{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T11:38:34Z","timestamp":1793014714748,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T00:00:00Z","timestamp":1506038400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,9,22]],"date-time":"2017-09-22T00:00:00Z","timestamp":1506038400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A high-fat (HF) diet alters gut microbiota and promotes obesity related inflammation and cognitive impairment. Teasaponin is the major active component of tea, and has been associated with anti-inflammatory effects and improved microbiota composition. However, the potential protective effects of teasaponin, against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, obesity was induced in C57BL\/6\u2009J male mice by feeding a HF diet for 8 weeks, followed by treatment with oral teasaponin (0.5%) mixed in HF diet for a further 6 weeks. Teasaponin treatment prevented the HF diet-induced recognition memory impairment and improved neuroinflammation, gliosis and brain-derived neurotrophic factor (BDNF) deficits in the hippocampus. Furthermore, teasaponin attenuated the HF diet-induced endotoxemia, pro-inflammatory macrophage accumulation in the colon and gut microbiota alterations. Teasaponin also improved glucose tolerance and reduced body weight gain in HF diet-induced obese mice. The behavioral and neurochemical improvements suggest that teasaponin could limit unfavorable gut microbiota alterations and cognitive decline in HF diet-induced obesity.<\/jats:p>","DOI":"10.1038\/s41598-017-12156-2","type":"journal-article","created":{"date-parts":[[2017,9,18]],"date-time":"2017-09-18T13:55:18Z","timestamp":1505742918000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Dietary teasaponin ameliorates alteration of gut microbiota and cognitive decline in diet-induced obese mice"],"prefix":"10.1038","volume":"7","author":[{"given":"Sen","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5895-2253","authenticated-orcid":false,"given":"Xu-Feng","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly A.","family":"Newell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongqin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuiyang","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinghua","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,9,22]]},"reference":[{"key":"12156_CR1","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1172\/JCI10842","volume":"106","author":"BB Kahn","year":"2000","unstructured":"Kahn, B. B. & Flier, J. S. Obesity and insulin resistance. J Clin Invest \n                           106, 473\u201381 (2000).","journal-title":"J Clin Invest"},{"key":"12156_CR2","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1212\/WNL.0b013e3182661f63","volume":"79","author":"A Singh-Manoux","year":"2012","unstructured":"Singh-Manoux, A. et al. Obesity phenotypes in midlife and cognition in early old age: the Whitehall II cohort study. Neurology \n                           79, 755\u201362 (2012).","journal-title":"Neurology"},{"key":"12156_CR3","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1038\/526312a","volume":"526","author":"PA Smith","year":"2015","unstructured":"Smith, P. A. The tantalizing links between gut microbes and the brain. Nature \n                           526, 312\u20134 (2015).","journal-title":"Nature"},{"key":"12156_CR4","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.chom.2008.02.015","volume":"3","author":"PJ Turnbaugh","year":"2008","unstructured":"Turnbaugh, P. J., B\u00e4ckhed, F., Fulton, L. & Gordon, J. I. Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome. Cell Host Microbe \n                           3, 213\u201323 (2008).","journal-title":"Cell Host Microbe"},{"key":"12156_CR5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.pnpbp.2015.01.004","volume":"59","author":"D Camer","year":"2015","unstructured":"Camer, D. et al. Bardoxolone methyl prevents high-fat diet-induced alterations in prefrontal cortex signalling molecules involved in recognition memory. Prog Neuropsychopharmacol Biol Psychiatry \n                           59, 68\u201375 (2015).","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"12156_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11011-016-9917-8","volume":"32","author":"C Proctor","year":"2017","unstructured":"Proctor, C., Thiennimitr, P., Chattipakorn, N. & Chattipakorn, S. C. Diet, gut microbiota and cognition. Metab Brain Dis \n                           32, 1\u201317 (2017).","journal-title":"Metab Brain