Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission

Ann Van der Jeugd, Tariq Ahmed, Sylvie Burnouf, Karim Belarbi, Malika Hamdame, Marie Eve Grosjean, Sandrine Humez, Detlef Balschun, David Blum, Luc Buée, Rudi D'Hooge

Research output: Contribution to journalArticle

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Abstract

We evaluated various forms of hippocampus-dependent learning and memory, and hippocampal synaptic plasticity in THY-Tau22 transgenic mice, a murine tauopathy model that expresses double-mutated 4-repeat human tau, and shows neuropathological tau hyperphosphorylation and aggregation throughout the brain. Focussing on hippocampus, immunohistochemical studies in aged THY-Tau22 mice revealed prominent hyper- and abnormal phosphorylation of tau in CA1 region, and an increase in glial fibrillary acidic protein (GFAP) in hippocampus, but without signs of neuronal loss. These mice displayed spatial, social, and contextual learning and memory defects that could not be reduced to subtle neuromotor disability. The behavioral defects coincided with changes in hippocampal synaptic functioning and plasticity as measured in paired-pulse and novel long-term depression protocols. These results indicate that hippocampal tauopathy without neuronal cell loss can impair neural and behavioral plasticity, and further show that transgenic mice, such as the THY-Tau22 strain, might be useful for preclinical research on tauopathy pathogenesis and possible treatment.

Original languageEnglish
Pages (from-to)296-304
Number of pages9
JournalNeurobiology of Learning and Memory
Volume95
Issue number3
DOIs
Publication statusPublished - Mar 2011
Externally publishedYes

Fingerprint

Tauopathies
Neuronal Plasticity
Synaptic Transmission
Transgenic Mice
Hippocampus
Learning
Glial Fibrillary Acidic Protein
Phosphorylation
Depression
Brain
Research

Keywords

  • Alzheimer's disease
  • Hippocampus
  • Learning and memory
  • Long-term depression
  • Synaptic plasticity
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

Cite this

Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. / Jeugd, Ann Van der; Ahmed, Tariq; Burnouf, Sylvie; Belarbi, Karim; Hamdame, Malika; Grosjean, Marie Eve; Humez, Sandrine; Balschun, Detlef; Blum, David; Buée, Luc; D'Hooge, Rudi.

In: Neurobiology of Learning and Memory, Vol. 95, No. 3, 03.2011, p. 296-304.

Research output: Contribution to journalArticle

Jeugd, Ann Van der ; Ahmed, Tariq ; Burnouf, Sylvie ; Belarbi, Karim ; Hamdame, Malika ; Grosjean, Marie Eve ; Humez, Sandrine ; Balschun, Detlef ; Blum, David ; Buée, Luc ; D'Hooge, Rudi. / Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission. In: Neurobiology of Learning and Memory. 2011 ; Vol. 95, No. 3. pp. 296-304.
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