Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics
Abstract Aim The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain‐derive...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-12-01
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| Series: | Neuropsychopharmacology Reports |
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| Online Access: | https://doi.org/10.1002/npr2.12208 |
| _version_ | 1811177977709330432 |
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| author | Hisatsugu Koshimizu Hidetada Matsuoka Yoshihiro Nakajima Anna Kawai Junichiro Ono Ken‐ichi Ohta Takanori Miki Masataka Sunagawa Naoki Adachi Shingo Suzuki |
| author_facet | Hisatsugu Koshimizu Hidetada Matsuoka Yoshihiro Nakajima Anna Kawai Junichiro Ono Ken‐ichi Ohta Takanori Miki Masataka Sunagawa Naoki Adachi Shingo Suzuki |
| author_sort | Hisatsugu Koshimizu |
| collection | DOAJ |
| description | Abstract Aim The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain‐derived neurotrophic factor (BDNF) plays multiple roles in the central nervous system, and striatal BDNF has been suggested to be involved in psychiatric and neurodegenerative disorders. However, the transcriptomic impact of BDNF on the striatum remains largely unknown. In the present study, we performed transcriptomic profiling of striatal cells stimulated with BDNF to identify enriched gene sets (GSs) and their novel target genes in vitro. Methods We carried out RNA sequencing (RNA‐Seq) of messenger RNA extracted from primary dissociated cultures of rat striatum stimulated with BDNF and conducted Generally Applicable Gene‐set Enrichment (GAGE) analysis on 10599 genes. Significant differentially expressed genes (DEGs) were determined by differential expression analysis for sequence count data 2 (DESeq2). Results GAGE analysis identified significantly enriched GSs that included GSs related to regulation and dysregulation of synaptic functions, such as synaptic vesicle cycle and addiction to nicotine and morphine, respectively. It also detected GSs related to various types of synapses, including not only GABAergic and cholinergic synapses but also dopaminergic and glutamatergic synapses. DESeq2 revealed 72 significant DEGs, among which the highest significance was observed in the apolipoprotein L domain containing 1 (Apold1). Conclusions The present study indicates that BDNF predominantly regulates the expression of synaptic‐function‐related genes and that BDNF promotes synaptogenesis in various subtypes of neurons in the developing striatum. Apold1 may represent a unique target gene of BDNF in the striatum. |
| first_indexed | 2024-04-11T06:10:30Z |
| format | Article |
| id | doaj.art-1a4e258494744e31b10e04d676541b43 |
| institution | Directory Open Access Journal |
| issn | 2574-173X |
| language | English |
| last_indexed | 2024-04-11T06:10:30Z |
| publishDate | 2021-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neuropsychopharmacology Reports |
| spelling | doaj.art-1a4e258494744e31b10e04d676541b432022-12-22T04:41:16ZengWileyNeuropsychopharmacology Reports2574-173X2021-12-0141448549510.1002/npr2.12208Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomicsHisatsugu Koshimizu0Hidetada Matsuoka1Yoshihiro Nakajima2Anna Kawai3Junichiro Ono4Ken‐ichi Ohta5Takanori Miki6Masataka Sunagawa7Naoki Adachi8Shingo Suzuki9Institute for Comprehensive Medical Science Fujita Health University Toyoake JapanDepartment of Pharmaceutical Science Yokohama University of Pharmacy Yokohama JapanHealth Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Takamatsu JapanDepartment of Anatomy and Neurobiology Faculty of Medicine Kagawa University Kagawa JapanDepartment of Anatomy and Neurobiology Faculty of Medicine Kagawa University Kagawa JapanDepartment of Anatomy and Neurobiology Faculty of Medicine Kagawa University Kagawa JapanDepartment of Anatomy and Neurobiology Faculty of Medicine Kagawa University Kagawa JapanDepartment of Physiology Showa University School of Medicine Tokyo JapanDepartment of Physiology Showa University School of Medicine Tokyo JapanHealth Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Takamatsu JapanAbstract Aim The striatum, a main component of the basal ganglia, is a critical part of the motor and reward systems of the brain. It consists of GABAergic and cholinergic neurons and receives projections of dopaminergic, glutamatergic, and serotonergic neurons from other brain regions. Brain‐derived neurotrophic factor (BDNF) plays multiple roles in the central nervous system, and striatal BDNF has been suggested to be involved in psychiatric and neurodegenerative disorders. However, the transcriptomic impact of BDNF on the striatum remains largely unknown. In the present study, we performed transcriptomic profiling of striatal cells stimulated with BDNF to identify enriched gene sets (GSs) and their novel target genes in vitro. Methods We carried out RNA sequencing (RNA‐Seq) of messenger RNA extracted from primary dissociated cultures of rat striatum stimulated with BDNF and conducted Generally Applicable Gene‐set Enrichment (GAGE) analysis on 10599 genes. Significant differentially expressed genes (DEGs) were determined by differential expression analysis for sequence count data 2 (DESeq2). Results GAGE analysis identified significantly enriched GSs that included GSs related to regulation and dysregulation of synaptic functions, such as synaptic vesicle cycle and addiction to nicotine and morphine, respectively. It also detected GSs related to various types of synapses, including not only GABAergic and cholinergic synapses but also dopaminergic and glutamatergic synapses. DESeq2 revealed 72 significant DEGs, among which the highest significance was observed in the apolipoprotein L domain containing 1 (Apold1). Conclusions The present study indicates that BDNF predominantly regulates the expression of synaptic‐function‐related genes and that BDNF promotes synaptogenesis in various subtypes of neurons in the developing striatum. Apold1 may represent a unique target gene of BDNF in the striatum.https://doi.org/10.1002/npr2.12208Apold1BDNFDESeq2GAGERNA‐Seqstriatum |
| spellingShingle | Hisatsugu Koshimizu Hidetada Matsuoka Yoshihiro Nakajima Anna Kawai Junichiro Ono Ken‐ichi Ohta Takanori Miki Masataka Sunagawa Naoki Adachi Shingo Suzuki Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics Neuropsychopharmacology Reports Apold1 BDNF DESeq2 GAGE RNA‐Seq striatum |
| title | Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics |
| title_full | Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics |
| title_fullStr | Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics |
| title_full_unstemmed | Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics |
| title_short | Brain‐derived neurotrophic factor predominantly regulates the expression of synapse‐related genes in the striatum: Insights from in vitro transcriptomics |
| title_sort | brain derived neurotrophic factor predominantly regulates the expression of synapse related genes in the striatum insights from in vitro transcriptomics |
| topic | Apold1 BDNF DESeq2 GAGE RNA‐Seq striatum |
| url | https://doi.org/10.1002/npr2.12208 |
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