Increasing Sensory Neuron Regeneration in the Injured Spinal Cord with Acute Intermittent Hypoxia
Abstract
The spinal cord allows neurons within the brain to communicate with muscles and sensory receptors of the body via a network of connections called axons. The functional recovery of people with spinal cord injuries is limited by the inability of damaged neurons in the spinal cord to regrow their axon and reform connections with other cells. But neurons sending their axons in the periphery of the body - the arms, legs, and internal organs can re-grow their axon. Our laboratory studies the reasons behind this difference using the mouse model system, in the hopes that understanding how peripheral neurons regenerate can help us understand why spinal cord neurons do not. Recently, we showed that low oxygen levels encourage peripheral neurons to regenerate. We discovered that this depends on a factor called hypoxia induced factor 1a (HIF-1a), which is important to stimulate axon regeneration in peripheral neurons. HIF-1a is a mediator of the cellular response to low oxygen levels. When cellular oxygen levels are low, HIF-1a levels increase to protect the cell from the stress related to low oxygen. This gives us the opportunity to use low oxygen as a non-invasive tool to manipulate axon regenerative capacity. We found that mice breathing air with low oxygen concentrations for short, repetitive periods of times (termed acute intermittent hypoxia, or AIH) regrow their peripheral axons better than mice breathing normal air. In this grant proposal, we will test the genetic and epigenetic mechanisms by which this happens. We will also test whether providing a low-oxygen environment can help neurons in the spinal cord to regrow their axon and improve recovery of function. If it works, it will be a relatively safe and non-invasive way to encourage neuronal regrowth and may lead to treatments that will help people recover from spinal cord injuries.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810729
Entities
People
- Valeria Cavalli
Organizations
- United States Army
- Washington University in St. Louis