title: Hippocampal tauopathy in tau transgenic mice coincides with impaired hippocampus-dependent learning and memory, and attenuated late-phase long-term depression of synaptic transmission.
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.
authors.affiliation: Laboratory of Biological Psychology, Department of Psychology, Catholic University of Leuven, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Van der Jeugd
authors.forename: Tariq
authors.initials: T
authors.lastname: Ahmed
authors.forename: Sylvie
authors.initials: S
authors.lastname: Burnouf
authors.forename: Karim
authors.initials: K
authors.lastname: Belarbi
authors.forename: Malika
authors.initials: M
authors.lastname: Hamdame
authors.forename: Marie-Eve
authors.initials: ME
authors.lastname: Grosjean
authors.forename: Sandrine
authors.initials: S
authors.lastname: Humez
authors.forename: Detlef
authors.initials: D
authors.lastname: Balschun
authors.forename: David
authors.initials: D
authors.lastname: Blum
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.forename: Rudi
authors.initials: R
authors.lastname: D'Hooge
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D003214:Conditioning, Classical / Q000502:physiology; D004195:Disease Models, Animal; D005239:Fear; D005518:Food Preferences; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D007150:Immunohistochemistry; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010766:Phosphorylation; D012919:Social Behavior; D024801:Tauopathies / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016875:tau Proteins