4-Hydroxynonenal modulates the long-term potentiation induced by L-type Ca2+ channel activation in the rat dentate gyrus in vitro.
Increased oxyradical production and membrane lipid peroxidation (MLP) occur under physiological and degenerative conditions in neurons. We investigated whether 4-hydroxynonenal (4HN), one of the membrane lipid peroxidation products, affects long-term potentiation (LTP) in the rat dentate gyrus in vitro. Treatment of hippocampal slices with 4HN (10 microM) enhanced LTP without affecting basal evoked potentials. The enhancement was completely inhibited by 2 microM nifedipine, a blocker of L-type Ca2+ channels. In cultured dentate gyrus neurons, treatment of the cells with 4HN for 24 h resulted in a significant amount of cell death that was detoxified by glutathione, whereas short-term treatment with 4HN (< or = 6 h) had no effect. Nifedipine partially but significantly suppressed the 4HN-induced cell death. These results suggest that 4HN modulates LTP and induces delayed cell death through L-type Ca2+ channel activation in the dentate gyrus. 4HN thereby plays an important role in both physiological and pathophysiological events in the hippocampus.
Department of Pharmacology, College of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
Tatsuhiro
T
Akaishi
Ken
K
Nakazawa
Kaoru
K
Sato
Yasuo
Y
Ohno
Yoshihisa
Y
Ito
D000447:Aldehydes / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects*; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D005071:Evoked Potentials / Q000187:drug effects; D005978:Glutathione; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats
D000447:Aldehydes; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015853:Cysteine Proteinase Inhibitors; D005978:Glutathione; D009543:Nifedipine; C027576:4-hydroxy-2-nonenal