Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease
Hippocampal network activity is predominantly coordinated by γ-amino-butyric acid (GABA)ergic neurons. We have previously hypothesized that the altered excitability of hippocampal neurons in Alzheimer's disease (AD), which manifests as increased in vivo susceptibility to seizures in the TgCRND8...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2015
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371759/ https://www.ncbi.nlm.nih.gov/pubmed/25852545 http://dx.doi.org/10.3389/fnagi.2015.00030 |
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author | Albuquerque, Marilia S. Mahar, Ian Davoli, Maria Antonietta Chabot, Jean-Guy Mechawar, Naguib Quirion, Rémi Krantic, Slavica |
author_facet | Albuquerque, Marilia S. Mahar, Ian Davoli, Maria Antonietta Chabot, Jean-Guy Mechawar, Naguib Quirion, Rémi Krantic, Slavica |
author_sort | Albuquerque, Marilia S. |
collection | PubMed |
description | Hippocampal network activity is predominantly coordinated by γ-amino-butyric acid (GABA)ergic neurons. We have previously hypothesized that the altered excitability of hippocampal neurons in Alzheimer's disease (AD), which manifests as increased in vivo susceptibility to seizures in the TgCRND8 mouse model of AD, may be related to disruption of hippocampal GABAergic neurons. In agreement, our previous study in TgCRND8 mice has shown that hippocampal GABAergic neurons are more vulnerable to AD-related neuropathology than other types of neurons. To further explore the mechanisms behind the observed decrease of GABAergic neurons in 6 month-old TgCRND8 mice, we assessed the relative proportion of somatostatin (SOM), neuropeptide Y (NPY) and paravalbumin (PV) sub-types of GABAergic neurons at the regional and sub-regional level of the hippocampus. We found that NPY expressing GABAergic neurons were the most affected, as they were decreased in CA1-CA2 (pyramidal-, stratum oriens, stratum radiatum and molecular layers), CA3 (specifically in the stratum oriens) and dentate gyrus (specifically in the polymorphic layer) in TgCRND8 mice as compared to non-transgenic controls. SOM expressing GABAergic neurons were decreased in CA1-CA2 (specifically in the stratum oriens) and in the stratum radiatum of CA3, whereas PV neurons were significantly altered in stratum oriens sub-region of CA3. Taken together, these data provide new evidence for the relevance of hippocampal GABAergic neuronal network disruption as a mechanism underlying AD sequelae such as aberrant neuronal excitability, and further point to complex hippocampal regional and sub-regional variation in susceptibility to AD-related neuronal loss. |
format | Online Article Text |
id | pubmed-4371759 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-43717592015-04-07 Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease Albuquerque, Marilia S. Mahar, Ian Davoli, Maria Antonietta Chabot, Jean-Guy Mechawar, Naguib Quirion, Rémi Krantic, Slavica Front Aging Neurosci Neuroscience Hippocampal network activity is predominantly coordinated by γ-amino-butyric acid (GABA)ergic neurons. We have previously hypothesized that the altered excitability of hippocampal neurons in Alzheimer's disease (AD), which manifests as increased in vivo susceptibility to seizures in the TgCRND8 mouse model of AD, may be related to disruption of hippocampal GABAergic neurons. In agreement, our previous study in TgCRND8 mice has shown that hippocampal GABAergic neurons are more vulnerable to AD-related neuropathology than other types of neurons. To further explore the mechanisms behind the observed decrease of GABAergic neurons in 6 month-old TgCRND8 mice, we assessed the relative proportion of somatostatin (SOM), neuropeptide Y (NPY) and paravalbumin (PV) sub-types of GABAergic neurons at the regional and sub-regional level of the hippocampus. We found that NPY expressing GABAergic neurons were the most affected, as they were decreased in CA1-CA2 (pyramidal-, stratum oriens, stratum radiatum and molecular layers), CA3 (specifically in the stratum oriens) and dentate gyrus (specifically in the polymorphic layer) in TgCRND8 mice as compared to non-transgenic controls. SOM expressing GABAergic neurons were decreased in CA1-CA2 (specifically in the stratum oriens) and in the stratum radiatum of CA3, whereas PV neurons were significantly altered in stratum oriens sub-region of CA3. Taken together, these data provide new evidence for the relevance of hippocampal GABAergic neuronal network disruption as a mechanism underlying AD sequelae such as aberrant neuronal excitability, and further point to complex hippocampal regional and sub-regional variation in susceptibility to AD-related neuronal loss. Frontiers Media S.A. 2015-03-24 /pmc/articles/PMC4371759/ /pubmed/25852545 http://dx.doi.org/10.3389/fnagi.2015.00030 Text en Copyright © 2015 Albuquerque, Mahar, Davoli, Chabot, Mechawar, Quirion and Krantic. 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) or licensor 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 Albuquerque, Marilia S. Mahar, Ian Davoli, Maria Antonietta Chabot, Jean-Guy Mechawar, Naguib Quirion, Rémi Krantic, Slavica Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title | Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title_full | Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title_fullStr | Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title_full_unstemmed | Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title_short | Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease |
title_sort | regional and sub-regional differences in hippocampal gabaergic neuronal vulnerability in the tgcrnd8 mouse model of alzheimer's disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4371759/ https://www.ncbi.nlm.nih.gov/pubmed/25852545 http://dx.doi.org/10.3389/fnagi.2015.00030 |
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