Prevention of HIV coat protein (gp120) toxicity in cortical cell cultures by riluzole.
Neurological complications observed in HIV-infected patients are very frequent. Neocortical lesions include reduced neuronal density due to neuronal degeneration. The HIV envelope protein gp120 has potent neurotoxic properties in cell cultures blocked either by NMDA antagonists or calcium channel antagonists. Moreover, human monocytoid cell lines infected by HIV release endogenous toxic factors with comparable cellular actions. We have analysed the effects of riluzole, a compound reducing the excitatory amino acid release on gp120-induced neurotoxicity in primary neuronal cultures. Riluzole, which blocks the release of glutamate and aspartate from nerve terminals, prevents (10(-7) M) the neuronal degeneration produced by 20 pM of gp120 in cortical cell cultures. This result could suggest that toxic factors produced by activated macrophages might increase glutamate release, and that this may be prevented by riluzole.
Unité de Neurobiologie Cellulaire, Faculté de Médecine, Limoges, France.
P
P
Sindou
P
P
Couratier
F
F
Esclaire
C
C
Yardin
A
A
Bousseau
J
J
Hugon
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists; D015699:HIV Envelope Protein gp120 / Q000633:toxicity*; D015497:HIV-1 / Q000378:metabolism; D009410:Nerve Degeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D051381:Rats; D019782:Riluzole; D013844:Thiazoles / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D018696:Neuroprotective Agents; D010446:Peptide Fragments; D013844:Thiazoles; D019782:Riluzole