Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions
Mental stress modifies both cholinergic neurotransmission and alternative splicing in the brain, via incompletely understood mechanisms. Here, we report that stress changes brain microRNA (miR) expression and that some of these stress-regulated miRs regulate alternative splicing. Acute and chronic i...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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Springer-Verlag
2013
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| Online Access: | http://hdl.handle.net/1721.1/82659 |
| _version_ | 1826206538782474240 |
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| author | Meerson, Ari Cacheaux, Luisa Goosens, Ki Ann Sapolsky, Robert M. Soreq, Hermona Kaufer, Daniela |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Meerson, Ari Cacheaux, Luisa Goosens, Ki Ann Sapolsky, Robert M. Soreq, Hermona Kaufer, Daniela |
| author_sort | Meerson, Ari |
| collection | MIT |
| description | Mental stress modifies both cholinergic neurotransmission and alternative splicing in the brain, via incompletely understood mechanisms. Here, we report that stress changes brain microRNA (miR) expression and that some of these stress-regulated miRs regulate alternative splicing. Acute and chronic immobilization stress differentially altered the expression of numerous miRs in two stress-responsive regions of the rat brain, the hippocampal CA1 region and the central nucleus of the amygdala. miR-134 and miR-183 levels both increased in the amygdala following acute stress, compared to unstressed controls. Chronic stress decreased miR-134 levels, whereas miR-183 remained unchanged in both the amygdala and CA1. Importantly, miR-134 and miR-183 share a common predicted mRNA target, encoding the splicing factor SC35. Stress was previously shown to upregulate SC35, which promotes the alternative splicing of acetylcholinesterase (AChE) from the synapse-associated isoform AChE-S to the, normally rare, soluble AChE-R protein. Knockdown of miR-183 expression increased SC35 protein levels in vitro, whereas overexpression of miR-183 reduced SC35 protein levels, suggesting a physiological role for miR-183 regulation under stress. We show stress-induced changes in miR-183 and miR-134 and suggest that, by regulating splicing factors and their targets, these changes modify both alternative splicing and cholinergic neurotransmission in the stressed brain. |
| first_indexed | 2024-09-23T13:34:31Z |
| format | Article |
| id | mit-1721.1/82659 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:34:31Z |
| publishDate | 2013 |
| publisher | Springer-Verlag |
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| spelling | mit-1721.1/826592022-10-01T15:44:06Z Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions Meerson, Ari Cacheaux, Luisa Goosens, Ki Ann Sapolsky, Robert M. Soreq, Hermona Kaufer, Daniela Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences McGovern Institute for Brain Research at MIT Goosens, Ki Ann Mental stress modifies both cholinergic neurotransmission and alternative splicing in the brain, via incompletely understood mechanisms. Here, we report that stress changes brain microRNA (miR) expression and that some of these stress-regulated miRs regulate alternative splicing. Acute and chronic immobilization stress differentially altered the expression of numerous miRs in two stress-responsive regions of the rat brain, the hippocampal CA1 region and the central nucleus of the amygdala. miR-134 and miR-183 levels both increased in the amygdala following acute stress, compared to unstressed controls. Chronic stress decreased miR-134 levels, whereas miR-183 remained unchanged in both the amygdala and CA1. Importantly, miR-134 and miR-183 share a common predicted mRNA target, encoding the splicing factor SC35. Stress was previously shown to upregulate SC35, which promotes the alternative splicing of acetylcholinesterase (AChE) from the synapse-associated isoform AChE-S to the, normally rare, soluble AChE-R protein. Knockdown of miR-183 expression increased SC35 protein levels in vitro, whereas overexpression of miR-183 reduced SC35 protein levels, suggesting a physiological role for miR-183 regulation under stress. We show stress-induced changes in miR-183 and miR-134 and suggest that, by regulating splicing factors and their targets, these changes modify both alternative splicing and cholinergic neurotransmission in the stressed brain. 2013-12-06T15:17:19Z 2013-12-06T15:17:19Z 2009-08 2009-07 Article http://purl.org/eprint/type/JournalArticle 0895-8696 1559-1166 http://hdl.handle.net/1721.1/82659 Meerson, Ari, Luisa Cacheaux, Ki Ann Goosens, Robert M. Sapolsky, Hermona Soreq, and Daniela Kaufer. “Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions.” Journal of Molecular Neuroscience 40, no. 1 2 (January 27, 2010): 47-55. en_US http://dx.doi.org/10.1007/s12031-009-9252-1 Journal of Molecular Neuroscience http://creativecommons.org/licenses/by/3.0/ application/pdf Springer-Verlag PMC |
| spellingShingle | Meerson, Ari Cacheaux, Luisa Goosens, Ki Ann Sapolsky, Robert M. Soreq, Hermona Kaufer, Daniela Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title | Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title_full | Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title_fullStr | Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title_full_unstemmed | Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title_short | Changes in Brain MicroRNAs Contribute to Cholinergic Stress Reactions |
| title_sort | changes in brain micrornas contribute to cholinergic stress reactions |
| url | http://hdl.handle.net/1721.1/82659 |
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