ROSTROCAUDAL‐DEPENDENT DECREASES IN BRAIN‐DERIVED NEUROTROPHIC FACTOR IN THE ROSTRAL VENTROLATERAL MEDULLA OF SEDENTARY VERSUS PHYSICALLY ACTIVE RATS

Abstract

The rostral ventrolateral medulla (RVLM) contains bulbospinal neurons that contribute to normal and pathologically‐related increases in sympathetic nerve activity. Both structural and functional forms of neuroplasticity occur in the RVLM following sedentary versus physical active conditions, and are subregion specific. For example, in the rostral subregion of the RVLM, sedentary rats exhibit greater sympathoexcitation in response to glutamate microinjections (functional neuroplasticity) as well as more extensive dendritic branching (structural neuroplasticity), both consistent with increased excitability. Although these findings suggest a link between subregion‐specific neuroplasticity in the RVLM and inactivity‐related cardiovascular diseases, the mechanisms mediating these alterations remain unknown. The role of brain‐derived neurotrophic factor (BDNF) is well established in the field of neuroplasticity in terms of neuronal growth and remodeling. It has also been proposed that BDNF serves as a neurotransmitter in brainstem regions involved in sympathetic outflow. Whether sedentary conditions alter levels of the mature form of BDNF (mBDNF, which promotes dendritic branching) or the pro‐form of BDNF (proBDNF, which inhibits dendritic branching) in the RVLM is unknown. The purpose of this study was to test the hypothesis that mBDNF is increased and proBDNF is decreased in more rostral regions of the RVLM, particularly in sedentary rats. To test this hypothesis, male Sprague‐Dawley rats were divided into two groups: physically active (running wheels) and sedentary (without wheels, n=6 ea). Animals were housed for 10–12 weeks before sacrificing for fresh tissue removal. Frozen brainstems were cryosectioned at 80 μm, from which bilateral tissue punches were obtained for Western blotting. Punches were pooled based on their location relative to the caudal pole of the facial nucleus (FN+480; FN+240; FN‐240; FN‐480 μm), as determined in cresyl violet‐stained, post‐punched sections. The RVLMs of sedentary and active rats exhibited rostrocaudal‐dependent levels of mBDNF, with rostral regions exhibiting significant increases compared to caudal regions (main effect; p=0.039). However, sedentary rats exhibited significantly less mBDNF at FN+240 to FN‐480 (p<0.05 vs active). proBDNF levels were also lower in sedentary rats (p<0.05) as were TrkB receptors, the primary receptor for mBDNF (p<0.001; full length‐TrkB; p=0.002; truncated‐TrkB), suggesting an overall decrease in mBDNF signaling in sedentary rats. These results further demonstrate activity‐dependent neuroplasticity in subregions of the RVLM, but do not support a contribution of mBDNF towards the increased dendritic branching in rostral regions of the RVLM following sedentary conditions. In contrast, reductions in the pro‐form of BDNF and loss of its inhibitory effect on dendritic branching may contribute to increased dendritic branching in sedentary animals. Future studies could also examine BDNF‐induced alterations in synaptic transmission as well as other neurotrophic growth factors, all of which may contribute to increased cardiovascular disease in sedentary individuals via influences on sympathetic outflow.Support or Funding InformationHL096787‐07; AHA25810010This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.