Evidence of neuronal degeneration in C57B1/6 mice infected with the LP-BM5 leukemia retrovirus mixture.
Mice infected with LP-BM5 develop a severe immunodeficiency accompanied by learning and memory deficits, gliosis, and neurotransmitter abnormalities. The neurochemical alterations are consistent with elevated excitotoxin levels, suggesting that infected mice may incur neuronal damage. Although the number of neocortical neurons was unchanged in mice 12 wk after LP-BM5 infection, the expression of cytoskeletal proteins declined, particularly in the frontal and parietal cortex as indicated by MAP2, NF-200, and synaptophysin immunoreactivity. In contrast, the number of striatal neurons decreased 19%. The remaining neurons were smaller, with fewer synaptic boutons, and showed decreased synaptophysin and NF-200, immunoreactivity. Immunoblots of cortex and striatum confirmed decreases in MAP2, NF-200 and synaptophysin expression. Finally, although NCAM expression decreased in the striatum, it increased in the cortex. These results indicate that LP-BM5-infected mice sustain significant neuronal damage, which may contribute to their behavioral deficits. Moreover, the increase in cortical NCAM expression suggests active synaptic remodeling to compensate for the persistent excitotoxic environment in these mice, whereas striatal neurons degenerate. These concurrent degenerative and compensatory processes may also occur in the brains of patients with AIDS dementia complex (ADC), who suffer extensive degeneration of the basal ganglia and cerebral cortex.
Kustova
Y
Y
Laboratory of Bio-Organic Chemistry, NIDDK, National Institutes of Health, Bethesda, MD 20892-0008, USA.
Espey
M G
MG
Sung
E G
EG
Morse
D
D
Sei
Y
Y
Basile
A S
AS
D015526:AIDS Dementia Complex / Q000378:metabolism / Q000473:pathology; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D009052:Leukemia Virus, Murine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D012192:Retroviridae Infections / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors
D008869:Microtubule-Associated Proteins; D019006:Neural Cell Adhesion Molecules; D016900:Neurofilament Proteins; C051774:neurofilament protein H