Related Experiment Videos
Sustained increases in cerebrospinal fluid quinolinic acid concentrations in rhesus macaques (Macaca mulatta)
M P Heyes1, M Gravell, W T London
1Section on Analytical Biochemistry, NIMH, Bethesda, MD 20892.
Abstract:
Sustained increases in CSF concentrations of the excitotoxin quinolinic acid (QUIN) occur in patients with AIDS and have been implicated in the pathogenesis of the AIDS dementia complex. Macaques in captivity may also develop immunodeficiency syndromes caused by retrovirus infection, including simian retrovirus type-D. In the present study, CSF QUIN concentrations were moderately increased in retrovirus type-D-positive/antibody-negative macaques (163.8 +/- 35.1 nmol/l; P less than 0.0001, n = 21) but not virus-negative/antibody-positive macaques (27.4 +/- 9.4 nmol/l, n = 8) compared to uninfected control macaques (23.0 +/- 1.6 nmol/l; n = 22). CSF QUIN concentrations in virus-positive/antibody-negative macaques tended to remain elevated over a 4-20 month period. Post-mortem studies of 9 virus-positive/antibody-negative macaques and 6 virus-negative/antibody-positive macaques revealed inflammatory responses in the brains of 6 of 9 virus-positive/antibody negative macaques, including lymphocytic infiltrates of the choroid plexus in 3 macaques, glial nodules in 3 macaques and perivascular infiltrates in 1 macaque. These lesions were not extensive and no evidence of brain atrophy was observed. No lesions were observed in the 6 antibody-positive/virus-negative macaques. Small increases in plasma L-kynurenine in virus-positive/antibody-negative macaques are consistent with activation of indoleamine-2,3-dioxygenase, the first enzyme in the kynurenine pathway. We conclude that sustained moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques. The increases in CSF QUIN may reflect inflammatory responses within the brain or synthesis of QUIN precursors in systemic tissues, their entry into brain and subsequent conversion to QUIN. The neuropathologic significance of these increases in CSF QUIN remains to be determined.
Insights
Sustained increases in cerebrospinal fluid (CSF) quinolinic acid (QUIN) were observed in macaques infected with simian retrovirus type-D. These elevations may be linked to brain inflammation, but their neuropathological significance requires further study.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Elevated cerebrospinal fluid (CSF) quinolinic acid (QUIN) is linked to AIDS dementia in humans.
- Simian retrovirus type-D causes immunodeficiency syndromes in macaques.
Purpose of the Study:
- To investigate CSF QUIN concentrations in macaques infected with simian retrovirus type-D.
- To explore potential links between retroviral infection, QUIN levels, and neuropathology in macaques.
Main Methods:
- Measured CSF QUIN concentrations in retrovirus type-D-positive/antibody-negative, virus-negative/antibody-positive, and control macaques.
- Conducted post-mortem brain examinations for inflammatory responses.
- Assessed plasma L-kynurenine levels.
Main Results:
- CSF QUIN was moderately increased in virus-positive/antibody-negative macaques but not in antibody-positive/virus-negative macaques compared to controls.
- Elevated CSF QUIN levels persisted over 4-20 months in infected macaques.
- Brain inflammation, including choroid plexus infiltrates and glial nodules, was observed in some infected macaques, but brain atrophy was absent.
Conclusions:
- Sustained, moderate increases in CSF QUIN occur in viremic simian retrovirus type-D macaques.
- Increased CSF QUIN may result from brain inflammation or peripheral synthesis and subsequent brain entry.
- The neuropathological significance of these QUIN increases in macaques remains undetermined.