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

17 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

Glycogen Synthase Kinase 3
Transgenic Mice
Depression
Phosphorylation
Alzheimer Disease
Selenic Acid
Protein Phosphatase 2
Long-Term Potentiation
Phosphoric Monoester Hydrolases
Disease Progression
Hippocampus
Homeostasis
Up-Regulation
Down-Regulation
Learning
Inhibition (Psychology)

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., ... 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

Rescue of impaired late-phase long-term depression in a tau transgenic mouse model. / Ahmed, Tariq; Blum, David; Burnouf, Sylvie; Demeyer, Dominique; Buée-Scherrer, Valérie; D'Hooge, Rudi; Buée, Luc; Balschun, Detlef.

In: Neurobiology of Aging, Vol. 36, No. 2, 01.02.2015, p. 730-739.

Research output: Contribution to journalArticle

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, vol. 36, no. 2, pp. 730-739. https://doi.org/10.1016/j.neurobiolaging.2014.09.015
Ahmed, Tariq ; Blum, David ; Burnouf, Sylvie ; Demeyer, Dominique ; Buée-Scherrer, Valérie ; D'Hooge, Rudi ; Buée, Luc ; Balschun, Detlef. / Rescue of impaired late-phase long-term depression in a tau transgenic mouse model. In: Neurobiology of Aging. 2015 ; Vol. 36, No. 2. pp. 730-739.
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