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Neuropsin regulates an early phase of Schaffer-collateral long-term potentiation in the murine hippocampus

Authors


: Dr S. Shiosaka, as above.
E-mail: sshiosak@bs.aist-nara.ac.jp

Abstract

We found that neuropsin, an extracellular matrix serine protease, has a regulatory effect on Schaffer-collateral long-term potentiation (LTP) in the mouse hippocampus. Bath application of 1–170 n m recombinant neuropsin modulated early phase LTP in the Schaffer-collateral pathway with a ‘bell-shape’ dose–response curve. The maximum enhancing activity (134% of control LTP) was found at ∼ 2.5 nm. Bath application of a neutralizing antibody against neuropsin in the hippocampal slice resulted in a marked inhibition of the tetanus-induced early phase of LTP. The in vivo continuous intraventricular infusion of an antisense oligonucleotide against neuropsin significantly reduced the amplitude of the tetanus-induced early phase of LTP in vitro. Neuropsin did not directly change the N-methyl d-aspartate (NMDA) current. Thus, neuropsin appears to act as a regulatory molecule in the early phase of LTP via its proteolytic function on extracellular matrix rather than affecting NMDA receptor-mediated calcium increase.

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