Identification of an acute functional cross-talk between amyloid-β and glucocorticoid receptors at hippocampal excitatory synapses

Neurobiology of Disease
Scherazad KootarHélène Marie

Abstract

Amyloid-β is a peptide released by synapses in physiological conditions and its pathological accumulation in brain structures necessary for memory processing represents a key toxic hallmark underlying Alzheimer's disease. The oligomeric form of Amyloid-β (Aβο) is now believed to represent the main Amyloid-β species affecting synapse function. Yet, the exact molecular mechanism by which Aβο modifies synapse function remains to be fully elucidated. There is accumulating evidence that glucocorticoid receptors (GRs) might participate in Aβο generation and activity in the brain. Here, we provide evidence for an acute functional cross-talk between Aβ and GRs at hippocampal excitatory synapses. Using live imaging and biochemical analysis of post-synaptic densities (PSD) in cultured hippocampal neurons, we show that synthetic Aβo (100 nM) increases GR levels in spines and PSD. Also, in these cultured neurons, blocking GRs with two different GR antagonists prevents Aβo-mediated PSD95 increase within the PSD. By analyzing long-term potentiation (LTP) and long-term depression (LTD) in ex vivo hippocampal slices after pharmacologically blocking GR, we also show that GR signaling is necessary for Aβo-mediated LTP impairment, but not Aβo-med...Continue Reading

Citations

Apr 5, 2020·International Journal of Molecular Sciences·Alejandro F De NicolaMaria Claudia Gonzalez Deniselle
Aug 26, 2020·Alzheimer's Research & Therapy·Amira Latif-HernandezDetlef Balschun
Jul 1, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Yingjie QiMichael J Rowan

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