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Susceptibility to Aβo and TBOA of LTD and Extrasynaptic NMDAR-Dependent Tonic Current in the Aged Rat Hippocampus

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Abstract

Aging, as the major risk factor of Alzheimer’s disease (AD), may increase susceptibility to neurodegenerative diseases through many gradual molecular and biochemical changes. Extracellular glutamate homeostasis and extrasynaptic glutamate N-methyl-D-aspartate receptors (NMDAR) are among early synaptic targets of oligomeric amyloid β (Aβo), one of the AD related synaptotoxic protein species. In this study, we asked for the effects of Aβo on long-term depression (LTD), a form of synaptic plasticity dependent on extrasynaptic NMDAR activation, and on a tonic current (TC) resulting from the activation of extrasynaptic NMDAR by ambient glutamate in hippocampal slices from young (3–6-month-old) and aged (24–28-month-old) Sprague–Dawley rats. Aβo significantly enhanced the magnitude of LTD and the amplitude of TC in aged slices compared to young ones. TBOA, a glutamate transporter inhibitor, also significantly increased LTD magnitude and TC amplitude in slices from aged rats, suggesting either an age-related weakness of the glutamate clearance system and/or a facilitated extrasynaptic NMDAR activation. From our present data, we hypothesize that senescence-related impairment of the extrasynaptic environment may be a vector of vulnerability of the aged hippocampus to neurodegenerative promotors such as Aβo.

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Acknowledgements

This work was supported in part by INSERM. The authors are grateful to the animal caretakers of the CPN.

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  1. Patrick Dutar & Brigitte Potier

    Present address: Laboratoire Aimé Cotton, ENS-Cachan, CNRS, Univ. Paris-Sud, Université Paris-Saclay, 91405, Orsay, France

Authors and Affiliations

  1. Centre de Psychiatrie et de Neurosciences, INSERM U894, Université Paris-Descartes, 102 rue la Santé, 75014, Paris, France

    Patrick Dutar & Brigitte Potier

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Correspondence to Brigitte Potier.

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Special issue: In honor of Graham Collingridge

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Dutar, P., Potier, B. Susceptibility to Aβo and TBOA of LTD and Extrasynaptic NMDAR-Dependent Tonic Current in the Aged Rat Hippocampus. Neurochem Res 44, 692–702 (2019). https://doi.org/10.1007/s11064-018-2677-6

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  • DOI: https://doi.org/10.1007/s11064-018-2677-6

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