title: Prolyl endopeptidase-deficient mice have reduced synaptic spine density in the CA1 region of the hippocampus, impaired LTP, and spatial learning and memory.
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.
authors: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Giuseppe
authors: G
authors: D'Agostino
authors: Jung Dae
authors: JD
authors: Kim
authors: Zhong-Wu
authors: ZW
authors: Liu
authors: Jin Kwon
authors: JK
authors: Jeong
authors: Shigetomo
authors: S
authors: Suyama
authors: Antonio
authors: A
authors: Calignano
authors: Xiao-Bing
authors: XB
authors: Gao
authors: Michael
authors: M
authors: Schwartz
authors: Sabrina
authors: S
authors: Diano
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000502:physiology / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000648:ultrastructure*; D055785:Gene Knockdown Techniques; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D008568:Memory / Q000502:physiology*; D051379:Mice; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D013569:Synapses / Q000648:ultrastructure*
chemical_list: D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases