Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory
Document Type
Journal Article
Publication Date
8-1-2013
Journal
Cerebral Cortex
Volume
23
Issue
8
DOI
10.1093/cercor/bhs199
Keywords
CA1; hippocampus; long-term potentiation; prolyl endopeptidase; synaptic spines
Abstract
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. © 2012 © The Author 2012. Published by Oxford University Press. All rights reserved.
APA Citation
D'Agostino, G., Kim, J., Liu, Z., Jeong, J., Suyama, S., Calignano, A., Gao, X., Schwartz, M., & Diano, S. (2013). Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory. Cerebral Cortex, 23 (8). http://dx.doi.org/10.1093/cercor/bhs199