1993 Fiscal Year Final Research Report Summary
Pathogenesis of HIV encephalopathy : Specific binding of gp 120 to glycolipids in brain
| Project/Area Number |
04807034
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Virology
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| Research Institution | TOKYO METROPOLITAN INSTITUTE FOR NEUROSCIENCES |
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Principal Investigator |
KIMURA Junko Tokyo Metropolitan Institute for Neuroscience, 微生物学・免疫学研究部門, 主事研究員 (20142151)
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| Project Period (FY) |
1992 – 1993
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| Keywords | HIV encephalophathy / HIV-1 gp120 / glycolipid / Brain culture / Demyelination / Neuronal death |
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| Research Abstract |
In HIV encephalopathy, diffuse demyelination and neuronal loss have been observed frequently, while the pathogenesis of the damage remains obscure. Althourhg the neurotoxicity of gp120 as a causative factor ahs been reported, it is still not recognized. To clarify the neurotoxicity of gp120, its effects on neural cells were examined in rat primary culture of cerebral cortex.
In immature neural cells, gp120 bound to most of neurons and the addition of gp120 (100nM) caused approximately 50% of neuronal death. The toxicity of gp120 against neurons was confirmed its own effect but not due to the contamination of endotoxin or mycoplasma.
While in mature neural cells, gp120 bound to most of oligodendrocytes (Oligo), a small population of type-2 astrocytes and a few small neurons. The addition of gp120 (50-100nM) did not show any tozicity against neurons, but it resulted in significant inhibition of myelin formation. Gp120 can cause a functional disorder of Oligo, because the number of Oligo was not different but their processes were reduced in length and arborization compared with the control. Production of TNF alpha was not detected in gp120-treated culture.
These results show that gp120 might have at least two separate effects on Oligo and neurons under certain conditions. The effects of HIV-1 gp120 could be an explanation for both neuronal loss and diffuse demyelination in HIV encephalopathy.
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