Motor neuronal loss and neurofilament-ubiquitin alteration in MoMuLV-ts1 encephalopathy.
A temperature-sensitive mutant of Moloney murine leukemia virus (MoMuLV-ts1) induces immunosuppression and spongiform encephalopathy in susceptible newborn mice. The associated neuronal degeneration primarily involves the motor neurons in specific target areas of the central nervous system (CNS). Neuronal loss occurs in the absence of direct viral infection of neurons and is the most dramatic pathological change in the CNS of infected mice. To quantitatively demonstrate neuronal loss, an unbiased morphometric stereological study was undertaken using the optical disector method. Using highly susceptible FVB/N mice, neuronal loss was quantitated in the tissue sections of brain stem from infected and noninfected mice at 20 and 35 days post inoculation (dpi). Results indicated that there was no significant neuronal loss at 20 dpi, but significant (P < 0.05) at 35 dpi. In addition, histology, transmission electron microscopy and immunohistochemistry revealed Lewy body-like inclusions consisting of aggregates of neurofilaments and cellular organelles. Degenerated neurons and glial cells were heavily ubiquitinated. Together, these results suggest that significant neuronal loss occurs at the end of the disease process and that Lewy body-like formation and protein ubiquitination are part of the pathogenic process in ts1-induced encephalopathy.
Stoica
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Department of Veterinary Pathobiology, Texas A & M University, College Station, TX 77843-4467, USA. GStoica@cvm.tamu.edu
Tasca
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SI
Wong
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PK
D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000473:pathology / Q000648:ultrastructure; D002452:Cell Count; D002490:Central Nervous System / Q000473:pathology; D018792:Encephalitis, Viral / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D008979:Moloney murine leukemia virus; D009046:Motor Neurons / Q000473:pathology* / Q000648:ultrastructure; D016900:Neurofilament Proteins / Q000032:analysis*; D009457:Neuroglia / Q000473:pathology / Q000648:ultrastructure; D012192:Retroviridae Infections / Q000473:pathology*; D014412:Tumor Virus Infections / Q000473:pathology*; D014452:Ubiquitins / Q000032:analysis*
D016900:Neurofilament Proteins; D014452:Ubiquitins