Affiliations: [a] Department of Psychiatry and Psychotherapy, Charité – University Medicine Berlin, Campus Benjamin Franklin, Berlin, Germany | [b] Cellular Neurosciences, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany | [c] INSERM U840, College de France, Paris, France | [d] Institute of Biomedical and Health Engineering, Shenzhen Institute of Advanced Technology, Chinese Academy of Science, Shenzhen, China | [e] Lilly Research Laboratories, Neuroscience Division; Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana, USA
Correspondence:
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Corresponding author: Dr. Oliver Peters, Department of Psychiatry and Psychotherapy, Charité – University Medicine Berlin, Campus Benjamin Franklin, Eschenallee 3, 14050 Berlin, Germany. Tel.: +49 30 8445 8215; Fax: +49 30 8445 8255; E-mail: [email protected].
Note: [1] These authors contributed equally to this work.
Abstract: Alzheimer's disease (AD) may affect all cell types in the central nervous system. Astrocytes have rarely been investigated in the aged brain and the role of astrocytes in AD is poorly understood. In this study, we used acute brain slices from an amyloid-β overexpressing double transgenic mouse line where astrocytes express the enhanced green fluorescent protein under the control of the glial fibrillary acidic protein promoter. Using the patch-clamp technique, we analyzed cell coupling and glutamate reactivity, two main features of astrocytes, in the living tissue of aged mice in an AD mouse model. We found large astrocytic networks in the aged (20 to 27 months) transgenic animals in the neocortex, but not in the hippocampus. In contrast, coupling was low in all brain regions of aged control mice. We furthermore noticed significant changes in the responses of astrocytes to glutamate. The expression of functional glutamate transporters and AMPA/kainate-type glutamate receptors increases in the amyloid-β protein precursor overexpressing mice. Thus, exposure to amyloid-β leads to altered astrocyte properties and this change might be beneficial to maintain synaptic function.