Dis"},{"key":"12156_CR7","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-016-0578-7","volume":"13","author":"SN De Luca","year":"2016","unstructured":"De Luca, S. N. et al. Early life overfeeding impairs spatial memory performance by reducing microglial sensitivity to learning. J Neuroinflammation \n                           13, 112 (2016).","journal-title":"J Neuroinflammation"},{"key":"12156_CR8","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.bbr.2014.04.032","volume":"285","author":"V Luine","year":"2015","unstructured":"Luine, V. Recognition memory tasks in neuroendocrine research. Behav Brain Res \n                           285, 158\u201364 (2015).","journal-title":"Behav Brain Res"},{"key":"12156_CR9","doi-asserted-by":"publisher","first-page":"14515","DOI":"10.1073\/pnas.0406344101","volume":"101","author":"NJ Broadbent","year":"2004","unstructured":"Broadbent, N. J., Squire, L. R. & Clark, R. E. Spatial memory, recognition memory, and the hippocampus. Proc Natl Acad Sci USA \n                           101, 14515\u201320 (2004).","journal-title":"Proc Natl Acad Sci USA"},{"key":"12156_CR10","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/j.bbi.2016.03.013","volume":"57","author":"AC Kentner","year":"2016","unstructured":"Kentner, A. C., Khoury, A., Lima Queiroz, E. & MacRae, M. Environmental enrichment rescues the effects of early life inflammation on markers of synaptic transmission and plasticity. Brain Behav Immun \n                           57, 151\u201360 (2016).","journal-title":"Brain Behav Immun"},{"key":"12156_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148328","volume":"11","author":"M Picot","year":"2016","unstructured":"Picot, M. et al. Neural Androgen Receptor Deletion Impairs the Temporal Processing of Objects and Hippocampal CA1-Dependent Mechanisms. PLoS One \n                           11, e0148328 (2016).","journal-title":"PLoS One"},{"key":"12156_CR12","doi-asserted-by":"publisher","first-page":"58","DOI":"10.3945\/ajcn.110.010132","volume":"94","author":"R Jumpertz","year":"2011","unstructured":"Jumpertz, R. et al. Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr \n                           94, 58\u201365 (2011).","journal-title":"Am J Clin Nutr"},{"key":"12156_CR13","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047713","volume":"7","author":"KA Kim","year":"2012","unstructured":"Kim, K. A., Gu, W., Lee, I. A., Joh, E. H. & Kim, D. H. High Fat Diet-Induced Gut Microbiota Exacerbates Inflammation and Obesity in Mice via the TLR4 Signaling Pathway. PLoS One \n                           7, e47713 (2012).","journal-title":"PLoS One"},{"key":"12156_CR14","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nature11550","volume":"489","author":"CA Lozupone","year":"2012","unstructured":"Lozupone, C. A., Stombaugh, J. I., Gordon, J. I., Jansson, J. K. & Knight, R. Diversity, stability and resilience of the human gut microbiota. Nature \n                           489, 220\u201330 (2012).","journal-title":"Nature"},{"key":"12156_CR15","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1111\/jnc.13774","volume":"139","author":"M Podbielska","year":"2016","unstructured":"Podbielska, M. et al. Neuron-microglia interaction induced bi-directional cytotoxicity associated with calpain activation. J Neurochem \n                           139, 440\u2013455 (2016).","journal-title":"J Neurochem"},{"key":"12156_CR16","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1002\/glia.20467","volume":"55","author":"L Qin","year":"2007","unstructured":"Qin, L. et al. Systemic LPS Causes Chronic Neuroinflammation and Progressive Neurodegeneration. Glia \n                           55, 453\u201362 (2007).","journal-title":"Glia"},{"key":"12156_CR17","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/453120","volume":"2008","author":"C Gurley","year":"2008","unstructured":"Gurley, C. et al. Microglia and Astrocyte Activation by Toll-Like Receptor Ligands: Modulation by PPAR-gamma Agonists. PPAR Res \n                           2008, 453120 (2008).","journal-title":"PPAR Res"},{"key":"12156_CR18","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/610343","volume":"2014","author":"A Sierra","year":"2014","unstructured":"Sierra, A. et al. Surveillance, phagocytosis, and inflammation: how never-resting microglia influence adult hippocampal neurogenesis. Neural Plast \n                           2014, 610343 (2014).","journal-title":"Neural Plast"},{"key":"12156_CR19","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1053\/j.gastro.2011.04.052","volume":"141","author":"P