The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior

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The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior. / Reumann, Rebecca; Vierk, Ricardo; Zhou, Lepu; Gries, Frederice; Kraus, Vanessa; Mienert, Julia; Romswinkel, Eva; Morellini, Fabio; Ferrer, Isidre; Nicolini, Chiara; Fahnestock, Margaret; Rune, Gabriele; Glatzel, Markus; Galliciotti, Giovanna.

in: LEARN MEMORY, Jahrgang 24, Nr. 12, 12.2017, S. 650-659.

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@article{8957dbd8335b47d9a1db8e682ca2c149,
title = "The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior",
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.",
keywords = "Journal Article",
author = "Rebecca Reumann and Ricardo Vierk and Lepu Zhou and Frederice Gries and Vanessa Kraus and Julia Mienert and Eva Romswinkel and Fabio Morellini and Isidre Ferrer and Chiara Nicolini and Margaret Fahnestock and Gabriele Rune and Markus Glatzel and Giovanna Galliciotti",
note = "{\textcopyright} 2017 Reumann et al.; Published by Cold Spring Harbor Laboratory Press.",
year = "2017",
month = dec,
doi = "10.1101/lm.045864.117",
language = "English",
volume = "24",
pages = "650--659",
journal = "LEARN MEMORY",
issn = "1072-0502",
publisher = "Cold Spring Harbor Laboratory Press",
number = "12",

}

RIS

TY - JOUR

T1 - The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior

AU - Reumann, Rebecca

AU - Vierk, Ricardo

AU - Zhou, Lepu

AU - Gries, Frederice

AU - Kraus, Vanessa

AU - Mienert, Julia

AU - Romswinkel, Eva

AU - Morellini, Fabio

AU - Ferrer, Isidre

AU - Nicolini, Chiara

AU - Fahnestock, Margaret

AU - Rune, Gabriele

AU - Glatzel, Markus

AU - Galliciotti, Giovanna

N1 - © 2017 Reumann et al.; Published by Cold Spring Harbor Laboratory Press.

PY - 2017/12

Y1 - 2017/12

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1101/lm.045864.117

DO - 10.1101/lm.045864.117

M3 - SCORING: Journal article

C2 - 29142062

VL - 24

SP - 650

EP - 659

JO - LEARN MEMORY

JF - LEARN MEMORY

SN - 1072-0502

IS - 12

ER -