Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus

[Display omitted] Evidence suggests that the stress hormones glucocorticoids (GCs) can cause cognitive deficits and neurodegeneration. Previous studies have found GCs facilitate physiological synapse weakening, termed long-term depression (LTD), though the precise mechanisms underlying this are poor...

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Bibliographic Details
Published in:Pharmacological research 2017-07, Vol.121, p.42-51
Main Authors: Yi, Jee Hyun, Brown, Christopher, Whitehead, Garry, Piers, Thomas, Lee, Young Seok, Perez, Celia Martinez, Regan, Philip, Whitcomb, Daniel J., Cho, Kwangwook
Format: Article
Language:English
Subjects:
Animals
Glucocorticoids
Glucocorticoids - metabolism
Glycogen Synthase Kinase 3 - metabolism
GSK-3
Hippocampus - physiology
Long-Term Potentiation
Phosphorylation
Rats
Signal Transduction
Synapses - physiology
Tau
tau Proteins - metabolism
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Summary:[Display omitted] Evidence suggests that the stress hormones glucocorticoids (GCs) can cause cognitive deficits and neurodegeneration. Previous studies have found GCs facilitate physiological synapse weakening, termed long-term depression (LTD), though the precise mechanisms underlying this are poorly understood. Here we show that GCs activate glycogen synthase kinase-3 (GSK-3), a kinase crucial to synapse weakening signals. Critically, this ultimately leads to phosphorylation of the microtubule associated protein tau, specifically at the serine 396 residue, and this is a causal factor in the GC-mediated impairment of synaptic function. These findings reveal the link between GCs and synapse weakening signals, and the potential for stress-induced priming of neurodegeneration. This could have important implications for our understanding of how stress can lead to neurodegenerative disease.
ISSN:1043-6618
1096-1186
DOI:10.1016/j.phrs.2017.04.015