Bercik","year":"2011","unstructured":"Bercik, P. et al. The intestinal microbiota affect central levels of brain-derived neurotropic factor and behavior in mice. Gastroenterology \n                           141, 599\u2013609 (2011).","journal-title":"Gastroenterology"},{"key":"12156_CR20","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1002\/mnfr.200500102","volume":"50","author":"S Wolfram","year":"2006","unstructured":"Wolfram, S., Wang, Y. & Thielecke, F. Anti-obesity effects of green tea: from bedside to bench. Mol Nutr Food Res \n                           50, 176\u201387 (2006).","journal-title":"Mol Nutr Food Res"},{"key":"12156_CR21","doi-asserted-by":"publisher","DOI":"10.1186\/1743-7075-9-105","volume":"9","author":"U Axling","year":"2012","unstructured":"Axling, U. et al. Green tea powder and Lactobacillus plantarum affect gut microbiota, lipid metabolism and inflammation in high-fat fed C57BL\/6\u2009J mice. Nutr Metab (Lond) \n                           9, 105 (2012).","journal-title":"Nutr Metab (Lond)"},{"key":"12156_CR22","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1111\/j.1348-0421.2012.00502.x","volume":"56","author":"JS Jin","year":"2012","unstructured":"Jin, J. S., Touyama, M., Hisada, T. & Benno, Y. Effects of green tea consumption on human fecal microbiota with special reference to Bifidobacterium species. Microbiol Immunol \n                           56, 729\u201339 (2012).","journal-title":"Microbiol Immunol"},{"key":"12156_CR23","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1093\/ajcn\/83.2.355","volume":"83","author":"S Kuriyama","year":"2006","unstructured":"Kuriyama, S. et al. Green tea consumption and cognitive function: a cross-sectional study from the Tsurugaya Project 1. Am J Clin Nutr \n                           83, 355\u201361 (2006).","journal-title":"Am J Clin Nutr"},{"key":"12156_CR24","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/ajcn\/88.1.224","volume":"88","author":"TP Ng","year":"2008","unstructured":"Ng, T. P., Feng, L., Niti, M., Kua, E. H. & Yap, K. B. Tea consumption and cognitive impairment and decline in older Chinese adults. Am J Clin Nutr \n                           88, 224\u201331 (2008).","journal-title":"Am J Clin Nutr"},{"key":"12156_CR25","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1016\/j.neuroscience.2009.07.014","volume":"163","author":"Q Li","year":"2009","unstructured":"Li, Q. et al. Long-term green tea catechin administration prevents spatial learning and memory impairment in senescence-accelerated mouse prone-8 mice by decreasing Abeta1-42 oligomers and upregulating synaptic plasticity-related proteins in the hippocampus. Neuroscience \n                           163, 741\u20139 (2009).","journal-title":"Neuroscience"},{"key":"12156_CR26","doi-asserted-by":"publisher","first-page":"1631S","DOI":"10.3945\/ajcn.113.058263","volume":"98","author":"J van Duynhoven","year":"2013","unstructured":"van Duynhoven, J. et al. Interactions of black tea polyphenols with human gut microbiota: implications for gut and cardiovascular health. Am J Clin Nutr \n                           98, 1631S\u20131641S (2013).","journal-title":"Am J Clin Nutr"},{"key":"12156_CR27","doi-asserted-by":"publisher","first-page":"239","DOI":"10.3945\/jn.114.206508","volume":"145","author":"P Wang","year":"2015","unstructured":"Wang, P. et al. Oat avenanthramide-C (2c) is biotransformed by mice and the human microbiota into bioactive metabolites. J Nutr \n                           145, 239\u201345 (2015).","journal-title":"J Nutr"},{"key":"12156_CR28","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s00394-015-0852-y","volume":"54","author":"A Duda-Chodak","year":"2015","unstructured":"Duda-Chodak, A., Tarko, T., Satora, P. & Sroka, P. Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review. Eur J Nutr \n                           54, 325\u201341 (2015).","journal-title":"Eur J Nutr"},{"key":"12156_CR29","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.1053\/j.gastro.2009.08.042","volume":"137","author":"MA Hildebrandt","year":"2009","unstructured":"Hildebrandt, M. A. et al. High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology \n                           137, 1716\u201324 (2009).","journal-title":"Gastroenterology"},{"key":"12156_CR30","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.mam.2012.11.001","volume":"34","author":"J Shen","year":"2013","unstructured":"Shen, J., Obin, M. S. & Zhao, L. The gut microbiota, obesity and insulin resistance. Mol Aspects Med \n                           34, 39\u201358 (2013).","journal-title":"Mol Aspects Med"},{"key":"12156_CR31","doi-asserted-by":"publisher","first-page":"1761","DOI":"10.2337\/db06-1491","volume":"56","author":"PD Cani","year":"2007","unstructured":"Cani, P. D. et al. Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes \n                           56, 1761\u201372 (2007).","journal-title":"Diabetes"},{"key":"12156_CR32","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.4049\/jimmunol.176.5.3070","volume":"176","author":"MD Neal","year":"2006","unstructured":"Neal, M. D. et al. Enterocyte TLR4 mediates phagocytosis and translocation of bacteria across the intestinal barrier. J Immunol \n                           176, 3070\u20139 (2006).","journal-title":"J Immunol"},{"key":"12156_CR33","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.nutres.2015.12.001","volume":"36","author":"SM Lim","year":"2016","unstructured":"Lim, S. M., Jeong, J. J., Woo, K. H., Han, M. J. & Kim, D. H. Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression. Nutr Res \n                           36, 337\u201348 (2016).","journal-title":"Nutr Res"},{"key":"12156_CR34","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152922","volume":"11","author":"V Karuppagounder","year":"2016","unstructured":"Karuppagounder, V. et al. Modulation of Macrophage Polarization and HMGB1-TLR2\/TLR4 Cascade Plays a Crucial Role for Cardiac Remodeling in Senescence-Accelerated Prone Mice. PLoS One \n                           11, e0152922 (2016).","journal-title":"PLoS One"},{"key":"12156_CR35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0147897","volume":"11","author":"DK Singla","year":"2016","unstructured":"Singla, D. K., Singla, R. & Wang, J. BMP-7 Treatment Increases M2 Macrophage Differentiation and Reduces Inflammation and Plaque Formation in Apo E\u2212\/\u2212 Mice. PLoS One \n                           11, e0147897 (2016).","journal-title":"PLoS One"},{"key":"12156_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/srep21618","volume":"6","author":"H Lin","year":"2016","unstructured":"Lin, H., An, Y., Hao, F., Wang, Y. & Tang, H. Correlations of Fecal Metabonomic and Microbiomic Changes Induced by High-fat Diet in the Pre-Obesity State. Sci Rep \n                           6, 21618 (2016).","journal-title":"Sci Rep"},{"key":"12156_CR37","doi-asserted-by":"publisher","first-page":"2374","DOI":"10.1007\/s00125-007-0791-0","volume":"50","author":"PD Cani","year":"2007","unstructured":"Cani, P. D. et al. Selective increases of bifidobacteria in gut microflora improve high-fat-diet-induced diabetes in mice through a mechanism associated with endotoxaemia. Diabetologia \n                           50, 2374\u201383 (2007).","journal-title":"Diabetologia"},{"key":"12156_CR38","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1017\/S0007114512001213","volume":"108","author":"AP Moreira","year":"2012","unstructured":"Moreira, A. P. et al. Influence of a high-fat diet on gut microbiota, intestinal permeability and metabolic endotoxaemia. Br J Nutr \n                           108, 801\u20139 (2012).","journal-title":"Br J Nutr"},{"key":"12156_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007125","volume":"4","author":"F Armougom","year":"2009","unstructured":"Armougom, F., Henry, M., Vialettes, B., Raccah, D. & Raoult, D. Monitoring bacterial community of human gut microbiota reveals an increase in Lactobacillus in obese patients and Methanogens in anorexic patients. PLoS One \n                           4, e7125 (2009).","journal-title":"PLoS One"},{"key":"12156_CR40","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1038\/ijo.2013.20","volume":"37","author":"M Million","year":"2013","unstructured":"Million, M. et al. Correlation between body mass index and gut concentrations of Lactobacillus reuteri, Bifidobacterium animalis, Methanobrevibacter smithii and Escherichia coli. Int J Obes (Lond) \n                           37, 1460\u20136 (2013).","journal-title":"Int J Obes (Lond)"},{"key":"12156_CR41","doi-asserted-by":"publisher","first-page":"1470","DOI":"10.2337\/db07-1403","volume":"57","author":"PD Cani","year":"2008","unstructured":"Cani, P. D. et al. