QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Davies, B. Articles by Lathe, R. Search for Related Content PubMed PubMed Citation Articles by Davies, B. Articles by Lathe, R.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 15, 2001, 21(18):6993-7000

Loss of Hippocampal Serine Protease BSP1/Neuropsin Predisposes to Global Seizure Activity

Ben Davies¹, Ian R. Kearns², Jan Ure¹, Ceri H. Davies², and Richard Lathe¹

¹ Center for Genome Research and ² Department of Neuroscience, Center for Neuroscience, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom

Serine proteases in the adult CNS contribute both to activity-dependent structural changes accompanying learning and to the regulation of excitotoxic cell death. Brain serine protease 1 (BSP1)/neuropsin is a trypsin-like serine protease exclusively expressed, within the CNS, in the hippocampus and associated limbic structures. To explore the role of this enzyme, we have used gene targeting to disrupt this gene in mice. Mutant mice were viable and overtly normal; they displayed normal hippocampal long-term synaptic potentiation (LTP) and exhibited no deficits in spatial navigation (water maze). Nevertheless, electrophysiological studies revealed that the hippocampus of mice lacking this specifically expressed protease possessed an increased susceptibility for hyperexcitability (polyspiking) in response to repetitive afferent stimulation. Furthermore, seizure activity on kainic acid administration was markedly increased in mutant mice and was accompanied by heightened immediate early gene (c-fos) expression throughout the brain. In view of the regional selectivity of BSP1/neuropsin brain expression, the observed phenotype may selectively reflect limbic function, further implicating the hippocampus and amygdala in controlling cortical activation. Within the hippocampus, our data suggest that BSP1/neuropsin, unlike other serine proteases, has little effect on physiological synaptic remodeling and instead plays a role in limiting neuronal hyperexcitability induced by epileptogenic insult.

Key words: brain serine protease; BSP1; cortex; epileptiform; fos; hippocampus; kainic acid; knock-out; long-term potentiation; LTP; mouse; mutant; neuropsin; seizure; targeting

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21186993-08$05.00/0

This article has been cited by other articles:

				F. L. Scott, J. Sun, J. C. Whisstock, K. Kato, and P. I. Bird SerpinB6 is an Inhibitor of Kallikrein-8 in Keratinocytes J. Biochem., October 1, 2007; 142(4): 435 - 442. [Abstract] [Full Text] [PDF]

				T. Bushell The emergence of proteinase-activated receptor-2 as a novel target for the treatment of inflammation-related CNS disorders J. Physiol., May 15, 2007; 581(1): 7 - 16. [Abstract] [Full Text] [PDF]

				H. Li, H. Chen, L. Bao, K. F. Manly, E. J. Chesler, L. Lu, J. Wang, M. Zhou, R. W. Williams, and Y. Cui Integrative genetic analysis of transcription modules: towards filling the gap between genetic loci and inherited traits Hum. Mol. Genet., February 1, 2006; 15(3): 481 - 492. [Abstract] [Full Text] [PDF]

				H. Tamura, Y. Ishikawa, N. Hino, M. Maeda, S. Yoshida, S. Kaku, and S. Shiosaka Neuropsin is essential for early processes of memory acquisition and Schaffer collateral long-term potentiation in adult mouse hippocampus in vivo J. Physiol., February 1, 2006; 570(3): 541 - 551. [Abstract] [Full Text] [PDF]

				Y. Li, Y.-p. Qian, X.-j. Yu, Y.-q. Wang, D.-g. Dong, W. Sun, R.-m. Ma, and B. Su Recent Origin of a Hominoid-Specific Splice Form of Neuropsin, a Gene Involved in Learning and Memory Mol. Biol. Evol., November 1, 2004; 21(11): 2111 - 2115. [Abstract] [Full Text] [PDF]

				M. A. LYNCH Long-Term Potentiation and Memory Physiol Rev, January 1, 2004; 84(1): 87 - 136. [Abstract] [Full Text] [PDF]

				F. Molinari, V. Meskanaite, A. Munnich, P. Sonderegger, and L. Colleaux Extracellular proteases and their inhibitors ingenetic diseases of the central nervous system Hum. Mol. Genet., October 15, 2003; 12(90002): R195 - 200. [Abstract] [Full Text] [PDF]

				K. Matsumoto-Miyai, A. Ninomiya, H. Yamasaki, H. Tamura, Y. Nakamura, and S. Shiosaka NMDA-Dependent Proteolysis of Presynaptic Adhesion Molecule L1 in the Hippocampus by Neuropsin J. Neurosci., August 27, 2003; 23(21): 7727 - 7736. [Abstract] [Full Text] [PDF]

				I. A. Scarisbrick, S. I. Blaber, C. F. Lucchinetti, C. P. Genain, M. Blaber, and M. Rodriguez Activity of a newly identified serine protease in CNS demyelination Brain, June 1, 2002; 125(6): 1283 - 1296. [Abstract] [Full Text] [PDF]

				T. Oka, T. Hakoshima, M. Itakura, S. Yamamori, M. Takahashi, Y. Hashimoto, S. Shiosaka, and K. Kato Role of Loop Structures of Neuropsin in the Activity of Serine Protease and Regulated Secretion J. Biol. Chem., April 19, 2002; 277(17): 14724 - 14730. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help