Soluble cerebrospinal fluid factors induce Ca2+ dysregulation in rat cultured cortical astrocytes in HIV-1-associated dementia complex

Objectives: 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. Design: In a blinded study the effects of CSF samples from HADC patients an d from HIV-1-seropositive but not demented patients on intracellular Ca2+. regulation of cultured cortical astrocytes were investigated. Astrocytes we re chosen because they contribute to both electrophysiological and immunolo gical 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 a pplication 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 c ontrols did not affect the intracellular Ca2+ response. Conclusions: Our data strongly confirm the hypothesis that CSF samples of H ADC patients contain soluble factors which interfere with the function of a strocytes. These factors may include HIV-1 proteins, locally released cytok ines or neurotoxins. (C) 2001 Lippincott Williams & Wilkins.