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Article

Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics

1
Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka 238-8580, Japan
2
Institute for Advanced Biosciences, Keio University, Tsuruoka 708-0813, Japan
3
Health Promotion and Preemptive Medicine, Research and Development Center for Minimally Invasive Therapies, Tokyo Medical University, Tokyo 160-8402, Japan
4
Department of Dental Hygiene, Junior College, Kanagawa Dental University, Yokosuka 238-8580, Japan
*
Author to whom correspondence should be addressed.
Academic Editors: Daniele Orsucci and Glòria Garrabou
J. Clin. Med. 2021, 10(8), 1698; https://doi.org/10.3390/jcm10081698
Received: 24 February 2021 / Revised: 11 March 2021 / Accepted: 13 April 2021 / Published: 15 April 2021
(This article belongs to the Special Issue Metabolomic Analysis in Health and Disease)
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. View Full-Text
Keywords: dementia; cognitive impairment; cerebrovascular disease; saliva; metabolomics; BDNF dementia; cognitive impairment; cerebrovascular disease; saliva; metabolomics; BDNF
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MDPI and ACS Style

To, M.; Sugimoto, M.; Saruta, J.; Yamamoto, Y.; Sakaguchi, W.; Kawata, A.; Matsuo, M.; Tsukinoki, K. Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics. J. Clin. Med. 2021, 10, 1698. https://doi.org/10.3390/jcm10081698

AMA Style

To M, Sugimoto M, Saruta J, Yamamoto Y, Sakaguchi W, Kawata A, Matsuo M, Tsukinoki K. Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics. Journal of Clinical Medicine. 2021; 10(8):1698. https://doi.org/10.3390/jcm10081698

Chicago/Turabian Style

To, Masahiro, Masahiro Sugimoto, Juri Saruta, Yuko Yamamoto, Wakako Sakaguchi, Akira Kawata, Masato Matsuo, and Keiichi Tsukinoki. 2021. "Cognitive Dysfunction in a Mouse Model of Cerebral Ischemia Influences Salivary Metabolomics" Journal of Clinical Medicine 10, no. 8: 1698. https://doi.org/10.3390/jcm10081698

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