Susceptibility to ABO and TBOA of LTD and extrasynaptic NMDAR-dependent tonic current in the aged rat hippocampus

Patrick Dutar (1) , B Potier (1)

1 LAC - Laboratoire Aimé Cotton

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  (Ao), one of the AD related synaptotoxic protein species. In this study, we asked for the effects of Ao 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. Ao 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 ao.

Mots clés: Aging; tonic current; extracellular glutamate; synaptic plasticity; NMDA receptors; Alzheimer

Domaines: Neurosciences [q-bio.NC]; Neurobiologie

Patrick Dutar, B Potier. Susceptibility to ABO and TBOA of LTD and extrasynaptic NMDAR-dependent tonic current in the aged rat hippocampus. Neurochemical Research, 2019, 44 (3), pp.692-702. ⟨10.1007/s11064-018-2677-6⟩. ⟨hal-03318632⟩