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Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice

The hippocampal gamma oscillation is important for cognitive function, and its deficit is related to cognitive impairment in Alzheimer’s disease (AD). Recently, it has been recognized that post-translational modification via histone acetylation is a fundamental molecular mechanism for regulating syn...

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Autores principales: Takasu, Keiko, Niidome, Kazuki, Hasegawa, Minoru, Ogawa, Koichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751405/
https://www.ncbi.nlm.nih.gov/pubmed/35027883
http://dx.doi.org/10.3389/fnmol.2021.782206
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author Takasu, Keiko
Niidome, Kazuki
Hasegawa, Minoru
Ogawa, Koichi
author_facet Takasu, Keiko
Niidome, Kazuki
Hasegawa, Minoru
Ogawa, Koichi
author_sort Takasu, Keiko
collection PubMed
description The hippocampal gamma oscillation is important for cognitive function, and its deficit is related to cognitive impairment in Alzheimer’s disease (AD). Recently, it has been recognized that post-translational modification via histone acetylation is a fundamental molecular mechanism for regulating synaptic plasticity and cognitive function. However, little is known regarding the regulation of hippocampal gamma oscillation by histone acetylation. We investigated whether histone acetylation regulated kainate-induced gamma oscillations and their important regulator, fast-spiking interneurons, using acute hippocampal slices of AD model mice (PSAPP transgenic mice). We found a decrease in kainate-induced gamma oscillations in slices from PSAPP mice, accompanied with the increased activity of fast spiking interneurons in basal state and the decreased activity in activated state. The histone deacetylase (HDAC) inhibitor (SAHA, named vorinostat) restored deficits of gamma oscillation in PSAPP mice, accompanied with rescue of activity of fast spiking interneurons in basal and activated state. The effect of SAHA was different from that of the clinical AD drug donepezil, which rescued only function of fast spiking interneurons in basal state. Besides, activator of nuclear receptor family 4a (NR4a) receptor (cytosporone B), as one of the epigenetic modification related to HDAC inhibition, rescued the deficits in gamma oscillations in PSAPP mice. These results suggested a novel mechanism in which HDAC inhibition improved impairment of gamma oscillations in PSAPP mice by restoring the activity of fast spiking interneurons both in basal and activated state. The reversal of gamma oscillation deficits by HDAC inhibition and/or NR4a activation appears to be a potential therapeutic target for treating cognitive impairment in AD patients.
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spelling pubmed-87514052022-01-12 Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice Takasu, Keiko Niidome, Kazuki Hasegawa, Minoru Ogawa, Koichi Front Mol Neurosci Neuroscience The hippocampal gamma oscillation is important for cognitive function, and its deficit is related to cognitive impairment in Alzheimer’s disease (AD). Recently, it has been recognized that post-translational modification via histone acetylation is a fundamental molecular mechanism for regulating synaptic plasticity and cognitive function. However, little is known regarding the regulation of hippocampal gamma oscillation by histone acetylation. We investigated whether histone acetylation regulated kainate-induced gamma oscillations and their important regulator, fast-spiking interneurons, using acute hippocampal slices of AD model mice (PSAPP transgenic mice). We found a decrease in kainate-induced gamma oscillations in slices from PSAPP mice, accompanied with the increased activity of fast spiking interneurons in basal state and the decreased activity in activated state. The histone deacetylase (HDAC) inhibitor (SAHA, named vorinostat) restored deficits of gamma oscillation in PSAPP mice, accompanied with rescue of activity of fast spiking interneurons in basal and activated state. The effect of SAHA was different from that of the clinical AD drug donepezil, which rescued only function of fast spiking interneurons in basal state. Besides, activator of nuclear receptor family 4a (NR4a) receptor (cytosporone B), as one of the epigenetic modification related to HDAC inhibition, rescued the deficits in gamma oscillations in PSAPP mice. These results suggested a novel mechanism in which HDAC inhibition improved impairment of gamma oscillations in PSAPP mice by restoring the activity of fast spiking interneurons both in basal and activated state. The reversal of gamma oscillation deficits by HDAC inhibition and/or NR4a activation appears to be a potential therapeutic target for treating cognitive impairment in AD patients. Frontiers Media S.A. 2021-12-23 /pmc/articles/PMC8751405/ /pubmed/35027883 http://dx.doi.org/10.3389/fnmol.2021.782206 Text en Copyright © 2021 Takasu, Niidome, Hasegawa and Ogawa. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Takasu, Keiko
Niidome, Kazuki
Hasegawa, Minoru
Ogawa, Koichi
Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title_full Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title_fullStr Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title_full_unstemmed Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title_short Histone Deacetylase Inhibitor Improves the Dysfunction of Hippocampal Gamma Oscillations and Fast Spiking Interneurons in Alzheimer’s Disease Model Mice
title_sort histone deacetylase inhibitor improves the dysfunction of hippocampal gamma oscillations and fast spiking interneurons in alzheimer’s disease model mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8751405/
https://www.ncbi.nlm.nih.gov/pubmed/35027883
http://dx.doi.org/10.3389/fnmol.2021.782206
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