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Open AccessArticle

Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease

1
Synaptic Structure Laboratory, Instituto de Investigación en Discapacidades Neurológicas (IDINE), Dept. Ciencias Médicas, Facultad de Medicina, Universidad Castilla-La Mancha, Campus Biosanitario, C/Almansa 14, 02008 Albacete, Spain
2
Departamento de Sistemas Informáticos, Escuela Superior de Ingeniería Informática, Universidad de Castilla-La Mancha, 02071 Albacete, Spain
3
Grenoble Institut des Neurosciences, Université Grenoble Alpes, BP 170 Grenoble, France
4
Institute of Science and Technology (IST Austria), Am Campus 1, A-3400 Klosterneuburg, Austria
5
Division of Brain Structure and Function, Faculty of Medical Science, University of Fukui, Fukui 910-1193, Japan
6
Life Science Innovation Center, University of Fukui, Fukui 910-1193, Japan
7
Research Center for Child Mental Development, Faculty of Medical Science, University of Fukui, Fukui 910-1193, Japan
*
Author to whom correspondence should be addressed.
Present address: University of the Basque Country (UPV/EHU), 48940 Leioa, Spain. Ikerbasque, Basque Foundation for Science, 48013 Bilbao, Spain.
Int. J. Mol. Sci. 2020, 21(7), 2459; https://doi.org/10.3390/ijms21072459
Received: 30 January 2020 / Revised: 27 March 2020 / Accepted: 31 March 2020 / Published: 2 April 2020
(This article belongs to the Special Issue Glutamate Receptors in Health and Disease II)
Metabotropic γ-aminobutyric acid (GABAB) receptors contribute to the control of network activity and information processing in hippocampal circuits by regulating neuronal excitability and synaptic transmission. The dysfunction in the dentate gyrus (DG) has been implicated in Alzheimer´s disease (AD). Given the involvement of GABAB receptors in AD, to determine their subcellular localisation and possible alteration in granule cells of the DG in a mouse model of AD at 12 months of age, we used high-resolution immunoelectron microscopic analysis. Immunohistochemistry at the light microscopic level showed that the regional and cellular expression pattern of GABAB1 was similar in an AD model mouse expressing mutated human amyloid precursor protein and presenilin1 (APP/PS1) and in age-matched wild type mice. High-resolution immunoelectron microscopy revealed a distance-dependent gradient of immunolabelling for GABAB receptors, increasing from proximal to distal dendrites in both wild type and APP/PS1 mice. However, the overall density of GABAB receptors at the neuronal surface of these postsynaptic compartments of granule cells was significantly reduced in APP/PS1 mice. Parallel to this reduction in surface receptors, we found a significant increase in GABAB1 at cytoplasmic sites. GABAB receptors were also detected at presynaptic sites in the molecular layer of the DG. We also found a decrease in plasma membrane GABAB receptors in axon terminals contacting dendritic spines of granule cells, which was more pronounced in the outer than in the inner molecular layer. Altogether, our data showing post- and presynaptic reduction in surface GABAB receptors in the DG suggest the alteration of the GABAB-mediated modulation of excitability and synaptic transmission in granule cells, which may contribute to the cognitive dysfunctions in the APP/PS1 model of AD. View Full-Text
Keywords: Alzheimer´s disease; hippocampus; GABAB receptors; ion channels; immunohistochemistry; electron microscopy; freeze-fracture; mouse model; dentate gyrus Alzheimer´s disease; hippocampus; GABAB receptors; ion channels; immunohistochemistry; electron microscopy; freeze-fracture; mouse model; dentate gyrus
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MDPI and ACS Style

Martín-Belmonte, A.; Aguado, C.; Alfaro-Ruíz, R.; Moreno-Martínez, A.E.; de la Ossa, L.; Martínez-Hernández, J.; Buisson, A.; Shigemoto, R.; Fukazawa, Y.; Luján, R. Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 2459. https://doi.org/10.3390/ijms21072459

AMA Style

Martín-Belmonte A, Aguado C, Alfaro-Ruíz R, Moreno-Martínez AE, de la Ossa L, Martínez-Hernández J, Buisson A, Shigemoto R, Fukazawa Y, Luján R. Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease. International Journal of Molecular Sciences. 2020; 21(7):2459. https://doi.org/10.3390/ijms21072459

Chicago/Turabian Style

Martín-Belmonte, Alejandro; Aguado, Carolina; Alfaro-Ruíz, Rocío; Moreno-Martínez, Ana E.; de la Ossa, Luis; Martínez-Hernández, José; Buisson, Alain; Shigemoto, Ryuichi; Fukazawa, Yugo; Luján, Rafael. 2020. "Density of GABAB Receptors Is Reduced in Granule Cells of the Hippocampus in a Mouse Model of Alzheimer’s Disease" Int. J. Mol. Sci. 21, no. 7: 2459. https://doi.org/10.3390/ijms21072459

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