Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase.
Approximately 35% of HIV-infected subjects, both children and adults, exhibit alterations in the sleep-waking cycle. HIV surface glycoprotein gp120 has been postulated to contribute to this abnormality. For example, it has been reported that HIVgp120 modifies sleep in freely-moving rats and that it also activates the ERK pathway in brain slices. The goal of this work was to determine if sleep changes induced by HIVgp120 in normal rats are mediated by the MAPK pathway. Our results show that a single intraventricular administration of HIVgp120 selectively increases REMS and that such an increase can be prevented by U0126, an inhibitor of ERK activating enzyme, MEK. In contrast, SB202190, a MAPK-p38 inhibitor, had no effect on HIVgp120-induced increase in REMS. These results suggest that HIVgp120 increases REMS in the rat by specifically affecting the ERK signal transduction pathway.
Díaz-Ruiz
O
O
Grupo de Neurociencias, Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México, Apartado postal 70-250, 04510 México D.F., Mexico.
Navarro
L
L
Méndez-Díaz
M
M
Galicia
O
O
Elder
J H
JH
Sanna
P P
PP
Drucker-Colín
R
R
Prospéro-García
O
O
D015526:AIDS Dementia Complex / Q000201:enzymology* / Q000503:physiopathology / Q000821:virology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000821:virology; D002070:Butadienes / Q000494:pharmacology; D004347:Drug Interactions / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015699:HIV Envelope Protein gp120 / Q000378:metabolism / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D020923:REM Sleep Parasomnias / Q000139:chemically induced / Q000201:enzymology* / Q000821:virology; D051381:Rats; D017208:Rats, Wistar; D012895:Sleep, REM / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases
D002070:Butadienes; D004791:Enzyme Inhibitors; D015699:HIV Envelope Protein gp120; D007093:Imidazoles; D009570:Nitriles; D011725:Pyridines; C113580:U 0126; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole