MBI Research Snapshot: Drs. Alexandria Marciante and Gordon Mitchell

By Michelle Jaffee

The time of day that an experimental oxygen therapy is given highly influences its efficacy in spurring a form of plasticity in the neural system controlling breathing, according to new rat-model research by neuroscientists in UF’s College of Public Health and Health Professions.

Image of a clock displayed as a day. On one side, we see a depiction of a sleeping human and an active mouse, on the other side, a sleeping mouse and active (running) humans. The spines on all the creatues are highlighted with red dots.
Marciante and collaborators demonstrate that intermittent low oxygen has different effects on breathing in the daily rest versus active phase.

The study, published in the journal Function, is the latest advance by the lab of Gordon Mitchell, Ph.D., which has been examining a form of neural plasticity triggered by “therapeutic acute intermittent hypoxia,” or short repeated bursts of slightly lower oxygen than room air. The lab is refining the technique in both rodent studies and human clinical trials as a potential future therapy to restore respiratory movements and other movements such as walking, grasping and swallowing in people with chronic spinal cord injury and ALS.

In the new study, led by Alexandria Marciante, Ph.D., investigators explored changes in efficacy depending on time of day that therapy is delivered — in the rest/sleep phase versus the physically awake/active phase. To do so, they tracked plasticity in phrenic nerve activity (the nerve that activates the diaphragm) at noon and midnight in anesthetized rats. They also measured oxygen, adenosine and serotonin within the spinal cord and examined mechanisms driving plasticity using spinal-cord drug delivery.

The results indicate there is much greater benefit from oxygen therapy during the rest/sleep phase. This finding represents an important step forward in understanding plasticity in motor systems, Mitchell said. This will provide new guidance for future clinical trials and experiments.

“The implication of this paper is that we are currently treating human subjects at the wrong time of day to optimize plasticity and the functional therapeutic benefits to our subjects,” said Mitchell, MBI deputy director and director of the UF Breathing Research and Therapeutics Center (BREATHE). “Based on these findings, we are discussing ways to flip the playing field by shifting treatments with acute intermittent hypoxia to the nocturnal, rest phase of humans suffering from these debilitating disorders.”

Read the paper in the journal Function.