title: Deficiency of prolyl oligopeptidase in mice disturbs synaptic plasticity and reduces anxiety-like behaviour, body weight, and brain volume.
abstract: Prolyl oligopeptidase (PREP) has been implicated in neurodegeneration and neuroinflammation and has been considered a drug target to enhance memory in dementia. However, the true physiological role of PREP is not yet understood. In this paper, we report the phenotyping of a mouse line where the PREP gene has been knocked out. This work indicates that the lack of PREP in mice causes reduced anxiety but also hyperactivity. The cortical volumes of PREP knockout mice were smaller than those of wild type littermates. Additionally, we found increased expression of diazepam binding inhibitor protein in the cortex and of the somatostatin receptor-2 in the hippocampus of PREP knockout mice. Furthermore, immunohistochemistry and tail suspension test revealed lack of response of PREP knockout mice to lipopolysaccharide insult. Further analysis revealed significantly increased levels of polysialylated-neural cell adhesion molecule in PREP deficient mice. These findings might be explained as possible alteration in brain plasticity caused by PREP deficiency, which in turn affect behaviour and brain development.
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Höfling
authors.affiliation: Neuroscience Centre, University of Helsinki, Finland.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kulesskaya
authors.affiliation: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia.
authors.forename: Külli
authors.initials: K
authors.lastname: Jaako
authors.affiliation: Division of Pharmacology and Pharmacotherapy, University of Helsinki, Finland.
authors.forename: Iida
authors.initials: I
authors.lastname: Peltonen
authors.affiliation: Division of Pharmacology and Pharmacotherapy, University of Helsinki, Finland.
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
authors.affiliation: Charles River Drug Discovery Services, Kuopio, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Nurmi
authors.affiliation: Charles River Drug Discovery Services, Kuopio, Finland.
authors.forename: Nina
authors.initials: N
authors.lastname: Vartiainen
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Morawski
authors.affiliation: Department of Pharmacology, Institute of Biomedicine and Translational Medicine, University of Tartu, Estonia.
authors.forename: Alexander
authors.initials: A
authors.lastname: Zharkovsky
authors.affiliation: Neuroscience Centre, University of Helsinki, Finland.
authors.forename: Vootele
authors.initials: V
authors.lastname: Võikar
authors.affiliation: Paul Flechsig Institute for Brain Research, University of Leipzig, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Roßner
authors.affiliation: Division of Pharmacology and Pharmacotherapy, University of Helsinki, Finland. Electronic address: Arturo.Garcia@helsinki.fi.
authors.forename: J Arturo
authors.initials: JA
authors.lastname: García-Horsman
mesh_terms: D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000473:pathology / Q000523:psychology*; D001522:Behavior, Animal; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000473:pathology; D016207:Cytokines / Q000097:blood; D019417:Hindlimb Suspension; D006948:Hyperkinesis / Q000235:genetics / Q000523:psychology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics*; D010641:Phenotype; D000085822:Prolyl Oligopeptidases; D017481:Receptors, Somatostatin / Q000096:biosynthesis / Q000235:genetics; D012697:Serine Endopeptidases / Q000172:deficiency*; D013569:Synapses / Q000235:genetics*
chemical_list: D016207:Cytokines; D017481:Receptors, Somatostatin; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases
keywords: Anxiety; Behaviour; Depression; Prolyl oligopeptidase; Synaptic plasticity