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The synchronous and reciprocal regulation of the activities of cysteine proteases associated with long-term plasticity

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Abstract

Using hippocampal slices from Wistar rats, we studied the correlation between modifications of the activities of cysteine proteases in various models of long-term plasticity. CA3-CA1 long-term depression (LTD) was induced according to the standard procedure by low-frequency stimulation (1 Hz, 900 impulses). Long-term potentiation (LTP) was induced by high-frequency stimulation (HFS) of Schaffer collaterals (100 Hz, 1 s) and followed by a 1-h recording. After the end of the experiments, the slices were immediately frozen at −70°C and the activities of caspase-3 and calpain were measured in each slice separately. We hypothesized that increased intracellular calcium content associated with long-term plasticity may be accompanied by synchronous regulation of these proteases. Complex study of the proteolytic activities of caspase-3 and calpain supported our hypothesis that long-term plasticity is accompanied by changes in their balance; however, these changes were specific for each type of plasticity. We did not find any correlation between caspase-3 and calpain activities in the passive control slices, which were not electrically stimulated. However, the activities of these enzymes correlated after stimulation of Schaffer collaterals using all protocols of the induction of long-term plasticity. We observed a positive correlation between the activities of caspase-3 and calpain after the induction of LTD or depotentiation. This effect was probably due to caspase-dependent proteolysis of calpastatin, a natural inhibitor of calpain. In contrast, in slices with LTP maintenance for 1 h after HFS, this correlation was inversed. This fact poorly conforms to the initial hypothesis. Possible mechanisms that underlie the inversion of the ratio of activation of cysteine proteases are discussed.

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Correspondence to I. V. Kudryashova.

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Original Russian Text © I.V. Kudryashova, M.V. Onufriev, 2013, published in Neirokhimiya, 2013, Vol. 30, No. 1, pp. 29–34.

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Kudryashova, I.V., Onufriev, M.V. The synchronous and reciprocal regulation of the activities of cysteine proteases associated with long-term plasticity. Neurochem. J. 7, 23–28 (2013). https://doi.org/10.1134/S1819712413010054

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