INTERMITTENT INDUCED CHANGES IN GENE EXPRESSION IN THE MEDIAN PREOPTIC NUCLEUS (MNPO) OF RATS

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2013-04-12

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Saini, Niharika

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Purpose: Our previous work indicated that changes in MnPO gene expression are necessary for the sustained increase in blood pressure produced by chronic intermittent hypoxia (CIH), an animal model of the hypoxemia associated with sleep apnea. This study tested the effects of a 7d CIH exposure on the expression of additional genes in the MnPO that could contribute to changes in the excitability of neurons in this region: Angiotensin receptor 1a (AT1a), Angiotensin receptor 1b (At1b), delta FBJ murine osteosarcoma viral oncogene homolog B (ΔFosB), transient receptor potential channel 4 (TRPC4), potassium-chloride cotransporter 2 (KCC2), and sodium-potassium-chloride cotransporter 1 (NKCC1). Methods: The brain was harvested from adult male rats anesthetized with inactin (100 mg/kg ip) after 7 d of CIH or 7 d of normoxia. Laser Capture Microdissection of MnPO was carried out from 10µ sections. MnPO samples were run through RNA purification, cDNA synthesis and PCR using S18 as the housekeeping gene. Results: PCR results revealed significant increases in the expression of TRPC4, ΔFosB, NKCC1 and AT1a in the MnPO of CIH treated rats relative to normoxic controls. KCC2 and AT1b gene expression in MnPO were not significantly affected by CIH. Conclusions: The results suggest that increased expression of TRPC4, ΔFosB, NKCC1 and especially AT1a could participate in the contribution of MnPO to the sustained hypertensive effects of CIH.

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