Anatomical differences between male and female axons in the brain could make women more vulnerable to experience a concussion than men, according to researchers from the University of Pennsylvania.
Women have smaller, more breakable nerve fibers in the brain compared to men, the researchers note, in a study published recently in the journal Experimental Neurology,
These smaller axons had fewer microtubules—“train tracks” that transport molecules up and down the axons—that were more likely to break after applying the same amount of force from a simulated traumatic brain injury. That breaking is what the researchers believe may lead to symptoms associated with concussions, such as dizziness or loss of consciousness, explains a media release from University of Pennsylvania School of Medicine.
“There is a fundamental, anatomical difference between male and female axons,” says Douglas H. Smith, MD, director of the Penn Center for Brain Injury and Repair and the Robert A. Groff Professor of Neurosurgery at the Perelman School of Medicine at the University of Pennsylvania, leader of the research team.
“In the male axon, there are a great number of microtubules, which make the entire structure stronger, whereas in female axons, it’s more of a leaner type of architecture, so it’s not as strong.”
Considered the “electric grid” of the brain, axons are long, slender parts of the neuron that communicate messages from one cell to another. When someone suffers a traumatic blow to the head, the axons are stretched at a very rapid rate. While the axons typically stay intact, their microtubules can break under the strain. The faster they stretch, the stiffer the crosslinking proteins known as tau become. This transfers high stress onto the microtubule that can result in them rupturing, setting off a molecular imbalance.
This buildup causes abnormal inflows of sodium and calcium ions. Researchers believe that levels of calcium become high enough to trigger a self-destruct process, in which protein-breaking enzymes are unleashed, begin to degrade the axonal structure, and ultimately compromise the nerve fiber.
The researchers found that 24 hours after trauma, female axons had significantly more swellings and a greater loss of calcium signaling function than male axons, the release continues.
“When axons function normally, they let sodium pass through the membrane, and it creates a spark that can be transferred as ‘electricity’ down the axon,” Smith states. “In concussion, you can have immediate loss of that ability to transfer that ‘electricity.’ That’s why the characteristic, behavioral changes occur.”
The research team used transmission electron microscopy to study the structural differences between female and male axons from both rat and human neurons. Next, they evaluated the axons’ response to dynamic stretch injury, to mimic a traumatic axonal injury, using computational and in vitro models.
The in vitro findings, researchers share in the release, may have implications for concussion, where axonal injury is the most commonly described pathological feature. “It is conceivable that under the same level of mechanical loading during head impact, axons in female brains may be more susceptible to damage than axons in male brains due to fundamental differences in axon ultrastructure,” they write.
Further research is needed to support these findings, Smith adds, noting that their findings are pointing them to potential treatment options to study.
[Source(s): University of Pennsylvania School of Medicine, Science Daily]