Muskoxen (Ovibos moschatus) and bighorn sheep (Ovis canadensis) are known for their dramatic head-to-head battles. But all that noggin-knocking has a cost, researchers from the Icahn School of Medicine at Mount Sinai in New York City say: much like people who hit their head too often, the animals exhibit signs of brain damage, including an increase in phosphorylated tau protein.
“It seems like animals like muskoxen and bighorn sheep get traumatic brain injuries,” says Icahn evolutionary biologist Nicole Ackermans, who spearheaded the study published May 17 in Acta Neuropathologica. However, outside experts tell The Scientist that more research is needed to determine whether the findings truly indicate brain damage from headbutting.
Searching for the telltale signs of traumatic brain injuries
Studies have found that athletes of sports such as soccer, football, and rugby who sustain blows to the head run the risk of developing brain injuries, especially when hits are repeated over time. Such injuries have also been linked to neurodegenerative diseases such as Alzheimer’s. The trouble is, traditional animal models have notable differences in brain biology and physiology that limit their utility for understanding traumatic brain injuries (TBI). “There’s no perfect model right now,” says Ackermans.
The hunt for a better study system is what drew Ackermans to muskoxen and sheep—species that repeatedly sustain intense blows to their heads throughout their lives. “We thought if we wanted to find out if [animals] get traumatic brain injury or not, bighorn sheep would be the ones to look at,” she says.
Immunostaining for phosphorylated tau (brown) in muskox brain slices revealed abnormal clumps of axons and other pathologies associated with traumatic brain injuries in humans.
Courtesy of Nicole Ackermans
To determine if the animals sustain TBIs similar to humans, the researchers examined their brains for established indicators of human TBIs. The researchers used a technique known as immunohistochemistry to analyze thin slices of brain tissue from naturally deceased muskoken (three individuals), bighorn sheep (four individuals), a person who died with late-stage Alzheimer’s disease, and a person who died with chronic traumatic encephalopathy (CTE). With this method, the team highlighted phosphorylated tau—a version of the protein that increases in prevalence with age and is associated with neurodegenerative diseases—and looked for the clumps of microglia that characterize neurodegenerative diseases. “Once we had this data, we did some counting and looked at different patterns across the brain,” says Ackermans, comparing the animal brains with the human ones.
While the microglial clumps seen in human samples were rare in the animals’ brains, other similarities were present. Specifically, in the muskoxen samples, the authors noted the presence of axon clusters packed with phosphorylated tau, which were especially prevalent on the outer edges of the cerebral cortex—a distribution pattern “reminiscent of mild TBI or early-stage CTE cases,” the authors write. They also detected approximately eight times the number of these clusters in the oldest muskox brain than in a middle-aged one (both were female animals, which would be expected to engage in less headbutting than males). Less pathology was evident in the sheep brains, which the authors suggest could be because the animals were captive and younger, limiting their headbutting experience. Still, the team notes “a human specimen with the same tau pathology present in the male bighorn sheep would have likely been diagnosed with mild CTE.”
The researchers’ brain slices from bighorn sheep didn’t exhibit much pathology, but they were mostly from young captive animals, which may not have engaged in head-to-head battles as much as older wild individuals.
Bovids as brain injury models?
Taken together, Ackermans tells The Scientist that the findings suggest that these animals could help researchers to understand brain injury progression and treatment in humans.
“I think their hypothesis makes sense,” says Stellenbosch University neuroscientist Tando Maduna, who was not involved in the study. But while she says the research has the potential to inform the scientific understanding of TBIs in humans, the small number of samples is a “big limitation” of the study. “You cannot compare a female aged animal to a male that is involved in ramming and then with a female human that has Alzheimer’s,” she says, adding that “there is still room to investigate other parameters and precise indicators, but so far what I see here is more of an indication of aging and neurodegeneration.”
Neuroanatomist Vivien Shaw of Hull York Medical School in the UK says the authors did a good job with the study but they “overstated their conclusion.” The report failed to prove that the tau protein patterns seen in the animals’ brains resulted from headbutting, she says. “They tried to say that because people with repetitive brain injury have tau proteins and the muskoxen and the bighorn sheep have some [tau proteins], that it’s all the same thing, but they didn’t show that,” says Shaw. Especially since the samples were from older animals, “they haven’t shown if it’s just normal aging or if it’s caused by headbutting,” she adds, and therefore, saying muskoxen and bighorn sheep can be used as a model for investigating what happens in the human brain is a “big stretch.”
Ackermans acknowledges that the team’s sample size was limited—the species studied are hard to obtain samples from, she says—but counters the notion that the data they provided aren’t conclusive. “The samples were enough to at least indicate the presence or absence of this pathology,” she says, adding that the tau pattern is a “definite indication that [TBI from chronic trauma] at least exists in a certain form” in these animals.