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

Jee Hyun Yi, Christopher Martin Brown, Garry Whitehead, Thomas Piers, Young Seok Lee, Celia Perez, Philip Regan, Daniel Whitcomb, Kwangwook Cho

Research output: Contribution to journalArticlepeer-review

16 Downloads (Pure)


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.
Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalPharmacological Research
Early online date14 Apr 2017
Publication statusPublished - 1 Jul 2017
Externally publishedYes


  • Glucocorticoids
  • GSK-3
  • Tau
  • Long-term potentiation


Dive into the research topics of 'Glucocorticoids activate a synapse weakening pathway culminating in tau phosphorylation in the hippocampus'. Together they form a unique fingerprint.

Cite this