Soluble cerebrospinal fluid factors induce Ca2+ dysregulation in rat cultured cortical astrocytes in HIV-1-associated dementia complex.
OBJECTIVE
To investigate the effect of cerebrospinal fluid (CSF) of HIV-1-seropositive patients with and without HIV-1-associated dementia complex (HADC) on the intracellular Ca2+ regulation of cultured cortical astrocytes.


METHODS
In a blinded study the effects of CSF samples from HADC patients and from HIV-1-seropositive but not demented patients on intracellular Ca2+ regulation of cultured cortical astrocytes were investigated. Astrocytes were chosen because they contribute to both electrophysiological and immunological processes within the brain.


METHODS
Astrocytes were incubated in CSF samples for 1 h, loaded with the Ca2+ indicator dye Fura-2 and intracellular Ca2+ responses upon glutamate application were measured.


RESULTS
CSF samples from 10 out of 11 HADC patients induced a significant reduction of the intracellular Ca2+ increase upon glutamate application. On the contrary, seven out of 10 CSF samples from HIV-1-seropositive patients without HADC as well as 10 out of 10 CSF samples from HIV-1-seronegative controls did not affect the intracellular Ca2+ response.


CONCLUSIONS
Our data strongly confirm the hypothesis that CSF samples of HADC patients contain soluble factors which interfere with the function of astrocytes. These factors may include HIV-1 proteins, locally released cytokines or neurotoxins.
Köller
H
H
Department of Neurology and the aInstitute of Medical Microbiology and Virology, Heinrich-Heine-University, Düsseldorf, Germany.
von Giesen
H J
HJ
Schaal
H
H
Arendt
G
G
D015526:AIDS Dementia Complex / Q000134:cerebrospinal fluid* / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015415:Biomarkers / Q000737:chemistry; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility
D015415:Biomarkers; D018698:Glutamic Acid; D002118:Calcium