Investigating Expression of Serotonin and Neurokinin-1 Receptors as a Cause of Respiratory Failure in Mice

• Matthew Douglass, Neuroscience, University of Delaware

• Cameron Grover, Department of Biological Sciences, Delaware State University

Spinal muscular atrophy (SMA) is a neurodegenerative disease that affects up to 1 in 10,000 live births. If left untreated in humans, patients often die of respiratory failure by age 2 due to the degeneration of the neurons that control breathing. In this study, we examined a region of the brainstem known as the pre-Bötzinger complex (pre-BötC) to discern the exact cellular path that is the origin of that respiratory failure. Serotonin and a neuropeptide known as Substance P, both released by specialized neurons in the Nucleus Raphe Obscurus, act through specific receptors to modulate breathing frequency. Some evidence even suggests that without these substances, respiration would not occur at all. Using a technique known as immunohistochemistry in a common mouse model of SMA, we fluorescently labeled serotonin (5-HT_2A) and Substance P (NK1) receptors for comparison between healthy and sick mice. We expect that mice with SMA will have fewer of the receptor proteins that respond to these substances, resulting in the cessation of breathing that we see in SMA patients. By elucidating the exact mechanism behind this disease’s lethality, we may be able to produce new treatment options to more effectively maintain patients’ longevity and quality of life.