Decreased level of brain acetylcholine and memory disturbance in APPsw mice

Yasushi Ikarashi, Yasuo Harigaya, Yasushi Tomidokoro, Mitsuyasu Kanai, Masaki Ikeda, Etsuro Matsubara, Takeshi Kawarabayashi, Hisashi Kuribara, Steven G. Younkin, Yuji Maruyama, Mikio Shoji

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

To clarify whether amyloid β protein (Aβ) amyloidosis induces a disturbance of cholinergic system leading to long-term memory deficits, we continuously examined memory disturbance using the passive-avoidance task, and measured Aβ burden and concentrations of acetylcholine in the brain of APPsw transgenic mice. Repetitive retention trials of the passive-avoidance task showed that the long-term memory impairment in APPsw mice appeared from ∼7.75 months old and progressively advanced. Significant decreases in acetylcholine levels were found in the brains of 10-month-old mice. A few senile plaques appeared in the cerebral cortex and the hippocampus at 8 months old, and increased in size and number with aging. The concentrations of brain Aβ40/42(43) gradually increased from 8 months old and exponentially increased thereafter. Advance of long-term memory disturbance was closely correlated with Aβ40/42(43) burden. These findings suggested that Aβ accumulation induced long-term memory impairment and disturbance of the cholinergic system, and that the passive-avoidance task and measuring acetylcholine were useful methods for evaluating this mouse model as well as Aβ accumulation.

Original languageEnglish (US)
Pages (from-to)483-490
Number of pages8
JournalNeurobiology of aging
Volume25
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • APPsw mice
  • Acetylcholine
  • Alzheimer's disease
  • Long-term memory
  • Passive-avoidance task

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

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