Involvement of hippocampal excitability in amyloid β-induced behavioral and psychological symptoms of dementia

J Toxicol Sci. 2016;41(4):449-57. doi: 10.2131/jts.41.449.


In patients with Alzheimer's disease, in addition to the core symptoms, i.e., cognitive dysfunction, behavioral and psychological symptoms of dementia (BPSD) such as aggression, anxiety, and hallucinations are known to occur frequently. Because various environmental factors influence the onset and progression of Alzheimer's disease, in the present study, BPSD-like behavioral abnormality of Amyloid β (Aβ)1-42-injected mice was assessed under social isolation, which induces behavioral abnormality. Aβ protein (500 pmol) was injected into the lateral ventricle of mice, which were individually housed. Two and three weeks after injection into adult mice, the rate of mice that exhibited aggressive behavior, i.e., biting attacks and wrestling, to the total mice, was markedly increased by Aβ injection. Aβ-injected adult mice also showed anxiety-like behavior, in addition to cognitive decline. Serum corticosterone level was markedly increased by Aβ injection. When excitability of hippocampal neurons was checked using hippocampal slices, KCl-induced presynaptic activity was enhanced in hippocampal slices prepared from Aβ-injected mice. These results suggest that social isolation housing of Aβ1-42-injected adult mice induces BPSD-like behavioral abnormality in addition to cognitive decline. It is likely that behavioral abnormality of Aβ1-42-injected adult mice is associated with excitability of hippocampal glutamatergic neurons, which is associated with the elevated corticosterone level.

MeSH terms

  • Aggression
  • Alzheimer Disease / chemically induced
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / physiopathology*
  • Alzheimer Disease / psychology*
  • Amyloid beta-Peptides*
  • Animals
  • Anxiety / chemically induced
  • Anxiety / physiopathology
  • Anxiety / psychology
  • Behavior, Animal*
  • Cognition
  • Cognition Disorders / chemically induced
  • Cognition Disorders / physiopathology
  • Cognition Disorders / psychology
  • Corticosterone / blood
  • Disease Models, Animal
  • Glutamic Acid / metabolism
  • Hippocampus / metabolism
  • Hippocampus / physiopathology*
  • Housing, Animal
  • In Vitro Techniques
  • Male
  • Maze Learning
  • Mice
  • Motor Activity
  • Peptide Fragments*
  • Recognition, Psychology
  • Social Isolation
  • Synaptic Transmission
  • Time Factors


  • Amyloid beta-Peptides
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • Glutamic Acid
  • Corticosterone