PMID- 11704882
OWN - NLM
STAT- MEDLINE
DCOM- 20020204
LR  - 20181113
IS  - 1355-0284 (Print)
IS  - 1355-0284 (Linking)
VI  - 7
IP  - 6
DP  - 2001 Dec
TI  - Activation of microglia cells is dispensable for the induction of rat retroviral 
      spongiform encephalopathy.
PG  - 501-10
AB  - In the course of retroviral CNS infections, microglia activation has been 
      observed frequently, and it has been hypothesized that activated microglia 
      produce and secrete neurotoxic products like proinflammatory cytokines, by this 
      promoting brain damage. We challenged this hypothesis in a rat model for 
      neurodegeneration. In a kinetic study, we found that microglia cells of rats 
      neonatally inoculated with neurovirulent murine leukemia virus (MuLV) NT40 became 
      infected in vivo to maximal levels within 9-13 days postinoculation (d.p.i.). 
      Beginning from 13 d.p.i., degenerative alterations, i.e., vacuolization of 
      neurons and neuropil were found in cerebellar and other brain-stem nuclei. 
      Elevated numbers of activated microglia cells--as revealed by immunohistochemical 
      staining with monoclonal antibody ED1--were first detected at 19 d.p.i. and were 
      always locally associated with degenerated areas but not with nonaltered, yet 
      infected, brain regions. Both neuropathological changes and activated microglia 
      cells increased in intensity and numbers, respectively, with ongoing infection 
      but did not spread to other than initially affected brain regions. By 
      ribonuclease protection assays, we were unable to detect differences in the 
      expression levels of tumor-necrosis-factor-alpha (TNF-alpha), interleukin-1beta 
      (IL-1beta), and interleukin-6 (IL-6) in microglia cells nor in total brains from 
      infected versus uninfected rats. Our results suggest that the activation of 
      microglia in the course of MuLV neurodegeneration is rather a reaction to, and 
      not the cause of, neuronal damage. Furthermore, overt expression of the 
      proinflammatory cytokines TNF-alpha, IL-1beta, and IL-6 within the CNS is not 
      required for the induction of retroviral associated neurodegeneration in rats.
FAU - Hansen, R
AU  - Hansen R
AD  - Institut fur Virologie und Immunbiologie, Universitat Wurzburg, Germany.
FAU - Sauder, C
AU  - Sauder C
FAU - Czub, S
AU  - Czub S
FAU - Bachmann, E
AU  - Bachmann E
FAU - Schimmer, S
AU  - Schimmer S
FAU - Hegyi, A
AU  - Hegyi A
FAU - Czub, M
AU  - Czub M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurovirol
JT  - Journal of neurovirology
JID - 9508123
RN  - 0 (Interleukin-1)
RN  - 0 (Interleukin-6)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Envelope Proteins)
SB  - IM
MH  - Animals
MH  - Cerebral Cortex/immunology
MH  - Encephalitis, Viral/immunology/pathology/virology
MH  - Gene Expression/immunology
MH  - Immunohistochemistry
MH  - Interleukin-1/genetics/immunology
MH  - Interleukin-6/genetics/immunology
MH  - *Leukemia Virus, Murine
MH  - Microglia/*immunology/virology
MH  - Neurodegenerative Diseases/*immunology/pathology/*virology
MH  - RNA, Messenger/analysis
MH  - Rats
MH  - Rats, Inbred F344
MH  - Retroviridae Infections/*immunology/pathology
MH  - Tumor Necrosis Factor-alpha/genetics/immunology
MH  - Viral Envelope Proteins/analysis/immunology
EDAT- 2001/11/13 10:00
MHDA- 2002/02/05 10:01
CRDT- 2001/11/13 10:00
PHST- 2001/11/13 10:00 [pubmed]
PHST- 2002/02/05 10:01 [medline]
PHST- 2001/11/13 10:00 [entrez]
AID - 10.1080/135502801753248088 [doi]
PST - ppublish
SO  - J Neurovirol. 2001 Dec;7(6):501-10. doi: 10.1080/135502801753248088.