Cognitive dysfunction in a mouse model of cerebral ischemia influences salivary metabolomics

Masahiro To, Masahiro Sugimoto, Juri Saruta, Yuko Yamamoto, Wakako Sakaguchi, Akira Kawata, Masato Matsuo, Keiichi Tsukinoki

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


Vascular dementia, caused by cerebrovascular disease, is associated with cognitive impairment and reduced hippocampal metabolite levels. Specifically, cognitive impairment can be induced by decreased hippocampal brain-derived neurotrophic factor (BDNF) expression. The development of low or non-invasive biomarkers to characterize these diseases is an urgent task. Disturbance of metabolic pathways has been frequently observed in cognitive impairment, and salivary molecules also showed the potentials to reflect cognitive impairment. Therefore, we evaluated salivary metabolic profiles associated with altered hippocampal BDNF expression levels in a cerebral ischemia mouse model using metabolomic analyses. The effect of tacrine (a cholinesterase inhibitor) administration was also examined. The arteries of ICR mice were occluded with aneurysm clips to generate the cerebral ischemia model. Learning and memory performance was assessed using the elevated plus maze (EPM) test. Hippocampal and blood BDNF levels were quantified using an enzyme-linked immunosorbent assay. Glutamate decarboxylase 1 (GAD1) mRNA expression, is associated with cognitive impairment, was quantified by a real-time polymerase chain reaction. The EPM test revealed impaired spatial working memory in the cerebral ischemia mouse model; tacrine administration ameliorated this memory impairment. Cerebral ischemia suppressed GAD1 expression by decreasing hippocampal BDNF expression. In total, seven salivary metabolites, such as trimethylamine N-oxide and putrescine, were changed by cognitive impairment and tacrine administration. Our data suggest that salivary metabolite patterns were associated with cognitive function.

Original languageEnglish
Article number1698
JournalJournal of Clinical Medicine
Issue number8
Publication statusPublished - 2021 Apr 2


  • BDNF
  • Cerebrovascular disease
  • Cognitive impairment
  • Dementia
  • Metabolomics
  • Saliva

ASJC Scopus subject areas

  • General Medicine


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