Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease

Takuya Watanabe, Norito Yamagata, Kotaro Takasaki, Kazunori Sano, Kazuhide Hayakawa, Shutaro Katsurabayashi, Nobuaki Egashira, Kenichi Mishima, Katsunori Iwasaki, Michihiro Fujiwara

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Abstract

Acetylcholine (ACh) release is one of the key factors in memory mechanisms. To clarify whether beta-amyloid (Aβ) induces a disturbance of the cholinergic system leading to memory impairment, we examined memory impairment and measured hippocampal ACh release in Tg2576 (Tg) mice that over-express the Swedish mutant amyloid precursor protein (APPsw). Furthermore, we examined Aβ burden with aging. Tg mice aged 9-11 months, but not aged 4-6 months, showed memory impairment in the 8-arm radial maze behavior test. Spontaneous ACh release was not altered in Tg mice compared with age-matched control mice at 4-6 or 9-11 months of age. On the other hand, high-K+-evoked ACh release was decreased in Tg mice aged 9-11 months, but not in Tg mice aged 4-6 months. Hippocampal Aβ increased in an age-dependent manner, but evident amyloid plaques were not found in the hippocampus of Tg mice aged 11 months. These results suggest that memory impairment in Tg mice could be attributed to cholinergic synapse dysfunction that could not be caused predominantly by amyloid plaques. Measuring ACh release in this model might be a useful index for the screening of new drugs to treat the early-phase of Alzheimer's disease.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalBrain Research
Volume1249
DOIs
Publication statusPublished - Jan 16 2009
Externally publishedYes

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All Science Journal Classification (ASJC) codes

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

Cite this

Watanabe, T., Yamagata, N., Takasaki, K., Sano, K., Hayakawa, K., Katsurabayashi, S., ... Fujiwara, M. (2009). Decreased acetylcholine release is correlated to memory impairment in the Tg2576 transgenic mouse model of Alzheimer's disease. Brain Research, 1249, 222-228. https://doi.org/10.1016/j.brainres.2008.10.029