Dominant negative inhibition of ΔFosB in the MnPO blocks increases in arterial pressure and increased expression of FosB/ΔFosB along the autonomic axis in chronic intermittently hypoxic rats

Chronic intermittent hypoxia (CIH), an animal model of hypoxemia in sleep apnea patients, increases sympathetic tone, elevates arterial pressure (AP), and increases FosB/ΔFosB staining in the organum vasculosum of the lamina terminalis (OVLT), subfornical organ, (SFO), median preoptic nucleus (MnPO), paraventricular nucleus (PVN), nucleus of the solitary tract (NTS), and rostral ventrolateral medulla (RVLM). This study tested the hypothesis that FosB/ΔFosB activity in the MnPO contributes to increased AP and activation of sympathetic control regions. Rats (n=5–6) were injected in the MnPO with a dominant negative virus expressing ΔJunD (ΔJD) to inhibit FosB/ΔFosB signaling, control vector (GFP), or not injected (CIH); these three groups were exposed to CIH for 7d in the light phase. A fourth group (CON) was neither injected nor exposed to CIH. MnPO ΔJD blocked the increase in AP during CIH. Further, MnPO ΔJD blocked increases in FosB/ΔFosB staining in the PVN ( CON: 13±1 CIH: 29±3 GFP: 29±2 ΔJD: 12±2 cells/section) and RVLM ( CON: 5±1 CIH: 17±2 GFP: 20±1 ΔJD: 8±2) but not the NTS ( CON: 9±2 CIH: 28±4 GFP: 32±2 ΔJD: : 29±3). These data suggest that FosB/ΔFosB mediated changes in gene expression in the MnPO contribute to the increased AP and activation of the PVN and RVLM associated with CIH. CIH‐induced increases in FosB/ΔFosB along the autonomic axis may also mediate increased sympathetic tone during CIH. PO1 HL‐88052.