{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:15:31Z","timestamp":1753892131768,"version":"3.41.2"},"reference-count":78,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T00:00:00Z","timestamp":1728432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>An overactive orexin (OX) system is associated with neurogenic hypertension and an exaggerated chemoreflex in spontaneously hypertensive rats (SHRs). However, the chronology and mechanism of this association is unclear. We hypothesized that increased postnatal neurogenesis of OX neurons in SHRs precedes and contributes to the aberrant increase in mean arterial blood pressure (MAP) and the exaggerated response to hypercapnia during postnatal development. Using immunohistochemical methods and bromodeoxyuridine, we mapped the timeline of orexin neuron neurogenesis and maturation during early postnatal development. We then used whole-body plethysmography with EEG and EMG to map the development of mean arterial pressure (MAP) and state regulation. Finally, we used OX-targeted saporin toxin to determine the effects of eliminating excess OX neurons on the elevated MAP and exaggerated chemoreflex in adult SHRs. We found that both SHRs and Wistar\u2013Kyoto (WKY) rats experienced postnatal increases in OX neurons. However, SHRs experienced a greater increase than WKY rats before P15, which led to significantly more OX neurons in SHRs than age-matched WKY controls by P15\u201316 (3,720 \u00b1 780 vs. 2,406 \u00b1 363, <jats:italic>p<\/jats:italic> = 0.005). We found that neurogenesis, as evidenced by BrdU staining in OX-positive neurons, was the primary contributor to the excess OX neurons in SHRs during early postnatal development. While SHRs develop more OX neurons by P15\u201316, SHRs and normotensive WKY control rats have similar MAP during postnatal development until P25 in wakefulness (81.6 \u00b1 6.6 vs. 67.5 \u00b1 6.8\u00a0mmHg, <jats:italic>p<\/jats:italic> = 0.006) and sleep (79.3 \u00b1 6.1 vs. 66.6 \u00b1 6.5, <jats:italic>p<\/jats:italic> = 0.009), about 10 days after the surge of OX neurons. By selectively eliminating excess (\u223c30%) OX neurons in SHRs, we saw a significantly lowered MAP and hypercapnic ventilatory chemoreflex compared to non\u2013lesioned SHRs at P40. Additionally, we found unique signatures in state indicative of the attention defecit phenotype commonly associated with this model. We suggest that the postnatal increase of OX neurons, primarily attributed to exaggerated postnatal OX neurogenesis, may be necessary for the development of higher MAP and exaggerated chemoreflex in SHRs, and modulation of the overactive OX system may have a potential therapeutic effect during the pre-hypertensive period.<\/jats:p>","DOI":"10.3389\/fphys.2024.1341649","type":"journal-article","created":{"date-parts":[[2024,10,9]],"date-time":"2024-10-09T04:56:21Z","timestamp":1728449781000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exaggerated postnatal surge of orexin neurons and the effects of elimination of excess orexin on blood pressure and exaggerated chemoreflex in spontaneously hypertensive rats"],"prefix":"10.3389","volume":"15","author":[{"given":"Savannah","family":"Lusk","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander M.","family":"Moushey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas","family":"Iwakoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christopher G.","family":"Wilson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aihua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Russell","family":"Ray","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1460-9568.2005.04224.x","article-title":"Hypocretin\/orexin\u2013containing neurons are produced in one sharp peak in the developing ventral diencephalon","volume":"22","author":"Amiot","year":"2005","journal-title":"Eur. 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