Direct prion neuroinvasion following inhalation into the nasal cavity
ABSTRACT Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Society for Microbiology
2024-12-01
|
| Series: | mSphere |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/msphere.00863-24 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850249158373408768 |
|---|---|
| author | Anthony E. Kincaid Melissa D. Clouse Shawn M. Magrum Jason C. Bartz |
| author_facet | Anthony E. Kincaid Melissa D. Clouse Shawn M. Magrum Jason C. Bartz |
| author_sort | Anthony E. Kincaid |
| collection | DOAJ |
| description | ABSTRACT Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency, we identified neural structures that uniquely innervate the nasal cavity and neural structures known to mediate neuroinvasion following oral infection and used immunohistochemistry to determine the temporal and spatial accumulation of prions from hamster tissue sections containing cell bodies and axons at 2-week intervals following prion exposure. Prions were identified in the trigeminal ganglion, the spinal trigeminal tract in the brainstem, the intermediolateral cell column of the thoracic spinal cord, and the dorsal motor nucleus of the vagus/solitary nucleus complex months prior to detection of prions in the olfactory bulb or superior cervical ganglion. These results indicate that the trigeminal nerve, but not the olfactory nerve or sympathetic nerves, are involved in neuroinvasion following inhalation of prions into the nasal cavity. The detection of prions in the intermediolateral cell column of the thoracic spinal cord and dorsal motor nucleus of the vagus nerve 14 weeks following inhalation is consistent with inoculum crossing the alimentary wall and infecting the enteric nervous system via this route of infection. Neuroinvasion via the trigeminal nerve, in combination with entry into the central nervous system via autonomic innervation of the enteric nervous system, may contribute to increased efficiency of nasal cavity exposure to prions compared with per os exposure in hamsters.IMPORTANCEInhalation of prions into the nasal cavity is thought to be a route of infection in naturally acquired prion diseases. Experimental studies indicate that inhalation of prions is up to two orders of magnitude more efficient compared with ingestion. The mechanisms underlying this observation are poorly understood. We found a previously unreported direct route of neuroinvasion from the nasal cavity to the nervous system. Importantly, the peripheral ganglia involved may be a useful tissue to sample for prion diagnostics. Overall, identification of a new route of neuroinvasion following prion infection may provide an anatomical basis to explain the increased efficiency of infection following prion inhalation. |
| format | Article |
| id | doaj-art-0b4e7deabe9f4bb39cb58f6678541534 |
| institution | OA Journals |
| issn | 2379-5042 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSphere |
| spelling | doaj-art-0b4e7deabe9f4bb39cb58f66785415342025-08-20T01:58:33ZengAmerican Society for MicrobiologymSphere2379-50422024-12-0191210.1128/msphere.00863-24Direct prion neuroinvasion following inhalation into the nasal cavityAnthony E. Kincaid0Melissa D. Clouse1Shawn M. Magrum2Jason C. Bartz3Department of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USADepartment of Biomedical Sciences, School of Medicine, Creighton University, Omaha, Nebraska, USADepartment of Pharmacy Sciences, School of Pharmacy and Health Professions, Creighton University, Omaha, Nebraska, USADepartment of Medical Microbiology and Immunology, School of Medicine, Creighton University, Omaha, Nebraska, USAABSTRACT Inhalation of prions into the nasal cavity is an efficient route of infection. Following inhalation of infectious prions, animals develop disease with a similar incubation period compared with per os exposure, but with greater efficiency. To identify the reason for this increased efficiency, we identified neural structures that uniquely innervate the nasal cavity and neural structures known to mediate neuroinvasion following oral infection and used immunohistochemistry to determine the temporal and spatial accumulation of prions from hamster tissue sections containing cell bodies and axons at 2-week intervals following prion exposure. Prions were identified in the trigeminal ganglion, the spinal trigeminal tract in the brainstem, the intermediolateral cell column of the thoracic spinal cord, and the dorsal motor nucleus of the vagus/solitary nucleus complex months prior to detection of prions in the olfactory bulb or superior cervical ganglion. These results indicate that the trigeminal nerve, but not the olfactory nerve or sympathetic nerves, are involved in neuroinvasion following inhalation of prions into the nasal cavity. The detection of prions in the intermediolateral cell column of the thoracic spinal cord and dorsal motor nucleus of the vagus nerve 14 weeks following inhalation is consistent with inoculum crossing the alimentary wall and infecting the enteric nervous system via this route of infection. Neuroinvasion via the trigeminal nerve, in combination with entry into the central nervous system via autonomic innervation of the enteric nervous system, may contribute to increased efficiency of nasal cavity exposure to prions compared with per os exposure in hamsters.IMPORTANCEInhalation of prions into the nasal cavity is thought to be a route of infection in naturally acquired prion diseases. Experimental studies indicate that inhalation of prions is up to two orders of magnitude more efficient compared with ingestion. The mechanisms underlying this observation are poorly understood. We found a previously unreported direct route of neuroinvasion from the nasal cavity to the nervous system. Importantly, the peripheral ganglia involved may be a useful tissue to sample for prion diagnostics. Overall, identification of a new route of neuroinvasion following prion infection may provide an anatomical basis to explain the increased efficiency of infection following prion inhalation.https://journals.asm.org/doi/10.1128/msphere.00863-24prion diseaseneuroinvasionprion diagnosticsnasal cavitytrigeminal gangliatrigeminal nerve |
| spellingShingle | Anthony E. Kincaid Melissa D. Clouse Shawn M. Magrum Jason C. Bartz Direct prion neuroinvasion following inhalation into the nasal cavity mSphere prion disease neuroinvasion prion diagnostics nasal cavity trigeminal ganglia trigeminal nerve |
| title | Direct prion neuroinvasion following inhalation into the nasal cavity |
| title_full | Direct prion neuroinvasion following inhalation into the nasal cavity |
| title_fullStr | Direct prion neuroinvasion following inhalation into the nasal cavity |
| title_full_unstemmed | Direct prion neuroinvasion following inhalation into the nasal cavity |
| title_short | Direct prion neuroinvasion following inhalation into the nasal cavity |
| title_sort | direct prion neuroinvasion following inhalation into the nasal cavity |
| topic | prion disease neuroinvasion prion diagnostics nasal cavity trigeminal ganglia trigeminal nerve |
| url | https://journals.asm.org/doi/10.1128/msphere.00863-24 |
| work_keys_str_mv | AT anthonyekincaid directprionneuroinvasionfollowinginhalationintothenasalcavity AT melissadclouse directprionneuroinvasionfollowinginhalationintothenasalcavity AT shawnmmagrum directprionneuroinvasionfollowinginhalationintothenasalcavity AT jasoncbartz directprionneuroinvasionfollowinginhalationintothenasalcavity |