| First Author | Kootar S | Year | 2018 |
| Journal | Neurobiol Dis | Volume | 118 |
| Pages | 117-128 | PubMed ID | 30003950 |
| Mgi Jnum | J:268314 | Mgi Id | MGI:6267094 |
| Doi | 10.1016/j.nbd.2018.07.001 | Citation | Kootar S, et al. (2018) Identification of an acute functional cross-talk between amyloid-beta and glucocorticoid receptors at hippocampal excitatory synapses. Neurobiol Dis 118:117-128 |
| abstractText | Amyloid-beta 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-beta (Abetaomicron) is now believed to represent the main Amyloid-beta species affecting synapse function. Yet, the exact molecular mechanism by which Abetaomicron modifies synapse function remains to be fully elucidated. There is accumulating evidence that glucocorticoid receptors (GRs) might participate in Abetaomicron generation and activity in the brain. Here, we provide evidence for an acute functional cross-talk between Abeta 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 Abetao (100nM) increases GR levels in spines and PSD. Also, in these cultured neurons, blocking GRs with two different GR antagonists prevents Abetao-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 Abetao-mediated LTP impairment, but not Abetao-mediated LTD induction. The necessity of neuronal GRs for Abetao-mediated LTP was confirmed by genetically removing GRs in vivo from CA1 neurons using conditional GR mutant mice. These results indicate a tight functional interplay between GR and Abeta activities at excitatory synapses. |
