Distinct roles of Bdnf I and Bdnf IV transcript variant expression in hippocampal neurons.
| Title: | Distinct roles of Bdnf I and Bdnf IV transcript variant expression in hippocampal neurons. |
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| Authors: | Bach, Svitlana V., Bauman, Allison J., Hosein, Darya, Tuscher, Jennifer J., Ianov, Lara, Greathouse, Kelsey M., Henderson, Benjamin W., Herskowitz, Jeremy H., Martinowich, Keri, Day, Jeremy J. |
| Source: | Hippocampus; May2024, Vol. 34 Issue 5, p218-229, 12p |
| Subject Terms: | GENE expression, BRAIN-derived neurotrophic factor, DENDRITIC spines, HIPPOCAMPUS (Brain), NEUROPLASTICITY, NEURAL development |
| Abstract: | Brain‐derived neurotrophic factor (Bdnf) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well as learning and memory. The rodent Bdnf gene contains nine 5′ non‐coding exons (I–IXa), which are spliced to a common 3′ coding exon (IX). Transcription of individual Bdnf variants, which all encode the same BDNF protein, is initiated at unique promoters upstream of each non‐coding exon, enabling precise spatiotemporal and activity‐dependent regulation of Bdnf expression. Although prior evidence suggests that Bdnf transcripts containing exon I (Bdnf I) or exon IV (Bdnf IV) are uniquely regulated by neuronal activity, the functional significance of different Bdnf transcript variants remains unclear. To investigate functional roles of activity‐dependent Bdnf I and IV transcripts, we used a CRISPR activation system in which catalytically dead Cas9 fused to a transcriptional activator (VPR) is targeted to individual Bdnf promoters with single guide RNAs, resulting in transcript‐specific Bdnf upregulation. Bdnf I upregulation is associated with gene expression changes linked to dendritic growth, while Bdnf IV upregulation is associated with genes that regulate protein catabolism. Upregulation of Bdnf I, but not Bdnf IV, increased mushroom spine density, volume, length, and head diameter, and also produced more complex dendritic arbors in cultured rat hippocampal neurons. In contrast, upregulation of Bdnf IV, but not Bdnf I, in the rat hippocampus attenuated contextual fear expression. Our data suggest that while Bdnf I and IV are both activity‐dependent, BDNF produced from these promoters may serve unique cellular, synaptic, and behavioral functions. [ABSTRACT FROM AUTHOR] |
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| Database: | Complementary Index |
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| Items | – Name: Title Label: Title Group: Ti Data: Distinct roles of Bdnf I and Bdnf IV transcript variant expression in hippocampal neurons. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Bach%2C+Svitlana+V%2E%22">Bach, Svitlana V.</searchLink><br /><searchLink fieldCode="AR" term="%22Bauman%2C+Allison+J%2E%22">Bauman, Allison J.</searchLink><br /><searchLink fieldCode="AR" term="%22Hosein%2C+Darya%22">Hosein, Darya</searchLink><br /><searchLink fieldCode="AR" term="%22Tuscher%2C+Jennifer+J%2E%22">Tuscher, Jennifer J.</searchLink><br /><searchLink fieldCode="AR" term="%22Ianov%2C+Lara%22">Ianov, Lara</searchLink><br /><searchLink fieldCode="AR" term="%22Greathouse%2C+Kelsey+M%2E%22">Greathouse, Kelsey M.</searchLink><br /><searchLink fieldCode="AR" term="%22Henderson%2C+Benjamin+W%2E%22">Henderson, Benjamin W.</searchLink><br /><searchLink fieldCode="AR" term="%22Herskowitz%2C+Jeremy+H%2E%22">Herskowitz, Jeremy H.</searchLink><br /><searchLink fieldCode="AR" term="%22Martinowich%2C+Keri%22">Martinowich, Keri</searchLink><br /><searchLink fieldCode="AR" term="%22Day%2C+Jeremy+J%2E%22">Day, Jeremy J.