Lithium ameliorates HIV-gp120-mediated neurotoxicity.
To investigate the protective effects of lithium against HIV-gp120-mediated toxicity in vivo, mice were exposed to lithium and gp120 and levels of the neuronal markers, microtubule-associated protein-2 and NeuN, and the astrocyte marker, glial fibrillary acidic protein, were determined. In addition, SH-SY5Y neuronal cells exposed to gp120 and lithium were assessed for cell viability. Lithium pretreatment protected the hippocampus of mice from gp120-mediated toxicity. Similarly, preexposure of neuronal cultures to lithium significantly reduced gp120-associated neurotoxicity. However, posttreatment with lithium had minimal neuroprotective effects against gp120, both in vivo and in vitro. The protective effects of lithium in vitro were blocked by LY294002, an inhibitor of the phosphatidylinositol 3-kinase/Akt pathway. Taken together, these results demonstrate that lithium might be neuroprotective against gp120-mediated toxicity and suggest that prophylactic treatment with lithium may prevent the onset/progression of HIV-associated cognitive impairments.
Everall
Ian P
IP
Section of Experimental Neuropathology and Psychiatry, Institute of Psychiatry, London, United Kingdom.
Bell
Christopher
C
Mallory
Margaret
M
Langford
Dianne
D
Adame
Anthony
A
Rockestein
Edward
E
Masliah
Eliezer
E
D015526:AIDS Dementia Complex / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000473:pathology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D015699:HIV Envelope Protein gp120 / Q000187:drug effects* / Q000633:toxicity; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology / Q000821:virology; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy / Q000821:virology; D009474:Neurons / Q000187:drug effects* / Q000821:virology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009498:Neurotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D017966:Pyramidal Cells / Q000187:drug effects / Q000473:pathology; D016896:Treatment Outcome
D015699:HIV Envelope Protein gp120; D018696:Neuroprotective Agents; D009498:Neurotoxins; D008094:Lithium; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3