Activation of Corticotropin Releasing Factor Receptors in the Rostral Ventrolateral Medulla is Required for Glucose-Induced Sympathoexcitation

Megan E. Bardgett, Amanda L. Sharpe, Glenn M. Toney.Am J Physiol Endocrinol Metab (September 30, 2014). doi:10.1152/ajpendo.00291.2014.

Glucose leads to increased energy expenditure  through activation sympathetic nerve activity (SNA). The mechanism that leads to the activation of SNA is unknown. PVN and RVLM play an important role in the control of SNA and BP.  We already know that PVN not directly projects down to the IML in order to control SNA and BP but there is a direct projection to RVLM from PVN. Also neurons in the PVN are activated by glucose. The activity of RVLM is controlled mainly by Glutamate and GABA but we also know that there are other neurotransmitters that may be involved such as corticotropin releasing factor (CRF). So it has been shown that there are CRFergic neuron in the PVN. The hypothesis for the study in this article was that glucose leads to increases in SNA through activation of CRFergic neurons in the PVN that ultimately lead to activation of RVLM neuron by activating CRF receptor that lead to sympathoexcitation.  In order to prove this they provided anatomical along with function data. The data provided showed that glucose infusion elevates both LSNA and SSNA. They also demonstrated that glucose does, in fact, activate neurons in both RVLM and PVN. Not only that but the majority of PVN neurons that expressed c-fos was also a CRFergic neuron. As for RVLM, they showed that glucose activated a significant portion of TH RVLM neurons. Blockade of CRF receptor blunted the increases in LSNA and SSNA in response to glucose infusion. They also showed that kyn blocks the increase in SNA in response to glucose. Final they demonstrated that blockade of PVN blocked the response to glucose infusion. These data demonstrate that glucose leads to activation of SNA by activating CRFergic neurons in the PVN and this leads to the release of CRF and this leads to activation or the CRF receptor and this may facilitate the release of glutamate in the RVLM and this leads to increases in SNA and thus energy expenditure. I wonder how SNA in our model might behave in response to glucose infusion…-MD