Gretchen Carpenter ’23, Neuroscience, 22F
Image credit: Keller Jo, U.S. Fish and Wildlife Service
In May 2022, Ackermans et al. from the Icahn School of Medicine at Mount Sinai published an intriguing study, directly contradicting the previous commonly held understanding that humans were the only animals to suffer from chronic traumatic encephalopathy (CTE). The findings? Headbutting muskoxen showed signs of CTE.
CTE is a progressive brain deterioration pattern caused by repetitive brain trauma that causes behavioral and mood changes, memory loss, cognitive decline, dementia, and eventually death (McKee et al., 2015). While symptoms and behavioral signs, coupled with a history of head injuries, are sufficient to make probable diagnoses of CTE, the only official method for diagnosis is by examination of brain tissue during an autopsy. Coroners look for the deposition of the abnormal hyperphosphorylated (43 kDa TAR DNA-binding protein) tau protein, the classic hallmark of brain damage. When present, tau proteins are typically found in tangles of neurons, astrocytes, and neurites (projections from neuronal bodies) around blood vessels (McKee et al., 2015).
CTE is thought to be caused by repeated head injuries such as blows to the head and concussions, making it commonly associated with contact sports like football and boxing. However, despite the reasonably similar behavioral headbutting mechanisms and biological neuronal arrangement of the brains between animals and humans, before 2022 it had been widely thought that animals did not experience brain tauopathy. In fact, many of these animals have historically been used as a model to develop human cerebral protection measures, like helmets (Drake et al., 2016). Although field studies had indicated that these animals might exhibit some of the initial behavioral indications of CTE (Smith, 1976), none had shown evidence of tau protein abnormalities within the brain. Thus, the research Ackermans et al. (2022) published was extremely novel.
Ackermans led a team of colleagues in studying the brains of three deceased muskoxen from Greenland and four bighorn sheep from the United States. Both species are known for their frequent head-to-head collisions in everyday life activities like mating and establishing social hierarchy, making them an attractive candidate for brain research. They reported that from a macroscopic perspective and through use of MRI (magnetic resonance imaging), the brains looked healthy and complete. This type of imaging technique utilizes radio waves to create high resolution images of soft tissues; however, they are currently not detailed enough to visualize specific proteins (Mayo Clinic). Thus, it was through slicing muskoxen brains and closer examination under microscopy that the team found the tau protein. To better quantify their findings, they measured the tau-immunoreactive protein in one-third of the sulci (a groove in the folding of the brain the cerebral cortex that is a common location to look for accumulation) by using three p-tau antibodies (anti-pSer202 tau, anti-pSer202/Thr205 tau, and anti-pSer396/Ser404 tau) in a process called immunohistochemistry (IHC). IHC requires fixed biopsy tissue samples to be subject to solutions of two different antibodies. The primary antibody tags the protein of interest, and then after it is washed, the secondary antibody tags the primary antibody so that it may be detected. They found that these three primary antibodies easily stained muskoxen, and mildly stained the bighorn sheep, indicating that both species of headbutting animals are at risk for developing related neuropathology. Furthermore, they found that female animals were at higher risk for CTE, a finding they attribute to the thicker skulls and horns in males (Ackermans et al., 2022).
Ultimately, these results are just the beginning of a field that warrants further study and understanding, so the bovine model may be used as an avenue for better treatments and preventions in humans. Perhaps a future with tau protein quantifications will allow for official CTE diagnosis before death. Alternatively, bovine brains could be used for neurodegenerative research regarding the altered circuitry that tau proteins cause, with hopes of developing better treatments. At the very least, the previously used bovine model for helmets will be reconsidered, and safer brain protection instruments may be adopted.
References
Ackermans, N., Varghese, M., Williams, T., Grimaldi, N., Selmanovic, E., Alipour, A., Balchandani, P., Reidenberg, J., & Hof, P. (2022). Evidence of traumatic brain injury in headbutting bovids. Acta Neuropathologica, 144(1), 5-26. https://doi.org/10.1007/s00401-022-02427-2
Drake, A., Donahue, T., Stansloski, M., Fox, K., Wheatley, B., & Donahue, S. (2016). Horn and horn core trabecular bone of bighorn sheep rams absorbs impact energy and reduces brain cavity accelerations during high impact ramming of the skull. Acta Biomaterialia, 44, 41-50. https://doi.org/10.1016/j.actbio.2016.08.019
Mayo Clinic (n.d.). MRI. https://www.mayoclinic.org/tests-procedures/mri/about/pac-20384768
Mckee, A., Stein, T., Kiernan, P., & Alvarez, V. (2015). The neuropathology of chronic traumatic encephalopathy. Brain Pathology, 25(3), 350-364. https://doi.org/10.1111/bpa.12248
Smith, T. (1976). Reproductive behavior and related social organization of the muskox on Nunivak Island. [Master’s thesis, University of Alaska]. https://scholarworks.alaska.edu/handle/11122/8001