Altered depression-related behavior and neurochemical changes in serotonergic neurons in mutant R406W human tau transgenic mice

Nobuaki Egashira, Katsunori Iwasaki, Akihiko Takashima, Takuya Watanabe, Hideyuki Kawabe, Tomomi Matsuda, Kenichi Mishima, Shozo Chidori, Ryoji Nishimura, Michihiro Fujiwara

Research output: Contribution to journalArticlepeer-review

37 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)7-12
Number of pages6
JournalBrain Research
Volume1059
Issue number1
DOIs
Publication statusPublished - Oct 12 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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