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice. Diabetes \n                           57, 1470\u201381 (2008).","journal-title":"Diabetes"},{"key":"12156_CR42","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1159\/000248992","volume":"55","author":"PG Steenhout","year":"2009","unstructured":"Steenhout, P. G., Rochat, F. & Hager, C. The effect of Bifidobacterium lactis on the growth of infants: a pooled analysis of randomized controlled studies. Ann Nutr Metab \n                           55, 334\u201340 (2009).","journal-title":"Ann Nutr Metab"},{"key":"12156_CR43","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.micpath.2012.05.007","volume":"53","author":"M Million","year":"2012","unstructured":"Million, M. et al. Comparative meta-analysis of the effect of Lactobacillus species on weight gain in humans and animals. Microb Pathog \n                           53, 100\u20138 (2012).","journal-title":"Microb Pathog"},{"key":"12156_CR44","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1631\/jzus.2005.B0787","volume":"6","author":"WL Hu","year":"2005","unstructured":"Hu, W. L., Wu, Y. M., Liu, J. X., Guo, Y. Q. & Ye, J. A. Tea saponins affect in vitro fermentation and methanogenesis in faunated and defaunated rumen fluid. J Zhejiang Univ Sci B \n                           6, 787\u201392 (2005).","journal-title":"J Zhejiang Univ Sci B"},{"key":"12156_CR45","doi-asserted-by":"publisher","DOI":"10.1186\/1754-6834-6-161","volume":"6","author":"Y Feng","year":"2013","unstructured":"Feng, Y. et al. Effects of tea saponin on glucan conversion and bonding behaviour of cellulolytic enzymes during enzymatic hydrolysis of corncob residue with high lignin content. Biotechnol Biofuels \n                           6, 161 (2013).","journal-title":"Biotechnol Biofuels"},{"key":"12156_CR46","doi-asserted-by":"crossref","DOI":"10.1590\/1414-431X20154543","volume":"49","author":"T Fang","year":"2016","unstructured":"Fang, T. et al. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats. Braz J Med Biol Res \n                           49, e5287 (2016).","journal-title":"Braz J Med Biol Res"},{"key":"12156_CR47","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.spen.2014.10.001","volume":"21","author":"A Legido","year":"2014","unstructured":"Legido, A. & Katsetos, C. D. Experimental studies in epilepsy: immunologic and inflammatory mechanisms. Semin Pediatr Neurol \n                           21, 197\u2013206 (2014).","journal-title":"Semin Pediatr Neurol"},{"key":"12156_CR48","doi-asserted-by":"publisher","first-page":"188","DOI":"10.1016\/j.bbi.2016.10.012","volume":"60","author":"C Balducci","year":"2017","unstructured":"Balducci, C. et al. Toll-like receptor 4-dependent glial cell activation mediates the impairment in memory establishment induced by \u03b2-amyloid oligomers in an acute mouse model of Alzheimer\u2019s disease. Brain Behav Immun \n                           60, 188\u2013197 (2017).","journal-title":"Brain Behav Immun"},{"key":"12156_CR49","doi-asserted-by":"publisher","first-page":"13798","DOI":"10.1073\/pnas.0702553104","volume":"104","author":"SC Tang","year":"2007","unstructured":"Tang, S. C. et al. Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci USA \n                           104, 13798\u2013803 (2007).","journal-title":"Proc Natl Acad Sci USA"},{"key":"12156_CR50","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1038\/ncb1629","volume":"9","author":"A Rolls","year":"2007","unstructured":"Rolls, A. et al. Toll-like receptors modulate adult hippocampal neurogenesis. Nat Cell Biol \n                           9, 1081\u20138 (2007).","journal-title":"Nat Cell Biol"},{"key":"12156_CR51","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.bbi.2016.04.004","volume":"56","author":"T Chen","year":"2016","unstructured":"Chen, T. et al. Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice. Brain Behav Immun \n                           56, 42\u201355 (2016).","journal-title":"Brain Behav Immun"},{"key":"12156_CR52","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.brainres.2011.04.014","volume":"1396","author":"GZ Li","year":"2011","unstructured":"Li, G. Z. et al. Expression of myeloid differentiation primary response protein 88 (Myd88) in the cerebral cortex after experimental traumatic brain injury in rats. Brain Res \n                           1396, 96\u2013104 (2011).","journal-title":"Brain Res"},{"key":"12156_CR53","doi-asserted-by":"publisher","first-page":"7471","DOI":"10.4049\/jimmunol.0900762","volume":"183","author":"X Wang","year":"2009","unstructured":"Wang, X. et al. Lipopolysaccharide sensitizes neonatal hypoxic-ischemic brain injury in a MyD88-dependent manner. J Immunol \n                           183, 7471\u20137 (2009).","journal-title":"J