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As a key area gating BP regulation, how the hypothalamic paraventricular nucleus (PVN) modulates salt\u2011sensitive hypertension remains unclear. Here, we found that Sik1, a member of the AMP-activated protein kinase family, was upregulated in PVN neurons of mice following a high-salt diet (HSD). When Sik1 was ablated,\n                    <jats:italic>Sik1<\/jats:italic>\n                    knockout mice exhibited an increase in BP upon HSD feeding. Furthermore, specific deletion of the\n                    <jats:italic>Sik1<\/jats:italic>\n                    gene in the nervous system by\n                    <jats:italic>Nestin-Cre<\/jats:italic>\n                    (\n                    <jats:italic>Nestin-Cre;Sik1<\/jats:italic>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    ) resulted in elevated BP after high salt intake. Notably, AAV-Cre-mediated selective ablation of Sik1 in the PVN neurons was sufficient to cause BP elevation following an HSD. In combination with western blot and immunofluorescence detection, single-nucleus RNA sequencing combined with KEGG pathway analysis showed that Sik1 is predominantly expressed in arginine vasopressin (AVP)-positive neurons of the PVN, and in the absence of Sik1, the cellular NF-\u03baB pathway in these neurons is downregulated by HSD. In addition, Sik1 deficiency led to microglial activation within the PVN under HSD conditions. These results suggest that Sik1 in AVP-positive neurons of PVN attenuates HSD-induced blood pressure elevation, possibly via modulation by the NF-\u03baB signaling pathway. Our findings uncover a previously unrecognized role of neuronal Sik1 in salt\u2011sensitive hypertension pathophysiology, advancing our understanding of neurogenic blood pressure regulation.\n                  <\/jats:p>","DOI":"10.1007\/s12035-026-05666-6","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T15:26:29Z","timestamp":1768577189000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Neuronal Sik1 in the Hypothalamic Paraventricular Nucleus Decreases Blood pressure Elevation Following a High-Salt Diet"],"prefix":"10.1007","volume":"63","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuya","family":"Qi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongxin","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weifeng","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohe","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,16]]},"reference":[{"issue":"1","key":"5666_CR1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01430-7","volume":"8","author":"J Ma","year":"2023","unstructured":"Ma J, Li Y, Yang X, Liu K, Zhang X, Zuo X, Ye R, Wang Z et al (2023) Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions. 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