Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory

Giuseppe D'Agostino, Jung Dae Kim, Zhong-Wu Liu, Jin Kwon Jeong, Shigetomo Suyama, Antonio Calignano, Xiao-Bing Gao, Michael Schwartz, Sabrina Diano

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17 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2007-2014
Number of pages8
JournalCerebral Cortex
Volume23
Issue number8
Early online date5 Jul 2012
DOIs
Publication statusPublished - Aug 2013

Keywords

  • CA1
  • hippocampus
  • long-term protection
  • prolyl endopeptidase

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    D'Agostino, G., Kim, J. D., Liu, Z-W., Jeong, J. K., Suyama, S., Calignano, A., Gao, X-B., 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), 2007-2014. https://doi.org/10.1093/cercor/bhs199