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 -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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-03-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00030/full |
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| author | Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Ian eMahar Ian eMahar Ian eMahar Maria Antonietta eDavoli Maria Antonietta eDavoli Jean-Guy eChabot Jean-Guy eChabot Naguib eMechawar Naguib eMechawar Naguib eMechawar Naguib eMechawar Rémi eQuirion Rémi eQuirion Slavica eKrantic Slavica eKrantic Slavica eKrantic Slavica eKrantic |
| author_facet | Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Ian eMahar Ian eMahar Ian eMahar Maria Antonietta eDavoli Maria Antonietta eDavoli Jean-Guy eChabot Jean-Guy eChabot Naguib eMechawar Naguib eMechawar Naguib eMechawar Naguib eMechawar Rémi eQuirion Rémi eQuirion Slavica eKrantic Slavica eKrantic Slavica eKrantic Slavica eKrantic |
| author_sort | Marilia Silva Albequerque |
| collection | DOAJ |
| description | Hippocampal network activity is predominantly coordinated by -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. |
| first_indexed | 2024-12-17T10:44:43Z |
| format | Article |
| id | doaj.art-e738c8b79b424b4d9a8384183f145101 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-17T10:44:43Z |
| publishDate | 2015-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-e738c8b79b424b4d9a8384183f1451012022-12-21T21:52:09ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652015-03-01710.3389/fnagi.2015.00030135441Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer’s diseaseMarilia Silva Albequerque0Marilia Silva Albequerque1Marilia Silva Albequerque2Marilia Silva Albequerque3Ian eMahar4Ian eMahar5Ian eMahar6Maria Antonietta eDavoli7Maria Antonietta eDavoli8Jean-Guy eChabot9Jean-Guy eChabot10Naguib eMechawar11Naguib eMechawar12Naguib eMechawar13Naguib eMechawar14Rémi eQuirion15Rémi eQuirion16Slavica eKrantic17Slavica eKrantic18Slavica eKrantic19Slavica eKrantic20Douglas Mental Health University InstituteUniversidade de São PauloUniversidade de São PauloResearch Group on Neuropharmacology of AgingDouglas Mental Health University InstituteDouglas Mental Health University InstituteMcGill UniversityDouglas Mental Health University InstituteDouglas Mental Health University InstituteDouglas Mental Health University InstituteMcGill UniversityDouglas Mental Health University InstituteDouglas Mental Health University InstituteMcGill UniversityMcGill UniversityDouglas Mental Health University InstituteMcGill UniversityDouglas Mental Health University InstituteMcGill UniversityMcGill UniversitySorbonne Universités, UPMC Univ Paris 06, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des CordeliersHippocampal network activity is predominantly coordinated by -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.http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00030/fullNeuropeptide YSomatostatinAlzheimer’s diseaseparvalbuminhippocampal sub-regions |
| spellingShingle | Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Marilia Silva Albequerque Ian eMahar Ian eMahar Ian eMahar Maria Antonietta eDavoli Maria Antonietta eDavoli Jean-Guy eChabot Jean-Guy eChabot Naguib eMechawar Naguib eMechawar Naguib eMechawar Naguib eMechawar Rémi eQuirion Rémi eQuirion Slavica eKrantic Slavica eKrantic Slavica eKrantic Slavica eKrantic Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer’s disease Frontiers in Aging Neuroscience Neuropeptide Y Somatostatin Alzheimer’s disease parvalbumin hippocampal sub-regions |
| 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 | Neuropeptide Y Somatostatin Alzheimer’s disease parvalbumin hippocampal sub-regions |
| url | http://journal.frontiersin.org/Journal/10.3389/fnagi.2015.00030/full |
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