TY - JOUR
T1 - Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory
AU - D'Agostino, Giuseppe
AU - Kim, Jung Dae
AU - Liu, Zhong-Wu
AU - Jeong, Jin Kwon
AU - Suyama, Shigetomo
AU - Calignano, Antonio
AU - Gao, Xiao-Bing
AU - Schwartz, Michael
AU - Diano, Sabrina
PY - 2013/8
Y1 - 2013/8
N2 - Prolyl endopeptidase (PREP) is a phylogenetically conserved serine protease and, in humans and rodents, is highly expressed in the brain. Several neuropeptides associated with learning and memory and neurodegenerative disorders have been proposed to be the substrates for PREP, suggesting a possible role for PREP in these processes. However, its physiological function remains elusive. Combining genetic, anatomical, electrophysiological, and behavioral approaches, we show that PREP genetrap mice have decreased synaptic spine density in the CA1 region of the hippocampus, reduced hippocampal long-term potentiation, impaired hippocampal-mediated learning and memory, and reduced growth-associated protein-43 levels when compared with wild-type controls. These observations reveal a role for PREP in mediating hippocampal plasticity and spatial memory formation, with implications for its pharmacological manipulation in diseases related to cognitive impairment.
AB - Prolyl endopeptidase (PREP) is a phylogenetically conserved serine protease and, in humans and rodents, is highly expressed in the brain. Several neuropeptides associated with learning and memory and neurodegenerative disorders have been proposed to be the substrates for PREP, suggesting a possible role for PREP in these processes. However, its physiological function remains elusive. Combining genetic, anatomical, electrophysiological, and behavioral approaches, we show that PREP genetrap mice have decreased synaptic spine density in the CA1 region of the hippocampus, reduced hippocampal long-term potentiation, impaired hippocampal-mediated learning and memory, and reduced growth-associated protein-43 levels when compared with wild-type controls. These observations reveal a role for PREP in mediating hippocampal plasticity and spatial memory formation, with implications for its pharmacological manipulation in diseases related to cognitive impairment.
KW - CA1
KW - hippocampus
KW - long-term protection
KW - prolyl endopeptidase
U2 - 10.1093/cercor/bhs199
DO - 10.1093/cercor/bhs199
M3 - Article
C2 - 22767632
SN - 1047-3211
VL - 23
SP - 2007
EP - 2014
JO - Cerebral Cortex
JF - Cerebral Cortex
IS - 8
ER -