Neuropsin regulates an early phase of schaffer-collateral long-term potentiation in the murine hippocampus.
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 nM 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 approximately 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.
Komai
S
S
Division of Structural Cell Biology, NAIST, 8916-5 Takayama, Ikoma, Nara, 630-0101 Japan.
Matsuyama
T
T
Matsumoto
K
K
Kato
K
K
Kobayashi
M
M
Imamura
K
K
Yoshida
S
S
Ugawa
S
S
Shiosaka
S
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016375:Antisense Elements (Genetics) / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000737:chemistry; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D066298:In Vitro Techniques; D007610:Kallikreins; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D009500:Neutralization Tests; D018408:Patch-Clamp Techniques; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D011994:Recombinant Proteins / Q000494:pharmacology; D012697:Serine Endopeptidases / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D016375:Antisense Elements (Genetics); D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; C094799:KLK8 protein, human; D007610:Kallikreins; D012697:Serine Endopeptidases; D002118:Calcium