Macrophage Migration Inhibitory Factor (MIF) Acts in the Paraventricular Nucleus of the Hypothalamus (PVN) to Decrease the Corticosterone Response to Stress

Abstract

MIF acts within PVN neurons to attenuate the excitatory actions of the neuropeptide angiotensin II, but is absent in PVN neurons of Spontaneously Hypertensive rats (SHR). Since angiotensin II in the PVN activates the hypothalamic pituitary adrenal axis resulting in corticosterone (Cort) secretion from the adrenal, we tested the hypothesis that restoration of MIF within SHR PVN neurons will attenuate the Cort response to stress. AAV2‐based viral vectors were microinjected into the PVN to express either GFP (n=6) or MIF (n=7) in adult male 11 week old SHR. Three weeks later a femoral arterial catheter was implanted under isoflurane anesthesia. At least 3 days later, rats were subjected to 60 min of restraint stress. Prior to stress, baseline plasma Cort was not significantly different between GFP‐ and MIF‐treated rats (6±1 and 4±1 μg/dl). However, during stress, plasma Cort was significantly (P<0.05) lower in MIF‐ compared with GFP‐treated rats at 15 min (36±2 vs 43±2 μg/dl) and 45 min (48±3 vs 58±2 μg/dl), and tended to be lower (P=0.057) at 60 min (48±2 vs 59±5 μg/dl). Thus, the integrated average increase in Cort during stress was significantly lower in MIF‐ compared with GFP‐treated rats (39±2 vs 44±1 μg/dl/min). We conclude that MIF acts in the PVN to attenuate the Cort response to restraint stress. Supported by HL093186 (MPI Sumners and Scheuer)