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

Identification of an acute functional cross-talk between amyloid-β and glucocorticoid receptors at hippocampal excitatory synapses. Neurobiol Dis. 2018 Jul 09;: Authors: Kootar S, Frandemiche ML, Dhib G, Mouska X, Lorivel T, Poupon-Silvestre G, Hunt H, Tronche F, Bethus I, Barik J, Marie H 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) increase 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 b...
Source: Neurobiology of Disease - Category: Neurology Authors: Tags: Neurobiol Dis Source Type: research