</searchLink> – Name: TitleSource Label: Source Group: Src Data: Hippocampus; May2024, Vol. 34 Issue 5, p218-229, 12p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22GENE+expression%22">GENE expression</searchLink><br /><searchLink fieldCode="DE" term="%22BRAIN-derived+neurotrophic+factor%22">BRAIN-derived neurotrophic factor</searchLink><br /><searchLink fieldCode="DE" term="%22DENDRITIC+spines%22">DENDRITIC spines</searchLink><br /><searchLink fieldCode="DE" term="%22HIPPOCAMPUS+%28Brain%29%22">HIPPOCAMPUS (Brain)</searchLink><br /><searchLink fieldCode="DE" term="%22NEUROPLASTICITY%22">NEUROPLASTICITY</searchLink><br /><searchLink fieldCode="DE" term="%22NEURAL+development%22">NEURAL development</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: Brain‐derived neurotrophic factor (Bdnf) plays a critical role in brain development, dendritic growth, synaptic plasticity, as well as learning and memory. The rodent Bdnf gene contains nine 5′ non‐coding exons (I–IXa), which are spliced to a common 3′ coding exon (IX). Transcription of individual Bdnf variants, which all encode the same BDNF protein, is initiated at unique promoters upstream of each non‐coding exon, enabling precise spatiotemporal and activity‐dependent regulation of Bdnf expression. Although prior evidence suggests that Bdnf transcripts containing exon I (Bdnf I) or exon IV (Bdnf IV) are uniquely regulated by neuronal activity, the functional significance of different Bdnf transcript variants remains unclear. To investigate functional roles of activity‐dependent Bdnf I and IV transcripts, we used a CRISPR activation system in which catalytically dead Cas9 fused to a transcriptional activator (VPR) is targeted to individual Bdnf promoters with single guide RNAs, resulting in transcript‐specific Bdnf upregulation. Bdnf I upregulation is associated with gene expression changes linked to dendritic growth, while Bdnf IV upregulation is associated with genes that regulate protein catabolism. Upregulation of Bdnf I, but not Bdnf IV, increased mushroom spine density, volume, length, and head diameter, and also produced more complex dendritic arbors in cultured rat hippocampal neurons. In contrast, upregulation of Bdnf IV, but not Bdnf I, in the rat hippocampus attenuated contextual fear expression. Our data suggest that while Bdnf I and IV are both activity‐dependent, BDNF produced from these promoters may serve unique cellular, synaptic, and behavioral functions. [ABSTRACT FROM AUTHOR] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Hippocampus is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
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| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1002/hipo.23600 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 12 StartPage: 218 Subjects: – SubjectFull: GENE expression Type: general – SubjectFull: BRAIN-derived neurotrophic factor Type: general – SubjectFull: DENDRITIC spines Type: general – SubjectFull: HIPPOCAMPUS (Brain) Type: general – SubjectFull: NEUROPLASTICITY Type: general – SubjectFull: NEURAL development Type: general Titles: – TitleFull: Distinct roles of Bdnf I and Bdnf IV transcript variant expression in hippocampal neurons. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Bach, Svitlana V. – PersonEntity: Name: NameFull: Bauman, Allison J. – PersonEntity: Name: NameFull: Hosein, Darya – PersonEntity: Name: NameFull: Tuscher, Jennifer J. – PersonEntity: Name: NameFull: Ianov, Lara – PersonEntity: Name: NameFull: Greathouse, Kelsey M. – PersonEntity: Name: NameFull: Henderson, Benjamin W. – PersonEntity: Name: NameFull: Herskowitz, Jeremy H. – PersonEntity: Name: NameFull: Martinowich, Keri – PersonEntity: Name: NameFull: Day, Jeremy J. IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 05 Text: May2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 10509631 Numbering: – Type: volume Value: 34 – Type: issue Value: 5 Titles: – TitleFull: Hippocampus Type: main |
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