Immunol"},{"key":"12156_CR54","doi-asserted-by":"publisher","first-page":"364","DOI":"10.1254\/jphs.14025FP","volume":"125","author":"L Tao","year":"2014","unstructured":"Tao, L. et al. 1-O-tigloyl-1-O-deacetyl-nimbolinin B inhibits LPS-stimulated inflammatory responses by suppressing NF-\u03baB and JNK activation in microglia cells. J Pharmacol Sci \n                           125, 364\u201374 (2014).","journal-title":"J Pharmacol Sci"},{"key":"12156_CR55","doi-asserted-by":"publisher","first-page":"721","DOI":"10.2174\/1570159X14666160119094646","volume":"14","author":"JC Zhang","year":"2016","unstructured":"Zhang, J. C., Yao, W. & Hashimoto, K. Brain-derived Neurotrophic Factor (BDNF)-TrkB Signaling in Inflammation-related Depression and Potential Therapeutic Targets. Curr Neuropharmacol \n                           14, 721\u201331 (2016).","journal-title":"Curr Neuropharmacol"},{"key":"12156_CR56","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1111\/1440-1681.12538","volume":"43","author":"M Motaghinejad","year":"2016","unstructured":"Motaghinejad, M., Motevalian, M. & Shabab, B. Neuroprotective effects of various doses of topiramate against methylphenidate induced oxidative stress and inflammation in rat isolated hippocampus. Clin Exp Pharmacol Physiol \n                           43, 360\u201371 (2016).","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"Pt A","key":"12156_CR57","first-page":"100","volume":"113","author":"SJ Jeon","year":"2016","unstructured":"Jeon, S. J. et al. Oleanolic acid ameliorates cognitive dysfunction caused by cholinergic blockade via TrkB-dependent BDNF signaling. Neuropharmacology \n                           113(Pt A), 100\u2013109 (2016).","journal-title":"Neuropharmacology"},{"key":"12156_CR58","unstructured":"Carlson, A. L. et al. Variation in the infant gut microbiome is associated with cognitive development and brain morphometry. In Annual Meeting of the American College of Neuropsychoparmacology. ACNP (2016)."},{"key":"12156_CR59","doi-asserted-by":"publisher","first-page":"15625","DOI":"10.1073\/pnas.1005807107","volume":"107","author":"E Okun","year":"2010","unstructured":"Okun, E. et al. Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis. Proc Natl Acad Sci USA \n                           107, 15625\u201330 (2010).","journal-title":"Proc Natl Acad Sci USA"},{"key":"12156_CR60","doi-asserted-by":"publisher","first-page":"1459","DOI":"10.1038\/sj.ijo.0801747","volume":"25","author":"LK Han","year":"2001","unstructured":"Han, L. K. et al. Anti-obesity effects in rodents of dietary teasaponin, a lipase inhibitor. Int J Obes Relat Metab Disord \n                           25, 1459\u201364 (2001).","journal-title":"Int J Obes Relat Metab Disord"},{"key":"12156_CR61","doi-asserted-by":"publisher","first-page":"3130","DOI":"10.1210\/en.2013-1218","volume":"154","author":"Y Yu","year":"2013","unstructured":"Yu, Y. et al. Teasaponin reduces inflammation and central leptin resistance in diet-induced obese male mice. Endocrinology \n                           154, 3130\u201340 (2013).","journal-title":"Endocrinology"},{"key":"12156_CR62","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1369\/0022155416631803","volume":"64","author":"CH Dinh","year":"2016","unstructured":"Dinh, C. H. et al. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice. J Histochem Cytochem \n                           64, 237\u201355 (2016).","journal-title":"J Histochem Cytochem"},{"key":"12156_CR63","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002575","volume":"3","author":"G Arqu\u00e9","year":"2008","unstructured":"Arqu\u00e9, G. et al. Impaired spatial learning strategies and novel object recognition in mice haploinsufficient for the dual specificity tyrosine-regulated kinase-1A (Dyrk1A). PLoS One \n                           3, e2575 (2008).","journal-title":"PLoS One"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12156-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12156-2","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12156-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T11:25:57Z","timestamp":1671794757000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-12156-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,9,22]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["12156"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-12156-2","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,9,22]]},"assertion":[{"value":"20 April 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 August 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"12203"}}