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Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice
BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play a...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650290/ https://www.ncbi.nlm.nih.gov/pubmed/34872618 http://dx.doi.org/10.1186/s40035-021-00274-x |
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author | Park, Mincheol Hoang, Gia Minh Nguyen, Thien Lee, Eunkyung Jung, Hyun Jin Choe, Youngshik Lee, Moon Hwan Hwang, Jae Youn Kim, Jae Gwan Kim, Tae |
author_facet | Park, Mincheol Hoang, Gia Minh Nguyen, Thien Lee, Eunkyung Jung, Hyun Jin Choe, Youngshik Lee, Moon Hwan Hwang, Jae Youn Kim, Jae Gwan Kim, Tae |
author_sort | Park, Mincheol |
collection | PubMed |
description | BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently, the therapeutic effect of gamma entrainment in AD mouse models has been reported. Given that ultrasound is an emerging neuromodulation modality, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40 Hz) in an AD mouse model. METHODS: We implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice (n = 12 and 6, respectively). Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. RESULTS: We found that the total Aβ42 levels, especially insoluble Aβ42, in the treatment group decreased in pre- and infra-limbic cortex (PIL) compared to that of the sham treatment group. A reduction in the number of Aβ plaques was also observed in the hippocampus. There was no increase in microbleeding in the transcranial ultrasound stimulation (tUS) group. In addition, the length and number of microglial processes decreased in PIL and hippocampus. Encelphalographic spontaneous gamma power was increased, and cross-frequency coupling was normalized, implying functional improvement after tUS stimulation. CONCLUSION: These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40035-021-00274-x. |
format | Online Article Text |
id | pubmed-8650290 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86502902021-12-07 Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice Park, Mincheol Hoang, Gia Minh Nguyen, Thien Lee, Eunkyung Jung, Hyun Jin Choe, Youngshik Lee, Moon Hwan Hwang, Jae Youn Kim, Jae Gwan Kim, Tae Transl Neurodegener Research BACKGROUND: Alzheimer’s disease (AD) is the most common cause of dementia, and is characterized by amyloid-β (Aβ) plaques and tauopathy. Reducing Aβ has been considered a major AD treatment strategy in pharmacological and non-pharmacological approaches. Impairment of gamma oscillations, which play an important role in perception and cognitive function, has been shown in mouse AD models and human patients. Recently, the therapeutic effect of gamma entrainment in AD mouse models has been reported. Given that ultrasound is an emerging neuromodulation modality, we investigated the effect of ultrasound stimulation pulsed at gamma frequency (40 Hz) in an AD mouse model. METHODS: We implanted electroencephalogram (EEG) electrodes and a piezo-ceramic disc ultrasound transducer on the skull surface of 6-month-old 5×FAD and wild-type control mice (n = 12 and 6, respectively). Six 5×FAD mice were treated with two-hour ultrasound stimulation at 40 Hz daily for two weeks, and the other six mice received sham treatment. Soluble and insoluble Aβ levels in the brain were measured by enzyme-linked immunosorbent assay. Spontaneous EEG gamma power was computed by wavelet analysis, and the brain connectivity was examined with phase-locking value and cross-frequency phase-amplitude coupling. RESULTS: We found that the total Aβ42 levels, especially insoluble Aβ42, in the treatment group decreased in pre- and infra-limbic cortex (PIL) compared to that of the sham treatment group. A reduction in the number of Aβ plaques was also observed in the hippocampus. There was no increase in microbleeding in the transcranial ultrasound stimulation (tUS) group. In addition, the length and number of microglial processes decreased in PIL and hippocampus. Encelphalographic spontaneous gamma power was increased, and cross-frequency coupling was normalized, implying functional improvement after tUS stimulation. CONCLUSION: These results suggest that the transcranial ultrasound-based gamma-band entrainment technique can be an effective therapy for AD by reducing the Aβ load and improving brain connectivity. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40035-021-00274-x. BioMed Central 2021-12-07 /pmc/articles/PMC8650290/ /pubmed/34872618 http://dx.doi.org/10.1186/s40035-021-00274-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Park, Mincheol Hoang, Gia Minh Nguyen, Thien Lee, Eunkyung Jung, Hyun Jin Choe, Youngshik Lee, Moon Hwan Hwang, Jae Youn Kim, Jae Gwan Kim, Tae Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title | Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title_full | Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title_fullStr | Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title_full_unstemmed | Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title_short | Effects of transcranial ultrasound stimulation pulsed at 40 Hz on Aβ plaques and brain rhythms in 5×FAD mice |
title_sort | effects of transcranial ultrasound stimulation pulsed at 40 hz on aβ plaques and brain rhythms in 5×fad mice |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8650290/ https://www.ncbi.nlm.nih.gov/pubmed/34872618 http://dx.doi.org/10.1186/s40035-021-00274-x |
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