

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Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Disease

Kshirsagar

Alvir

Hindle

et al. 2022

Cells

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The 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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Disease

Kshirsagar

Alvir

Hindle

et al. 2022

Cells

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Methods to Study Mitochondria: Techniques Used to Study the Effects of Age‐Related Diseases Including Alzheimer's

2023

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Various laboratories across the world have developed methods to study mitochondrial proteins/markers through extraction of mitochondrial RNA and protein to assess mitophagy/autophagy in Alzheimer's disease and other age‐related diseases. Techniques outlined in this article include qRT‐PCR, immunoblotting, immunofluorescence, transmission electron microscopy, Seahorse bioanalysis, staining for mitochondrial membrane potential, detection of mitophagy, and mitochondrial functional assays. Most of these techniques have been performed in vitro (in human and mouse neuronal cell lines transfected with mutant amyloid precursor protein or tau protein cDNAs) and in vivo (in brain tissues from different mouse models of Alzheimer's and other neurological diseases). Mitochondrial abnormalities in Alzheimer's disease have taken various forms, including excessive reactive oxygen species production, mitochondrial calcium dyshomeostasis, loss of ATP, defects in mitochondrial dynamics and transport, and mitophagy. Mitochondrial dysfunction is largely involved in aging; age‐related diseases such as cancer, diabetes, and obesity; and neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, multiple sclerosis, and others. The goal of this article is to make protocols/methods available to students, scholars, and researchers of mitochondria in order to facilitate future mitochondrial studies. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Analyzing mitochondrial gene expression in mouse brain tissue and HT22 cells by qRT‐PCR Basic Protocol 2: Analyzing protein expression in mouse brain tissue and HT22 cells by immunoblotting Basic Protocol 3: Immunofluorescence staining of cells and tissue sections Basic Protocol 4: Staining for mitochondrial membrane potential Basic Protocol 5: Assessing mitochondrial structure by transmission electron microscopy Basic Protocol 6: Methods for detecting mitophagy Basic Protocol 7: Bioenergetics assay via Seahorse Basic Protocol 8: Assays for mitochondrial function

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Targeting Novel microRNAs in Developing Novel Alzheimer's Disease Treatments

2022

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MicroRNA-455-3p improves synaptic, cognitive functions and extends lifespan: Relevance to Alzheimer's disease

Cited by 30 publications

References 45 publications

Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Disease

Early Cellular, Molecular, Morphological and Behavioral Changes in the Humanized Amyloid-Beta-Knock-In Mouse Model of Late-Onset Alzheimer’s Disease

Methods to Study Mitochondria: Techniques Used to Study the Effects of Age‐Related Diseases Including Alzheimer's

Targeting Novel microRNAs in Developing Novel Alzheimer's Disease Treatments

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