Improved dynamic monitoring of transcriptional activity during longitudinal analysis in the mouse brain

Bioluminescence imaging has proven to be a highly sensitive technique for assessing transcriptional activity toward understanding gene regulation patterns; however, application of this technique is limited for brain research. In particular, the poor spatiotemporal resolution is a major hurdle for mo...

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Bibliographic Details
Published in:Biology open 2019-01, Vol.8 (1)
Main Authors: Heo, Hwon, Jo, Juyeong, Jung, Jae In, Han, Young-Min, Lee, Seongsoo, Kim, Song Rae, Kwon, Seung-Hae, Kim, Kil-Nam, Hwang, Byung Joon, Kee, Yun, Lee, Byoung Dae, Kang, Dongmin, Her, Song
Format: Article
Language:English
Subjects:
Bioluminescence
Brain
Brain promoter activity
Brain research
Coefficient of variation
Cortex (temporal)
Gene regulation
Genes
Glucocorticoid receptor signaling
Glucocorticoids
In vivo methods and tests
Longitudinal monitoring
Luciferase
Mental disorders
Methods and Techniques
Monitoring
Neuroimaging
Normal stress
Pin-point monitoring transcription activity
Prefrontal cortex
Science
Stress
Temporal resolution
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Summary:Bioluminescence imaging has proven to be a highly sensitive technique for assessing transcriptional activity toward understanding gene regulation patterns; however, application of this technique is limited for brain research. In particular, the poor spatiotemporal resolution is a major hurdle for monitoring the dynamic changes of transcriptional activity in specific regions of the brain during longitudinal analysis of living animals. To overcome this limitation, in this study, we modified a lentivirus-based luciferase glucocorticoid receptor (GR) reporter by inserting destabilizing sequence genes, and then the reporter was stereotaxically injected in the mouse infralimbic prefrontal cortex (IL-PFC). Using this strategy, we could successfully pin-point and monitor the dynamic changes in GR activity in IL-PFC during normal stress adaptation. The modified reporter showed a 1.5-fold increase in temporal resolution for monitoring GR activity compared to the control, with respect to the intra-individual coefficients of variation. This novel method has broad applications, as it is readily adaptable to different types of transcription factor arrays as well spanning wide target regions of the brain to other organs and tissues.
ISSN:2046-6390
2046-6390
DOI:10.1242/bio.037168