PMID- 11549709
DA - 20010910
DCOM- 20011004
IS - 1529-2401
VI - 21
IP - 18
DP - 2001 Sep 15
TI - Loss of hippocampal serine protease BSP1/neuropsin predisposes to global seizure activity.
PG - 6993-7000 AB - 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.
AD - Center for Genome Research and Department of Neuroscience, Center for
Neuroscience, University of Edinburgh, Edinburgh EH9 3JQ, United Kingdom.
FAU - Davies, B
AU - Davies B
FAU - Kearns, I R
AU - Kearns IR
FAU - Ure, J
AU - Ure J
FAU - Davies, C H
AU - Davies CH
FAU - Lathe, R
AU - Lathe R
LA - eng
PT - Journal Article
CY - United States
TA - J Neurosci
JID - 8102140
RN - 0 (Proto-Oncogene Proteins c-fos)
RN - 0 (RNA, Messenger)
RN - 487-79-6 (Kainic Acid)
RN - EC 3.4.21 (Serine Endopeptidases)
RN - EC 3.4.21.- (neuropsin)
SB - IM
MH - Action Potentials
MH - Animal
MH - Behavior, Animal
MH - Cell Line
MH - Electric Stimulation
MH - Excitatory Postsynaptic Potentials
MH - Gene Targeting
MH - *Genetic Predisposition to Disease
MH - Hippocampus/drug effects/*physiopathology
MH - In Situ Hybridization
MH - In Vitro
MH - Kainic Acid
MH - Long-Term Potentiation/genetics
MH - Maze Learning
MH - Mice
MH - Mice, Inbred C57BL
MH - Mice, Knockout
MH - Proto-Oncogene Proteins c-fos/biosynthesis/genetics
MH - RNA, Messenger/biosynthesis
MH - Seizures/chemically induced/*genetics/*physiopathology
MH - Serine Endopeptidases/deficiency/*genetics
MH - Stem Cells
MH - Support, Non-U.S. Gov't
EDAT- 2001/09/11 10:00
MHDA- 2001/10/05 10:01
AID - 21/18/6993 [pii]
URLF- http://www.jneurosci.org/cgi/content/full/21/18/6993
URLS- http://www.jneurosci.org/cgi/content/abstract/21/18/6993
PST - ppublish
SO - J Neurosci 2001 Sep 15;21(18):6993-7000.