Acute intermittent hypoxia (AIH) elicits phrenic long-term facilitation (pLTF), a form of respiratory neuroplasticity characterized by a persistent increase in phrenic neural drive. A key mechanistic component facilitating AIH-induced pLTF is the neurotrophin brain-derived neurotrophic factor (BDNF), which signals through its high-affinity tropomyosin receptor kinase B (TrkB) in phrenic motor neurons (PhMNs). Spinal BDNF expression and subsequent TrkB activation are necessary for AIH-induced pLTF. Studies from our laboratory indicate that circulating steroid hormones are also required to permit AIH-induced pLTF in both females and males. For example, AIH-induced pLTF is eliminated in orchiectomized (male gonadectomy; ORX) male rats expressing low levels of circulating testosterone, the primary male sex hormone. Prior published studies suggest that ORX is associated with reduced BDNF expression in other parts of the central nervous system. The relationship between circulating testosterone and BDNF/TrkB expression in the spinal cord, especially in regions associated with expression of AIH-induced pLTF, has not been characterized. We hypothesized that loss of testosterone in ORX male rats would alter the expression of BDNF and TrkB in PhMNs, providing a potential mechanism to explain loss of AIH-induced pLTF following ORX. To test our hypothesis, young adult male Sprague Dawley rats underwent ORX or sham surgery. Rats were euthanized at either 7 or 14 days post surgery and cervical spinal tissue was processed for analysis. Western blot (WB; 7 and 14 day rats; ventral cervical spinal cord tissue) and immunohistochemical (IHC; 14 day rats; C3-C6 ventral horn tissue) analyses were performed to quantify spinal BDNF and TrkB protein expression. Our WB data indicate that ORX minimally impacted the expression of BDNF or TrkB protein in the cervical ventral horn relative to sham rats at 7 and 14 days. These findings are supported by preliminary IHC data indicating that BDNF is similar between ORX and sham rats at 14 days in the phrenic motor nucleus. Based on our findings, BDNF/TrkB expression does not appear to be disrupted following ORX in male rats, disproving our hypothesis. This research was supported by NIH NHLBI R01HL146477 and the University of Minnesota Division of Physical Therapy and Rehabilitation Science. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Davis et al. (Fri,) studied this question.