{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:15:02Z","timestamp":1789143302975,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T00:00:00Z","timestamp":1730332800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82001493"],"award-info":[{"award-number":["82001493"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171308"],"award-info":[{"award-number":["82171308"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["2019M653662"],"award-info":[{"award-number":["2019M653662"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["82001493"],"award-info":[{"award-number":["82001493"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["82171308"],"award-info":[{"award-number":["82171308"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M653662"],"award-info":[{"award-number":["2019M653662"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High salt (HS) consumption is an independent risk factor for neurodegenerative diseases such as dementia, stroke, and cerebral small vessel disease related to cognitive decline. Recently, Alzheimer\u2019s disease-like pathology changes have been reported as consequences of a HS diet in wild-type (wt) mice. However, it has not been revealed how HS diets accelerate the progress of Alzheimer\u2019s disease (AD) in APP\/PS1 mice. Here, we fed APP\/PS1 mice a HS diet or normal diet (ND) for six months; the effects of the HS\/ND on wt mice were also observed. The results of our behavior test reveal that the HS diet exacerbates anxiety, \u03b2-amyloid overload, neuron loss, and synapse damage in the hippocampi of APP\/PS1 mice; this was not observed in HS-treated wt mice. RNA sequencing shows that nearly all serpin family members were increased in the hippocampus of HS-treated APP\/PS1 mice. Gene function analysis showed that a HS diet induces neurodegeneration, including axon dysfunction and neuro-ligand-based dysfunction, and regulates serine protein inhibitor activities. The mRNA and protein levels of Serpina3n were dramatically increased. Upregulated Serpina3n may be the key for \u03b2-amyloid aggregation and neuronal loss in the hippocampus of HS-treated APP\/PS1 mice. Serpina3n inhibition attenuated the anxiety and increased the number of neurons in the hippocampal CA1(cornu ammonis) region of APP\/PS1 mice. Our study provides novel insights into the mechanisms by which excessive HS diet deteriorates anxiety in AD mice. Therefore, decreasing daily dietary salt consumption constitutes a pivotal public health intervention for mitigating the progression of neuropathology, especially for old patients and those with neurodegenerative disease.<\/jats:p>","DOI":"10.3390\/ijms252111731","type":"journal-article","created":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T12:31:32Z","timestamp":1730377892000},"page":"11731","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["High-Salt Diet Accelerates Neuron Loss and Anxiety in APP\/PS1 Mice Through Serpina3n"],"prefix":"10.3390","volume":"25","author":[{"given":"Kaige","family":"Ma","sequence":"first","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenglin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8973-4067","authenticated-orcid":false,"given":"Hanyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanyuan","family":"An","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ge","family":"Li","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lixue","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Li","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghe","family":"Ren","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-3713-5437","authenticated-orcid":false,"given":"Yudan","family":"Bai","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zichang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengfeng","family":"Ji","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyue","family":"Liu","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinman","family":"Gao","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-101X","authenticated-orcid":false,"given":"Zhichao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Institute of Neuroscience, Translational Medicine Institute, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5161-0210","authenticated-orcid":false,"given":"Xinlin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department\/Institute of Neurobiology, School of Basic Medical Sciences, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"},{"name":"Key Laboratory of Ministry of Education for Environment and Genes Related to Diseases, Xi\u2019an Jiaotong University, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1093\/ije\/dyp139","article-title":"Salt intakes around the world: Implications for public health","volume":"38","author":"Brown","year":"2009","journal-title":"Int. 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