Abstract
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.
Highlights
Dementia is a progressive neurodegenerative disease that causes cognitive impairment in older people
We have demonstrated that brain function, hippocampal brain-derived neurotrophic factor (BDNF), and GAD1GABA signaling influence salivary BDNF levels in transgenic mice [36]
These results suggest that spatial memory was impaired by cerebral ischemia and that tacrine administration ameliorated this deficit
Summary
Dementia is a progressive neurodegenerative disease that causes cognitive impairment in older people. Multiple diagnostic criteria for VaD, as well as for its subtypes, are required to diagnose cognitive impairment [4]. This manifestation is induced by infarcts and atrophy in the brain, and coexistence with Alzheimer’s disease is frequent [3]. The pathogenic mechanism of VaD has been investigated in animal models [6], established using cerebral hypoperfusion [2,7]. To further elucidate the pathobiology of VaD, many studies have used a cerebral ischemia model [6,9], which has provided evidence of the utility of neuroprotective agents in the brain [9]. Few studies have investigated diagnostic biomarkers for a cerebral ischemia animal model
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