Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage

Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. The presence of large numbers of senile plaques, neurofibrillary tangles, and cerebral atrophy is the characteristic feature of AD. Amyloid β peptide (Aβ), derived from th...

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Main Authors: Yuji Kamikubo, Hao Jin, Yiyao Zhou, Kazue Niisato, Yoshie Hashimoto, Nobumasa Takasugi, Takashi Sakurai
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-01-01
Series:Frontiers in Molecular Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnmol.2022.1068990/full
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author Yuji Kamikubo
Hao Jin
Yiyao Zhou
Kazue Niisato
Yoshie Hashimoto
Nobumasa Takasugi
Takashi Sakurai
author_facet Yuji Kamikubo
Hao Jin
Yiyao Zhou
Kazue Niisato
Yoshie Hashimoto
Nobumasa Takasugi
Takashi Sakurai
author_sort Yuji Kamikubo
collection DOAJ
description Alzheimer’s disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. The presence of large numbers of senile plaques, neurofibrillary tangles, and cerebral atrophy is the characteristic feature of AD. Amyloid β peptide (Aβ), derived from the amyloid precursor protein (APP), is the main component of senile plaques. AD has been extensively studied using methods involving cell lines, primary cultures of neural cells, and animal models; however, discrepancies have been observed between these methods. Dissociated cultures lose the brain’s tissue architecture, including neural circuits, glial cells, and extracellular matrix. Experiments with animal models are lengthy and require laborious monitoring of multiple parameters. Therefore, it is necessary to combine these experimental models to understand the pathology of AD. An experimental platform amenable to continuous observation and experimental manipulation is required to analyze long-term neuronal development, plasticity, and progressive neurodegenerative diseases. In the current study, we provide a practical method to slice and cultivate rodent hippocampus to investigate the cleavage of APP and secretion of Aβ in an ex vivo model. Furthermore, we provide basic information on Aβ secretion using slice cultures. Using our optimized method, dozens to hundreds of long-term stable slice cultures can be coordinated simultaneously. Our findings are valuable for analyses of AD mouse models and senile plaque formation culture models.
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spelling doaj.art-2c6c03ba0eb2414998ed1d54d86a07d12023-01-06T13:29:25ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992023-01-011510.3389/fnmol.2022.10689901068990Ex vivo analysis platforms for monitoring amyloid precursor protein cleavageYuji KamikuboHao JinYiyao ZhouKazue NiisatoYoshie HashimotoNobumasa TakasugiTakashi SakuraiAlzheimer’s disease (AD) is a progressive neurodegenerative brain disorder and the most common cause of dementia in the elderly. The presence of large numbers of senile plaques, neurofibrillary tangles, and cerebral atrophy is the characteristic feature of AD. Amyloid β peptide (Aβ), derived from the amyloid precursor protein (APP), is the main component of senile plaques. AD has been extensively studied using methods involving cell lines, primary cultures of neural cells, and animal models; however, discrepancies have been observed between these methods. Dissociated cultures lose the brain’s tissue architecture, including neural circuits, glial cells, and extracellular matrix. Experiments with animal models are lengthy and require laborious monitoring of multiple parameters. Therefore, it is necessary to combine these experimental models to understand the pathology of AD. An experimental platform amenable to continuous observation and experimental manipulation is required to analyze long-term neuronal development, plasticity, and progressive neurodegenerative diseases. In the current study, we provide a practical method to slice and cultivate rodent hippocampus to investigate the cleavage of APP and secretion of Aβ in an ex vivo model. Furthermore, we provide basic information on Aβ secretion using slice cultures. Using our optimized method, dozens to hundreds of long-term stable slice cultures can be coordinated simultaneously. Our findings are valuable for analyses of AD mouse models and senile plaque formation culture models.https://www.frontiersin.org/articles/10.3389/fnmol.2022.1068990/fullAlzheimer’s diseaseamyloid βneurodegenerative diseaseorganotypic brain culturehippocampussecretase
spellingShingle Yuji Kamikubo
Hao Jin
Yiyao Zhou
Kazue Niisato
Yoshie Hashimoto
Nobumasa Takasugi
Takashi Sakurai
Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
Frontiers in Molecular Neuroscience
Alzheimer’s disease
amyloid β
neurodegenerative disease
organotypic brain culture
hippocampus
secretase
title Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
title_full Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
title_fullStr Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
title_full_unstemmed Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
title_short Ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
title_sort ex vivo analysis platforms for monitoring amyloid precursor protein cleavage
topic Alzheimer’s disease
amyloid β
neurodegenerative disease
organotypic brain culture
hippocampus
secretase
url https://www.frontiersin.org/articles/10.3389/fnmol.2022.1068990/full
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