Caspase activity is essential for long-term potentiation.
Slices from rat hippocampus were incubated with the caspase-3 inhibitor N-benzyloxycarbonyl-Asp-Glu-Val-Asp fluoromethylketone (Z-DEVD-FMK) or with the inactive peptide N-benzyloxycarbonyl-Phe-Ala fluoromethylketone (Z-Phe-Ala-FMK) for 30 min. The peptides changed neither input-output curves nor paired-pulse effects at 70-msec interpulse intervals, nor amplitudes of pop spikes in the CA1 region 1.0-6.9 hr after the incubation. Slices taken 1.0-1.4 hr after Z-DEVD-FMK or inactive peptide treatment demonstrated similar long-term potentiation (LTP) curves; however, LTP was suppressed significantly (P<0.001) 1.5-3.4 hr after Z-DEVD-FMK treatment when compared to the corresponding inactive peptide group. LTP magnitude correlated with time after Z-DEVD-FMK (r= -0.74; P<0.02) but did not depend on time after the inactive peptide treatment. After 3.5 hr, LTP was blocked completely. Z-DEVD-FMK did not have a significant effect on presynaptic function. The results are the first evidence that inhibition of caspase-3 significantly decreases or fully blocks LTP in the CA1 region and suggest that caspase-3 is essential for LTP. Candidate caspase-3 substrates that may be cleaved for LTP induction and maintenance are discussed.
Gulyaeva
Natalia V
NV
Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow, Russia. nata_gul@yahoo.com
Kudryashov
Igor E
IE
Kudryashova
Irina V
IV
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002154:Calpain / Q000494:pharmacology; D053148:Caspase 3; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology; D004558:Electric Stimulation; D004792:Enzyme Precursors / Q000378:metabolism / Q000502:physiology; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007659:Ketones / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D013997:Time Factors
D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D004792:Enzyme Precursors; D007659:Ketones; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; C057383:MDL 201053; D002154:Calpain; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases