Figure 2.

Prions spread along defined neuroanatomical pathways. (A) Prions inoculated through the intraperitoneal route (i.p.) initially accumulate in the spleen (1) before spreading along autonomic nerves into the thoracic spinal cord (2). Subsequent spread is rostrally within the spinal cord (3) to the brainstem and eventually into the brain (4). (B) Intragastric prion inoculation results in PrP^Sc accumulation in the myenteric plexus of the enteric nervous system (ENS) then subsequent spread along sympathetic efferent nerves to the thoracic spinal cord or directly to the dorsal motor nucleus of the vagus (DMNV) via parasympathetic vagal efferents. As with i.p. routes, spread occurs rostrally within the spinal cord to the brain. (C) Intraneural infection of prions results in spread along defined neuroanatomical pathways. In the case of the sciatic nerve, prion spread occurs along nerve roots to the VMNs of the lumbar spinal cord (1). Subsequent spread of prions in the spinal cord occurs in the rostral direction (2 and 3) toward brainstem nuclei that include the red nucleus (RN), vestibular nucleus, and cortex (4 and 5). Image created with BioRender.com, accessed on 28 February 2022.