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Front Aging Neurosci. 2015 Mar 24;7:30. doi: 10.3389/fnagi.2015.00030. eCollection 2015.

Regional and sub-regional differences in hippocampal GABAergic neuronal vulnerability in the TgCRND8 mouse model of Alzheimer's disease.

Author information

1
Douglas Mental Health University Institute Verdun, QC, Canada ; Laboratory of Biomedicine and Biotechnology, School of Arts, Sciences and Humanities, Universidade de São Paulo São Paulo, Brazil ; Graduation Course on Pharmacology, Institute of Biomedical Sciences, Universidade de São Paulo São Paulo, Brazil ; Research Group on Neuropharmacology of Aging São Paulo, Brazil.
2
Douglas Mental Health University Institute Verdun, QC, Canada ; McGill Group for Suicide Studies, Douglas Mental Health University Institute Verdun, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada.
3
Douglas Mental Health University Institute Verdun, QC, Canada ; McGill Group for Suicide Studies, Douglas Mental Health University Institute Verdun, QC, Canada.
4
Douglas Mental Health University Institute Verdun, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada.
5
Douglas Mental Health University Institute Verdun, QC, Canada ; McGill Group for Suicide Studies, Douglas Mental Health University Institute Verdun, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada ; Department of Psychiatry, McGill University Montreal, QC, Canada.
6
Douglas Mental Health University Institute Verdun, QC, Canada ; Integrated Program in Neuroscience, McGill University Montreal, QC, Canada ; Department of Psychiatry, McGill University Montreal, QC, Canada ; Centre de Recherche des Cordeliers, INSERM, Université Paris Descartes, Sorbonne Paris Cité, UMR_S 1138, Université Pierre et Marie Curie Univ Paris 06, Sorbonne Universités Paris, France.

Abstract

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.

KEYWORDS:

Alzheimer's disease; hippocampal sub-regions; neuropeptide Y; parvalbumin; somatostatin

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