title: Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice.
abstract: Mutant R406W human tau was originally identified in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and causes a hereditary tauopathy that clinically resembles Alzheimer's disease (AD). In the current study, we examined the performance of R406W transgenic (Tg) mice in the forced swimming test, a test with high predictivity of antidepressant efficacy in human depression, and found an enhancement of the immobility time. In contrast, the motor function and anxiety-related emotional response of R406W Tg mice were normal. Furthermore, a selective serotonin reuptake inhibitor (SSRI), fluvoxamine (100 mg/kg, p.o.), significantly reduced this enhancement of the immobility time, whereas a noradrenaline reuptake inhibitor, desipramine, had no effect. In an in vivo microdialysis study, R406W Tg mice exhibited a significantly decreased extracellular 5-hydroxyindoleacetic acid (5-HIAA) level in the frontal cortex and also exhibited a tendency toward a decreased extracellular 5-hydroxytryptamine (5-HT) level. Moreover, fluvoxamine, which reduced the enhancement of the immobility time, significantly increased the extracellular 5-HT level in R406W Tg mice. These results suggest that R406W Tg mice exhibit changes in depression-related behavior involving serotonergic neurons and provide an animal model for investigating AD with depression.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, Fukuoka 814-0180, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
authors.forename: Takuya
authors.initials: T
authors.lastname: Watanabe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kawabe
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuda
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Shozo
authors.initials: S
authors.lastname: Chidori
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001923:Brain Chemistry / Q000235:genetics; D003866:Depressive Disorder / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D004195:Disease Models, Animal; D045604:Extracellular Fluid / Q000378:metabolism; D016666:Fluvoxamine / Q000494:pharmacology; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D017551:Microdialysis; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000378:metabolism*; D011903:Raphe Nuclei / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013550:Swimming / Q000523:psychology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D016875:tau Proteins / Q000235:genetics*
chemical_list: D016666:Fluvoxamine; D006897:Hydroxyindoleacetic Acid; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors; D016875:tau Proteins