Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds
Abstract Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neurona...
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doaj-a89699935efb422bb21f78ff8f7330d32020-11-25T03:40:11ZengBMCActa Neuropathologica Communications2051-59602020-10-018111010.1186/s40478-020-01049-7Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seedsMarta Perez-Rando0Simon Dujardin1Rachel E. Bennett2Caitlin Commins3Tara Nibhanupudy4Bradley T. Hyman5Alzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAlzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAlzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAlzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAlzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAlzheimer Research Unit, Department of Neurology, Massachusetts General HospitalAbstract Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neuronal properties. We utilized high resolution multi-color in situ hybridization technology, RNAScope, in a well-established tau transgenic animal, and found that a subset of neurons in the cortex do not appear to express the transgene, but do develop phospho-tau positive inclusions, consistent with having received tau seeds. Recipient neurons show decreases in their expression of synaptophysin, CAMKIIα, and mouse tau in both young and old animals. These results contrast with neurons that develop tau aggregates and also overexpress the transgene, which have few changes in expression of metabolic and synaptic markers. Taken together, these results strongly suggest that tau propagation impacts neuronal functional integrity.http://link.springer.com/article/10.1186/s40478-020-01049-7Alzheimer’s diseaseNeurofibrillary tanglesTau seedingRNA expression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Marta Perez-Rando Simon Dujardin Rachel E. Bennett Caitlin Commins Tara Nibhanupudy Bradley T. Hyman |
spellingShingle |
Marta Perez-Rando Simon Dujardin Rachel E. Bennett Caitlin Commins Tara Nibhanupudy Bradley T. Hyman Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds Acta Neuropathologica Communications Alzheimer’s disease Neurofibrillary tangles Tau seeding RNA expression |
author_facet |
Marta Perez-Rando Simon Dujardin Rachel E. Bennett Caitlin Commins Tara Nibhanupudy Bradley T. Hyman |
author_sort |
Marta Perez-Rando |
title |
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
title_short |
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
title_full |
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
title_fullStr |
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
title_full_unstemmed |
Synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
title_sort |
synaptic and metabolic gene expression alterations in neurons that are recipients of proteopathic tau seeds |
publisher |
BMC |
series |
Acta Neuropathologica Communications |
issn |
2051-5960 |
publishDate |
2020-10-01 |
description |
Abstract Recent studies suggest that misfolded tau molecules can be released, and taken up by adjacent neurons, propagating proteopathic seeds across neural systems. Yet critical to understanding whether tau propagation is relevant in pathophysiology of disease would be to learn if it alters neuronal properties. We utilized high resolution multi-color in situ hybridization technology, RNAScope, in a well-established tau transgenic animal, and found that a subset of neurons in the cortex do not appear to express the transgene, but do develop phospho-tau positive inclusions, consistent with having received tau seeds. Recipient neurons show decreases in their expression of synaptophysin, CAMKIIα, and mouse tau in both young and old animals. These results contrast with neurons that develop tau aggregates and also overexpress the transgene, which have few changes in expression of metabolic and synaptic markers. Taken together, these results strongly suggest that tau propagation impacts neuronal functional integrity. |
topic |
Alzheimer’s disease Neurofibrillary tangles Tau seeding RNA expression |
url |
http://link.springer.com/article/10.1186/s40478-020-01049-7 |
work_keys_str_mv |
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