Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice
Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explor...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2017/4526417 |
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| author | Hua Yang Mengjie Zhang Jiahao Shi Yunhe Zhou Zhipeng Wan Yicheng Wang Yinghan Wan Jun Li Zhugang Wang Jian Fei |
| author_facet | Hua Yang Mengjie Zhang Jiahao Shi Yunhe Zhou Zhipeng Wan Yicheng Wang Yinghan Wan Jun Li Zhugang Wang Jian Fei |
| author_sort | Hua Yang |
| collection | DOAJ |
| description | Several studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness. |
| format | Article |
| id | doaj-art-652615ce70664144bdfe7da13257db67 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-652615ce70664144bdfe7da13257db672025-02-03T00:59:14ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/45264174526417Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in MiceHua Yang0Mengjie Zhang1Jiahao Shi2Yunhe Zhou3Zhipeng Wan4Yicheng Wang5Yinghan Wan6Jun Li7Zhugang Wang8Jian Fei9School of Life Science and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Science and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Science and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Science and Technology, Tongji University, Shanghai 200092, ChinaSchool of Life Science and Technology, Tongji University, Shanghai 200092, ChinaShanghai Engineering Research Center of Model Organisms (SRCMO/SMOC), Shanghai 201203, ChinaShanghai Engineering Research Center of Model Organisms (SRCMO/SMOC), Shanghai 201203, ChinaShanghai Engineering Research Center of Model Organisms (SRCMO/SMOC), Shanghai 201203, ChinaShanghai Engineering Research Center of Model Organisms (SRCMO/SMOC), Shanghai 201203, ChinaSchool of Life Science and Technology, Tongji University, Shanghai 200092, ChinaSeveral studies have associated reduced expression of synaptosomal-associated protein of 25 kDa (SNAP-25) with schizophrenia, yet little is known about its role in the illness. In this paper, a forebrain glutamatergic neuron-specific SNAP-25 knockout mouse model was constructed and studied to explore the possible pathogenetic role of SNAP-25 in schizophrenia. We showed that SNAP-25 conditional knockout (cKO) mice exhibited typical schizophrenia-like phenotype. A significantly elevated extracellular glutamate level was detected in the cerebral cortex of the mouse model. Compared with Ctrls, SNAP-25 was dramatically reduced by about 60% both in cytoplasm and in membrane fractions of cerebral cortex of cKOs, while the other two core members of SNARE complex: Syntaxin-1 (increased ~80%) and Vamp2 (increased ~96%) were significantly increased in cell membrane part. Riluzole, a glutamate release inhibitor, significantly attenuated the locomotor hyperactivity deficits in cKO mice. Our findings provide in vivo functional evidence showing a critical role of SNAP-25 dysfunction on synaptic transmission, which contributes to the developmental of schizophrenia. It is suggested that a SNAP-25 cKO mouse, a valuable model for schizophrenia, could address questions regarding presynaptic alterations that contribute to the etiopathophysiology of SZ and help to consummate the pre- and postsynaptic glutamatergic pathogenesis of the illness.http://dx.doi.org/10.1155/2017/4526417 |
| spellingShingle | Hua Yang Mengjie Zhang Jiahao Shi Yunhe Zhou Zhipeng Wan Yicheng Wang Yinghan Wan Jun Li Zhugang Wang Jian Fei Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice Neural Plasticity |
| title | Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice |
| title_full | Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice |
| title_fullStr | Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice |
| title_full_unstemmed | Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice |
| title_short | Brain-Specific SNAP-25 Deletion Leads to Elevated Extracellular Glutamate Level and Schizophrenia-Like Behavior in Mice |
| title_sort | brain specific snap 25 deletion leads to elevated extracellular glutamate level and schizophrenia like behavior in mice |
| url | http://dx.doi.org/10.1155/2017/4526417 |
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