Involvement of the septo-hippocampal cholinergic pathway in association with septal acetylcholinesterase upregulation in a mouse model of tauopathy

Yuko Hara, Yumiko Motoi, Keigo Hikishima, Hiroshi Mizuma, Hirotaka Onoe, Shin Ei Matsumoto, Montasir Elahi, Hideyuki Okano, Shigeki Aoki, Nobutaka Hattori

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Background: Cholinergic cell loss in the basal forebrain, the major source of hippocampal cholinergic projections, has been implicated in Alzheimer’s disease. Objective: To examine whether the septohippocampal pathway is involved in tauopathy model mice and to elucidate the tau-associated mechanism underlying cholinergic alteration. Methods: Adult (6 to 8 months old) and old (16 to 18 months old) transgenic mice expressing wild-type human tau, Tg601, were examined using Ex vivo diffusion tensor magnetic resonance imaging (DTI) and 2-[18F]fluoro- 2-deoxy-D-glucose positron emission tomography (FDG-PET). Choline acetyltransferase (ChAT)-positive neurons in the medial septum (MS) were counted by stereological methods. Acetylcholinesterase (AChE) activity and AChE mRNA in 6 brain regions were measured. Results: Ex vivo DTI revealed that the number of fractional anisotropy (FA) streamlines in the septohippocampal tract decreased with age in Tg601 mice. The FA value in the septum was lower in old Tg601 mice than in non-tg mice. A voxel-based statistical analysis of FDG-PET revealed the presence of low glucose uptake areas, involving the MS in adults, and spread over regions including the hippocampal dentate gyrus in old mice. In the MS, the number of choline acetyltransferase (ChAT)-positive neurons decreased in old Tg601 mice. AChE activity and AChE mRNA T transcripts were exclusively higher in the septum. Conclusion: The upregulation of AChE in the septum may result in the selective degeneration of the septohippocampal cholinergic pathway in the tauopathy mouse model.

Original languageEnglish
Pages (from-to)94-103
Number of pages10
JournalCurrent Alzheimer Research
Issue number1
Publication statusPublished - 2017 Jan 1



  • Acetylcholinesterase
  • Choline acetyltransferase
  • Diffusion tensor imaging
  • PET
  • Septo-hippocampal pathway
  • Tau

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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