The serine protease inhibitor neuroserpin is required for normal synaptic plasticity and regulates learning and social behavior
| Autor: | Chiara Nicolini, Rebecca Reumann, Lepu Zhou, Julia Mienert, Giovanna Galliciotti, Eva Viktoria Romswinkel, Fabio Morellini, Isidre Ferrer, Frederice Gries, Ricardo Vierk, Gabriele M. Rune, Vanessa Kraus, Markus Glatzel, Margaret Fahnestock |
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| Přispěvatelé: | Universitat de Barcelona |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Nervous system Collective behavior Long-Term Potentiation Hippocampus Mice 0302 clinical medicine Postsynaptic potential Child Neuronal Plasticity Long-term potentiation Middle Aged Metabolisme Neuropsychology and Physiological Psychology medicine.anatomical_structure Adult Serine Proteinase Inhibitors Adolescent Synaptosomal-Associated Protein 25 Cognitive Neuroscience Central nervous system Mice Transgenic Biology Young Adult 03 medical and health sciences Cellular and Molecular Neuroscience Neuroserpin Genetics medicine Animals Humans Comportament col·lectiu Autistic Disorder Maze Learning Social Behavior Serpins Research Neuropeptides Colocalization Expressió gènica Mice Inbred C57BL Neuropèptids Metabolism 030104 developmental biology Gene Expression Regulation Sinapsi Synapses Synaptic plasticity Exploratory Behavior Gene expression Neuroscience Genètica 030217 neurology & neurosurgery |
| Zdroj: | Dipòsit Digital de la UB Universidad de Barcelona Recercat. Dipósit de la Recerca de Catalunya instname |
| ISSN: | 1549-5485 |
| DOI: | 10.1101/lm.045864.117 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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