Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/141808
Title: The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior
Author: Reumann, Rebecca
Vierk, Ricardo
Zhou, Lepu
Gries, Frederice
Kraus, Vanessa
Mienert, Julia
Romswinkel, Eva
Morellini, Fabio
Ferrer, Isidro (Ferrer Abizanda)
Nicolini, Chiara
Fahnestock, Margaret
Rune, Gabriele
Glatzel, Markus
Galliciotti, Giovanna
Keywords: Expressió gènica
Genètica
Neuropèptids
Metabolisme
Sinapsi
Comportament col·lectiu
Gene expression
Genetics
Neuropeptides
Metabolism
Synapses
Collective behavior
Issue Date: 15-Nov-2017
Publisher: Cold Spring Harbor Laboratory Press
Abstract: The serine protease inhibitor neuroserpin regulates the activity of tissue-type plasminogen activator (tPA) in the nervous system. Neuroserpin expression is particularly prominent at late stages of neuronal development in most regions of the central nervous system (CNS), whereas it is restricted to regions related to learning and memory in the adult brain. The physiological expression pattern of neuroserpin, its high degree of colocalization with tPA within the CNS, together with its dysregulation in neuropsychiatric disorders, suggest a role in formation and refinement of synapses. In fact, studies in cell culture and mice point to a role for neuroserpin in dendritic branching, spine morphology, and modulation of behavior. In this study, we investigated the physiological role of neuroserpin in the regulation of synaptic density, synaptic plasticity, and behavior in neuroserpin-deficient mice. In the absence of neuroserpin, mice show a significant decrease in spine-synapse density in the CA1 region of the hippocampus, while expression of the key postsynaptic scaffold protein PSD-95 is increased in this region. Neuroserpin-deficient mice show decreased synaptic potentiation, as indicated by reduced long-term potentiation (LTP), whereas presynaptic paired-pulse facilitation (PPF) is unaffected. Consistent with altered synaptic plasticity, neuroserpin-deficient mice exhibit cognitive and sociability deficits in behavioral assays. However, although synaptic dysfunction is implicated in neuropsychiatric disorders, we do not detect alterations in expression of neuroserpin in fusiform gyrus of autism patients or in dorsolateral prefrontal cortex of schizophrenia patients. Our results identify neuroserpin as a modulator of synaptic plasticity, and point to a role for neuroserpin in learning and memory.
Note: Reproducció del document publicat a: https://doi.org/10.1101/lm.045864.117
It is part of: Learning & Memory, 2017, vol. 24, num. 12, p. 650-659
URI: http://hdl.handle.net/2445/141808
Related resource: https://doi.org/10.1101/lm.045864.117
ISSN: 1072-0502
Appears in Collections:Articles publicats en revistes (Patologia i Terapèutica Experimental)

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