Rescue of impaired late-phase long-term depression in a tau transgenic mouse model

Tariq Ahmed, David Blum, Sylvie Burnouf, Dominique Demeyer, Valérie Buée-Scherrer, Rudi D'Hooge, Luc Buée, Detlef Balschun

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Cognitive decline, the hallmark of Alzheimer's disease, and accompanying neuropsychiatric symptoms share dysfunctions of synaptic processes as a common cellular pathomechanism. Long-term potentiation has proven to be a sensitive tool for the "diagnosis" of such synaptic dysfunctions. Much less, however, is known about how long-term depression (LTD), an alternative mechanism for the storage of memory, is affected by Alzheimer's disease progression. Here, we demonstrate that impaired late LTD (>3hours) in THY-Tau22 mice can be rescued by either inhibition of glycogen synthase kinase-3 (GSK3β) activity or by application of the protein-phosphatase 2A agonist selenate. In line with these findings, we observed increased phosphorylation of GSK3β at Y216 and reduced total phosphatase activity in biochemical assays of hippocampal tissue of THY-Tau22 mice. Interestingly, LTD induction and pharmacologic inhibition of GSK3β appeared to downregulate GSK3ß activity via a marked upregulation of phosphorylation at the inhibitory Ser9 residue. Our results point to alterations in phosphorylation and/or dephosphorylation homeostasis as key mechanisms underlying the deficits in LTD and hippocampus-dependent learning found in THY-Tau22 mice.

Original languageEnglish
Pages (from-to)730-739
Number of pages10
JournalNeurobiology of Aging
Volume36
Issue number2
DOIs
Publication statusPublished - 1 Feb 2015
Externally publishedYes

    Fingerprint

Keywords

  • Alzheimer's disease
  • CA1-region
  • Glycogen synthase kinase-3
  • Hippocampus
  • Long-term depression
  • LTD
  • Okadaic acid
  • Protein-phosphatase 2A
  • SB216763
  • Sodium selenate
  • Synaptic plasticity
  • Tauopathy

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Ahmed, T., Blum, D., Burnouf, S., Demeyer, D., Buée-Scherrer, V., D'Hooge, R., Buée, L., & Balschun, D. (2015). Rescue of impaired late-phase long-term depression in a tau transgenic mouse model. Neurobiology of Aging, 36(2), 730-739. https://doi.org/10.1016/j.neurobiolaging.2014.09.015