Although earlier studies have reported that Bovine spongiform encephalopathy (BSE, or "mad cow disease") only affects the autonomic nervous system (ANS) after the central nervous system (CNS) has been infected, a new study now reveals that the ANS can show signs of infection prior to involvement of the CNS.
BSE is a fatal neurodegenerative disease in cattle caused by the generation of a misfolded form of protein known as a prion, rather than by a bacterium or virus. Signs of the disease, which can be transmitted to humans, usually show up around 60 months after infection.
The study is published online in The American Journal of Pathology.
Lead researcher of the study, Martin H. Groschup, Ph.D., from the Institute for Novel and Emerging Infectious Diseases at the Friedrich-Loeffler-Institut, Riems, Germany, explained:
"Our results clearly indicate that both pathways are involved in the early pathogenesis of BSE, but not necessarily simultaneously."
In order to gain new insight into the pathogenesis of the disease, the researchers orally infected 56 calves with BSE from infected cattle and 18 calves with BSE-negative material from calf brainstem to serve as controls. The calves were aged between 4-6 months. In addition, the team examined tissue samples from a calf that had died naturally of the disease.
16 months after the calves were infected, the team took tissue samples from the gut, the CNS, and ANS every 4 months until 44 months.
The tissue samples were examined for the presence of prions by immunohistochemistry and were also used to infect mice that are extremely susceptible to a BSE infection.
BSE prions found in the autonomic nervous systemAccording to the researchers, they observed a distinct accumulation of the prion protein in almost all the samples they collected. 16 months after infection, the team found the BSE prions in the sympathetic ANS system; and 20 months after infection they found the prions in the parasympathetic ANS.
In these samples they found little or no sign of infection in the CNS. According to the researchers, the sympathetic part of the ANS was more involved in the early pathogenesis than the parasympathetic part of the ANS.
More animals displaying clinical symptoms showed higher degree of signs of infection in the sympathetic nervous system structures compared with the parasympathetic tissue samples. The researchers note that the earliest time BSE prions could be detected in the brainstem was 24 months after the animals had been infected, although an infection detected in the spinal cord of one animal 16 months after infection indicates that an additional pathway to the brain exists.
Dr. Groschup said:
"The clear involvement of the sympathetic nervous system illustrates that it plays an important role in the pathogenesis of BSE in cattle. Nevertheless, our results also support earlier research that postulated an early parasympathetic route for BSE."
According to Dr. Groschup, the study results suggest three possible neuronal routes for the ascension of BSE prions to the brain: sympathetic, parasympathetic, and spinal cord projections. "Our study sheds light on the pathogenesis of BSE in cattle during the early incubation period, with implications for diagnostic strategies and food-safety measures."
What is the autonomic nervous system (ANS)?The autonomic nervous system regulates vital involuntary bodily functions, including the pumping of the heart, the automatic functioning of several muscles, such as those of the intestinal tract, and the glands.
The autonomic nervous system has two divisions:
- The sympathetic nervous system - this speeds up the heart rate, raises blood pressure, and constricts blood vessels
- The parasympathetic nervous system - this slows the heart rate, relaxes the sphincter muscles, increases gland activity, and raises intestinal activity