Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y
Haloperidol is a commonly used antipsychotic drug for treating schizophrenia. Clinical imaging studies have found that haloperidol can cause volume loss of human brain tissue, which is supported by animal studies showing that haloperidol reduces the number of synaptic spines. The mechanism remains u...
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Frontiers Media S.A.
2018-10-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00743/full |
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| author | Minmin Hu Minmin Hu Peng Zheng Yuanyi Xie Zehra Boz Yinghua Yu Renxian Tang Alison Jones Kuiyang Zheng Xu-Feng Huang |
| author_facet | Minmin Hu Minmin Hu Peng Zheng Yuanyi Xie Zehra Boz Yinghua Yu Renxian Tang Alison Jones Kuiyang Zheng Xu-Feng Huang |
| author_sort | Minmin Hu |
| collection | DOAJ |
| description | Haloperidol is a commonly used antipsychotic drug for treating schizophrenia. Clinical imaging studies have found that haloperidol can cause volume loss of human brain tissue, which is supported by animal studies showing that haloperidol reduces the number of synaptic spines. The mechanism remains unknown. Gut microbiota metabolites, short chain fatty acids including propionate, are reported to have neuroprotective effect and influence gene expression. This study aims to investigate the effect and mechanism of propionate in the protection of neurite lesion induced by haloperidol. This study showed that 10 μM haloperidol (clinical relevant dose) impaired neurite length in human blastoma SH-SY5Y cells, which were confirmed by using primary mouse striatal spiny neurons. We found that haloperidol impaired neurite length were accompanied by a decreased neuropeptide Y (NPY) expression, but no effect on GSK3β signaling. Importantly, this project research found that propionate was capable of protecting against haloperidol-induced neurite lesions and preventing NPY reduction. To confirm this finding, we used specific siRNAs targeting NPY which blocked the protective effect of propionate on haloperidol-induced neurite lesions. Furthermore, since NPY is regulated by the nuclear transcription factor CREB, we measured pCREB that was decreased by haloperidol and was normalized by propionate. Therefore, propionate has a protective effect against pCREB-NPY mediated haloperidol-induced neurite lesions. |
| first_indexed | 2024-12-23T11:49:57Z |
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| id | doaj.art-f96dee39480741218e7c181f7e71b9a9 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-23T11:49:57Z |
| publishDate | 2018-10-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-f96dee39480741218e7c181f7e71b9a92022-12-21T17:48:14ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-10-011210.3389/fnins.2018.00743415511Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide YMinmin Hu0Minmin Hu1Peng Zheng2Yuanyi Xie3Zehra Boz4Yinghua Yu5Renxian Tang6Alison Jones7Kuiyang Zheng8Xu-Feng Huang9Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Jiangsu, ChinaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Jiangsu, ChinaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Jiangsu, ChinaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaJiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Jiangsu, ChinaIllawarra Health and Medical Research Institute, School of Medicine, University of Wollongong, Wollongong, NSW, AustraliaHaloperidol is a commonly used antipsychotic drug for treating schizophrenia. Clinical imaging studies have found that haloperidol can cause volume loss of human brain tissue, which is supported by animal studies showing that haloperidol reduces the number of synaptic spines. The mechanism remains unknown. Gut microbiota metabolites, short chain fatty acids including propionate, are reported to have neuroprotective effect and influence gene expression. This study aims to investigate the effect and mechanism of propionate in the protection of neurite lesion induced by haloperidol. This study showed that 10 μM haloperidol (clinical relevant dose) impaired neurite length in human blastoma SH-SY5Y cells, which were confirmed by using primary mouse striatal spiny neurons. We found that haloperidol impaired neurite length were accompanied by a decreased neuropeptide Y (NPY) expression, but no effect on GSK3β signaling. Importantly, this project research found that propionate was capable of protecting against haloperidol-induced neurite lesions and preventing NPY reduction. To confirm this finding, we used specific siRNAs targeting NPY which blocked the protective effect of propionate on haloperidol-induced neurite lesions. Furthermore, since NPY is regulated by the nuclear transcription factor CREB, we measured pCREB that was decreased by haloperidol and was normalized by propionate. Therefore, propionate has a protective effect against pCREB-NPY mediated haloperidol-induced neurite lesions.https://www.frontiersin.org/article/10.3389/fnins.2018.00743/fullantipsychotic drughaloperidolneurite impairmentpropionateneuropeptide Y |
| spellingShingle | Minmin Hu Minmin Hu Peng Zheng Yuanyi Xie Zehra Boz Yinghua Yu Renxian Tang Alison Jones Kuiyang Zheng Xu-Feng Huang Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y Frontiers in Neuroscience antipsychotic drug haloperidol neurite impairment propionate neuropeptide Y |
| title | Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y |
| title_full | Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y |
| title_fullStr | Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y |
| title_full_unstemmed | Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y |
| title_short | Propionate Protects Haloperidol-Induced Neurite Lesions Mediated by Neuropeptide Y |
| title_sort | propionate protects haloperidol induced neurite lesions mediated by neuropeptide y |
| topic | antipsychotic drug haloperidol neurite impairment propionate neuropeptide Y |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00743/full |
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