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Aging Neurosci."],"abstract":"<jats:p>Aquaporin-4 (AQP4) is highly polarized to perivascular astrocytic endfeet. Loss of AQP4 polarization is associated with many diseases. In Alzheimer\u2019s disease (AD), AQP4 loses its normal location and thus reduces the clearance of amyloid-\u03b2 plaques and tau protein. Clinical and experimental studies showed that moxibustion can improve the learning and memory abilities of AD. To explore whether moxibustion can affect the polarization of AQP4 around the blood-brain barrier (BBB), we used spatial transcriptomics (ST) to analyze the expression and polarization of <jats:italic>Aqp4<\/jats:italic> in wild-type mice, APP\/PS1 mice, and APP\/PS1 mice intervened by moxibustion. The results showed that moxibustion improved the loss of abnormal polarization of AQP4 in APP\/PS1 mice, especially in the hypothalamic BBB. Besides, the other 31 genes with <jats:italic>Aqp4<\/jats:italic> as the core have similar depolarization in APP\/PS1 mice, most of which are also membrane proteins. The majority of them have been reversed by moxibustion. At the same time, we employed the cerebrospinal fluid circulation gene set, which was found to be at a higher level in the group of APP\/PS1 mice with moxibustion treatment. Finally, to further explore its mechanism, we analyzed the mitochondrial respiratory chain complex enzymes closely related to energy metabolism and found that moxibustion can significantly increase the expression of mitochondrial respiratory chain enzymes such as Cox6a2 in the hypothalamus, which could provide energy for mRNA transport. Our research shows that increasing the polarization of hypothalamic <jats:italic>Aqp4<\/jats:italic> through mitochondrial energy supply may be an important target for moxibustion to improve cognitive impairment in APP\/PS1 mice.<\/jats:p>","DOI":"10.3389\/fnagi.2023.1069155","type":"journal-article","created":{"date-parts":[[2023,2,2]],"date-time":"2023-02-02T05:21:47Z","timestamp":1675315307000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Moxibustion improves hypothalamus Aqp4 polarization in APP\/PS1 mice: Evidence from spatial transcriptomics"],"prefix":"10.3389","volume":"15","author":[{"given":"Shuqing","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongying","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weikang","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junmeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenyu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lushuang","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaofeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1367","DOI":"10.1016\/j.drudis.2016.05.020","article-title":"In vitro blood-brain barrier models for drug research: state-of-the-art and new perspectives on reconstituting these models on artificial basement membrane platforms.","volume":"21","author":"Banerjee","year":"2016","journal-title":"Drug Discov. 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