Retrograde transport of transmissible mink encephalopathy within descending motor tracts

Jason C. Bartz, Anthony Kincaid, Richard A. Bessen

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

The spread of the abnormal conformation of the prion protein, PrPSc, within the spinal cord is central to the pathogenesis of transmissible prion diseases, but the mechanism of transport has not been determined. For this report, the route of transport of the HY strain of transmissible mink encephalopathy (TME), a prion disease of mink, in the central nervous system following unilateral inoculation into the sciatic nerves of Syrian hamsters was investigated. PrPSc was detected at 3 weeks postinfection in the lumbar spinal cord and ascended to the brain at a rate of approximately 3.3 mm per day. At 6 weeks postinfection, PrPSc was detected in the lateral vestibular nucleus and the interposed nucleus of the cerebellum ipsilateral to the site of sciatic nerve inoculation and in the red nucleus contralateral to HY TME inoculation. At 9 weeks postinfection, PrPSc was detected in the contralateral hind limb motor cortex and reticular thalamic nucleus. These patterns of PrPSc brain deposition at various times postinfection were consistent with that of HY TME spread from the sciatic nerve to the lumbar spinal cord followed by transsynaptic spread and retrograde transport to the brain and brain stem along descending spinal tracts (i.e., lateral vestibulospinal, rubrospinal, and corticospinal). The absence of PrPSc from the spleen suggested that the lymphoreticular system does not play a role in neuroinvasion following sciatic nerve infection. The rapid disease onset following sciatic nerve infection demonstratec that HY TME can spread by retrograde transport along specific descending motor pathways of the spinal cord and, as a result, can initially target brain regions that control vestibular and motor functions. The early clinical symptoms of HY TME infection such as head tremor and ataxia were consistent with neuronal damage to these brain areas.

Original languageEnglish
Pages (from-to)5759-5768
Number of pages10
JournalJournal of Virology
Volume76
Issue number11
DOIs
StatePublished - 2002

Fingerprint

transmissible mink encephalopathy
PrPSc proteins
Mink
Brain Diseases
Sciatic Nerve
Spinal Cord
nerve tissue
spinal cord
brain
Brain
Prion Diseases
prion diseases
Infection
Lateral Vestibular Nucleus
infection
Red Nucleus
Efferent Pathways
Thalamic Nuclei
mink
prions

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Retrograde transport of transmissible mink encephalopathy within descending motor tracts. / Bartz, Jason C.; Kincaid, Anthony; Bessen, Richard A.

In: Journal of Virology, Vol. 76, No. 11, 2002, p. 5759-5768.

Research output: Contribution to journalArticle

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