Cargando…

Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice

Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epilep...

Descripción completa

Detalles Bibliográficos
Autores principales: Gureviciene, Irina, Ishchenko, Irina, Ziyatdinova, Sofya, Jin, Nanxiang, Lipponen, Arto, Gurevicius, Kestutis, Tanila, Heikki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861424/
https://www.ncbi.nlm.nih.gov/pubmed/31781019
http://dx.doi.org/10.3389/fneur.2019.01151
_version_ 1783471353744064512
author Gureviciene, Irina
Ishchenko, Irina
Ziyatdinova, Sofya
Jin, Nanxiang
Lipponen, Arto
Gurevicius, Kestutis
Tanila, Heikki
author_facet Gureviciene, Irina
Ishchenko, Irina
Ziyatdinova, Sofya
Jin, Nanxiang
Lipponen, Arto
Gurevicius, Kestutis
Tanila, Heikki
author_sort Gureviciene, Irina
collection PubMed
description Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate electrophysiology with underlying pathology at the cellular and molecular level. Using multiple cortical and subcortical electrodes in freely moving APP/PS1 transgenic mice and their wild-type littermates, we identified several types of epileptic spikes among over 15 800 spikes visible with cortical screw electrodes based on their source localization. Cortical spikes associated with muscle twitches, cortico-hippocampal spikes, and spindle and fast-spindle associated spikes were present equally often in both APP/PS1 and wild-type mice, whereas pure cortical spikes were slightly more common in APP/PS1 mice. In contrast, spike-wave discharges, cortico-hippocampal spikes with after hyperpolarization and giant spikes were seen almost exclusively in APP/PS1 mice but only in a subset of them. Interestingly, different subtypes of spikes responded differently to anti-epileptic drugs ethosuximide and levetiracetam. From the translational point most relevant may be the giant spikes generated in the hippocampus that reached an amplitude up to ± 5 mV in the hippocampal channel. As in AD patients, they occurred exclusively during sleep. Further, we could demonstrate that a high number of giant spikes in APP/PS1 mice predicts seizures. These data show that by only adding a pair of hippocampal deep electrodes and EMG to routine cortical epidural screw electrodes and by taking into account underlying cortical oscillations, one can drastically refine the analysis of cortical spike data. This new approach provides a powerful tool to preclinical testing of potential new treatment options for AD related epilepsy.
format Online
Article
Text
id pubmed-6861424
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-68614242019-11-28 Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice Gureviciene, Irina Ishchenko, Irina Ziyatdinova, Sofya Jin, Nanxiang Lipponen, Arto Gurevicius, Kestutis Tanila, Heikki Front Neurol Neurology Epileptic activity without visible convulsions is common in Alzheimer's disease (AD) and may contribute adversely to the disease progress and symptoms. Transgenic mice with amyloid plaque pathology also display epileptic seizures, but those are too infrequent to assess the effect of anti-epileptic treatments. Besides spontaneous seizures, these mice also display frequent epileptic spiking in epidural EEG recordings, and these have provided a means to test potential drug treatment to AD-related epilepsy. However, the origin of EEG spikes in transgenic AD model mice has remained elusive, which makes it difficult to relate electrophysiology with underlying pathology at the cellular and molecular level. Using multiple cortical and subcortical electrodes in freely moving APP/PS1 transgenic mice and their wild-type littermates, we identified several types of epileptic spikes among over 15 800 spikes visible with cortical screw electrodes based on their source localization. Cortical spikes associated with muscle twitches, cortico-hippocampal spikes, and spindle and fast-spindle associated spikes were present equally often in both APP/PS1 and wild-type mice, whereas pure cortical spikes were slightly more common in APP/PS1 mice. In contrast, spike-wave discharges, cortico-hippocampal spikes with after hyperpolarization and giant spikes were seen almost exclusively in APP/PS1 mice but only in a subset of them. Interestingly, different subtypes of spikes responded differently to anti-epileptic drugs ethosuximide and levetiracetam. From the translational point most relevant may be the giant spikes generated in the hippocampus that reached an amplitude up to ± 5 mV in the hippocampal channel. As in AD patients, they occurred exclusively during sleep. Further, we could demonstrate that a high number of giant spikes in APP/PS1 mice predicts seizures. These data show that by only adding a pair of hippocampal deep electrodes and EMG to routine cortical epidural screw electrodes and by taking into account underlying cortical oscillations, one can drastically refine the analysis of cortical spike data. This new approach provides a powerful tool to preclinical testing of potential new treatment options for AD related epilepsy. Frontiers Media S.A. 2019-11-12 /pmc/articles/PMC6861424/ /pubmed/31781019 http://dx.doi.org/10.3389/fneur.2019.01151 Text en Copyright © 2019 Gureviciene, Ishchenko, Ziyatdinova, Jin, Lipponen, Gurevicius and Tanila. http://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 Neurology
Gureviciene, Irina
Ishchenko, Irina
Ziyatdinova, Sofya
Jin, Nanxiang
Lipponen, Arto
Gurevicius, Kestutis
Tanila, Heikki
Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title_full Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title_fullStr Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title_full_unstemmed Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title_short Characterization of Epileptic Spiking Associated With Brain Amyloidosis in APP/PS1 Mice
title_sort characterization of epileptic spiking associated with brain amyloidosis in app/ps1 mice
topic Neurology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861424/
https://www.ncbi.nlm.nih.gov/pubmed/31781019
http://dx.doi.org/10.3389/fneur.2019.01151
work_keys_str_mv AT gurevicieneirina characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT ishchenkoirina characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT ziyatdinovasofya characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT jinnanxiang characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT lipponenarto characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT gureviciuskestutis characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice
AT tanilaheikki characterizationofepilepticspikingassociatedwithbrainamyloidosisinappps1mice