期刊
BRAIN RESEARCH
卷 1446, 期 -, 页码 56-70出版社
ELSEVIER
DOI: 10.1016/j.brainres.2012.01.074
关键词
Leptin; Carotid body; Chronic intermittent hypoxia; Obstructive sleep apnea; Fos protein; Chemoreceptor reflex pathway; Petrosal ganglion
资金
- Heart and Stroke Foundation of Ontario [2008-030-04]
Glomus cells within the carotid body are known to respond to hypoxic stimuli. Recently, these cells have been shown to express the long form of the leptin receptor (Ob-Rb). However, whether these glomus cells expressing the Ob-Rb are activated by hypoxic stimuli is not known. Therefore, in this study we investigated whether intermittent hypoxia (IH) or changes in circulating levels of leptin induced phosphorylated signal transducer and activator of transcription 3 (pSTAT3), the immediate early gene c-fos protein, or fos-related antigen-1 protein (Fra-1) within carotid body glomus cells that expressed the Ob-Rb, and within neurons Of the petrosal (PG) and nodose (NG) ganglia. Rats were subjected to IH (120 s normoxia, 80s hypoxia for 8 h) or normoxia (8 h), or intravenous injections of leptin (50 or 200 ng/0.1 mL) or the vehicle saline. Plasma leptin levels were measured in animals exposed to IH and normoxia. Exposure to 8 h of IH increased plasma leptin levels greater than 2-fold compared to normoxic controls. Animals were then perfused with Zamboni's fixative, and the region of the carotid bifurcation containing the carotid body and PG/NG complex was removed, paraffin embedded and sectioned at 6 gm for immunohistochemical processing. Carotid body glomus cells were identified by their expression of tyrosine hydroxylase immunoreactivity. These glomus cells also expressed the OB-Rb and were found to express pSTAT3-, fos-, and Fra-1-like immunoreactivity in response to both IH and systemic leptin injections. IH and leptin injections also increased fos and Fra-1 like expression in the PG, NG and jugular ganglion. Taken together, these data suggest IH alters circulating leptin which in turn activates directly carotid body glomus cells to exert a modulatory effect on the peripheral chemoreceptor reflex. (C) 2012 Elsevier B.V. All rights reserved.
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