Involvement of microglia in cerebrospinal fluid glutamate increase in SIV-infected rhesus monkeys (Macaca mulatta)
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Published on: September 19, 2010
E Koutsilieri1, S Sopper, T Heinemann
1Department of Psychiatry, Clinical Neurochemistry, Julius-Maximilians-University, Würzburg, Germany.
Abstract:
Cerebrospinal fluid (CSF) samples were collected from 24 uninfected and 24 SIV251 MPBMC-infected rhesus monkeys during early infection and from 6 animals in a longitudinal design up to 7 months postinfection to investigate excitatory and inhibitory amino acid neurotransmitter levels. During the early infection period CSF amino acid concentrations of infected animals were not significantly different from those of uninfected animals. However, long-term studies demonstrated that gamma-aminobutyric acid (GABA) concentrations were decreased while glutamate concentrations were increased late in infection compared with the preinfection values of the same animals. Moreover, we showed that the source of increased glutamate in animals with AIDS is, at least partially, microglial cells. Our data support the hypothesis that excitotoxicity is involved in immunodeficiency virus-induced neurological disease and propose microglia as a contributor to excitotoxic damage.
Insights
In simian immunodeficiency virus (SIV)-infected monkeys, cerebrospinal fluid (CSF) showed decreased gamma-aminobutyric acid (GABA) and increased glutamate levels late in infection. Microglia contribute to excitotoxicity in virus-induced neurological disease.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Neurological complications are common in human immunodeficiency virus (HIV) infection.
- The exact mechanisms underlying HIV-associated neurodegeneration remain unclear.
- Excitatory and inhibitory amino acid neurotransmitters play crucial roles in brain function and dysfunction.
Purpose of the Study:
- To investigate changes in excitatory and inhibitory amino acid neurotransmitter levels in cerebrospinal fluid (CSF) during simian immunodeficiency virus (SIV) infection.
- To determine the role of microglial cells in altered neurotransmitter levels associated with SIV-induced neurological disease.
Main Methods:
- Cerebrospinal fluid (CSF) samples were collected from SIV-infected and uninfected rhesus monkeys.
- Amino acid concentrations, including glutamate and gamma-aminobutyric acid (GABA), were measured in CSF.
- Longitudinal sampling allowed for tracking changes over time up to 7 months postinfection.
- The contribution of microglial cells to glutamate levels was investigated.
Main Results:
- Early SIV infection did not significantly alter CSF amino acid concentrations compared to controls.
- Late in infection, CSF concentrations of GABA were decreased, while glutamate concentrations were increased compared to pre-infection levels.
- Microglial cells were identified as a source of increased glutamate in SIV-infected animals.
Conclusions:
- Data support the hypothesis that excitotoxicity contributes to virus-induced neurological disease.
- Microglial cells are implicated as a factor in the excitotoxic damage observed in SIV infection.
- These findings offer insights into the pathogenesis of neuroAIDS.
