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Animal Models Provide Look at “Sixth Sense” Genetic Markers

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It may not be the version portrayed in the infamous thriller of the same name, but human beings do, in fact, have a sixth sense: proprioception. Our brain relies on proprioception to give and receive the information it needs to help our bodies perform coordinated movements through space. And new research using animal models has allowed a team of researchers to identify and describe particular molecular markers that may be involved in this elusive “sixth sense.” 

Silhouette of woman moving gracefully in front of sunset

Proprioception: The Sixth Sense

Proprioception is the unconscious “sixth sense” that prevents us from falling over in a dark room, or that allows us to lift a cup to our lips without spilling even when our eyes are closed. For those without proprioception, coordinated movements are impossible. 

As Dr. Niccolò Zampieri, head of the Development and Function of Neural Circuits Lab at the Max Delbrück Center in Berlin, explains, the job of proprioception is to “collect information from the muscles and joints about our movements, our posture and our position in space, and then pass that on to our central nervous system.”

Zampieri and a team of researchers have recently published an article identifying and describing the molecular markers of cells that are involved in this unconscious process.

Proprioceptors and Genetic Markers in Animal Models

Proprioceptive sensory neurons (pSN), also known as proprioceptors, are specialized sensory receptors that detect changes in muscle length, tension, and movement and transmit this information to the brain. These neurons are activated by mechanical stimuli, such as muscle stretch or contraction, and they respond by sending the information about the body’s position back to the brain.

But until recently, almost nothing was known about what molecular systems are in place to facilitate the connections between pSN and the central nervous systems to trigger specific muscles’ movements.

Zampieri and his team wanted to explore this connection. In their research, he and his team looked for the molecular markers that differentiate pSN that control abdominal, back, and limb muscles in animal models.

The team used single-cell sequencing to look at the animal models’ pSN genes, and in doing so, found that the pSN cells for each muscle group indeed have their own characteristic genetic markers. 

Some of the genetic connections the research team was able to observe and identify are for ephrins and receptors, proteins that are “involved in guiding nascent nerve fibers to their target during development of the nervous system.” The team found, for example, that mice who are not able to produce ephrin-A5 have an impaired connection between their pSN and hind leg muscles.

More than that, the team was able to observe that these are fixed genes, active even at the embryonic stage. 

Goals for Future Research

The team is hopeful that their findings will lead to a better understanding of how specific muscle sensory networks develop and function. Ultimately, the goal is to support further research and the development of better neuroprostheses for patients who have suffered spinal cord injuries. 

Implications may be even more far-reaching than that. The team’s research may also support ongoing research into the connection between proprioception and a healthy skeletal system. Based on his team’s findings, Zampieri hypothesizes that faulty proprioception may be the cause of skeletal conditions including hip dysplasia and scoliosis. As he concludes, “If we can better understand our sixth sense, it will be possible to develop novel therapies that effectively counteract these and other types of skeletal damage.”

Scantox is a part of Scantox, a GLP/GCP-compliant contract research organization (CRO) delivering the highest grade of Discovery, Regulatory Toxicology and CMC/Analytical services since 1977. Scantox focuses on preclinical studies related to central nervous system (CNS) diseases, rare diseases, and mental disorders. With highly predictive disease models available on site and unparalleled preclinical experience, Scantox can handle most CNS drug development needs for biopharmaceutical companies of all sizes. For more information about Scantox, visit www.scantox.com.