title: Differential regional distribution of phosphorylated tau and synapse loss in the nucleus accumbens in tauopathy model mice.
abstract: Tauopathies differ in terms of the brain regions that are affected. In Alzheimer's disease, basal forebrain and hippocampus are mainly involved, while frontotemporal lobar degeneration affects the frontal and temporal lobes and subcortical nuclei including striatum. Over 90% of human cases of tauopathies are sporadic, although the majority of established tau-transgenic mice have had mutations. This prompted us to establish transgenic mice expressing wild-type human tau (Tg601). Old (>14 months old) Tg601 mice displayed decreased anxiety in the elevated plus maze test and impaired place learning in the Morris water maze test. Immunoblotting of brain tissue identified that soluble tau multimer was increased with aging even though insoluble tau was not observed. In the striatum of old Tg601, the level of AT8- or AT180-positive tau was decreased compared with that of other regions, while PHF-1-positive tau levels remained equal. Phosphorylated tau-positive axonal dilations were present mainly in layers V and VI of the prefrontal cortex. Loss of synaptic dendritic spine and decreased immunohistochemical level of synaptic markers were observed in the nucleus accumbens. In vivo 2-[(18)F]fluoro-2-deoxy-d-glucose positron emission tomography analysis also showed decreased activity exclusively in the nucleus accumbens of living Tg601 mice. In Tg601 mice, the axonal transport defect in the prefrontal cortex-nucleus accumbens pathway may lead to decreased anxiety behavior. Differential distribution of hyperphosphorylated tau may cause region-specific neurodegeneration.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Taiki
authors.initials: T
authors.lastname: Kambe
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Motoi
authors.forename: Ran
authors.initials: R
authors.lastname: Inoue
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kojima
authors.forename: Norihiro
authors.initials: N
authors.lastname: Tada
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kimura
authors.forename: Naruhiko
authors.initials: N
authors.lastname: Sahara
authors.forename: Shunji
authors.initials: S
authors.lastname: Yamashita
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Mizoroki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: Kohei
authors.initials: K
authors.lastname: Shimada
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizuma
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Onoe
authors.forename: Yoshikuni
authors.initials: Y
authors.lastname: Mizuno
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology; D016874:Neurofibrillary Tangles / Q000378:metabolism / Q000473:pathology; D009714:Nucleus Accumbens / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D049268:Positron-Emission Tomography; D013569:Synapses / Q000378:metabolism* / Q000473:pathology; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology; D014018:Tissue Distribution; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins