Long Noncoding RNA Fos Downstream Transcript Is Developmentally Dispensable but Vital for Shaping the Poststroke
Suresh L Mehta1, Anil K Chokkalla1,2, TaeHee Kim1
1Department of Neurological Surgery (S.L.M., A.K.C., T.K., S.B., B.C., K.C.M.-B., R.V.), University of Wisconsin-Madison.
Stroke
|May 4, 2021
Summary
Removing the long noncoding RNA Fos downstream transcript (FosDT) in rats improved stroke recovery and reduced brain damage by decreasing inflammation and cell death. FosDT is a promising therapeutic target for stroke.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Stroke triggers the expression of long noncoding RNAs (lncRNAs) in the brain, but their role in post-stroke recovery remains unclear.
- A brain-specific lncRNA, Fos downstream transcript (FosDT), is rapidly induced in rodent brains after focal ischemia.
Purpose of the Study:
- To investigate the functional significance of FosDT in post-stroke brain damage and neurological recovery.
- To evaluate the therapeutic potential of targeting FosDT for stroke treatment.
Main Methods:
- Generated Fos downstream transcript knockout (FosDT−/−) rats using CRISPR-Cas9 genome editing.
- Subjected FosDT−/− and wild-type (FosDT+/+) rats to transient middle cerebral artery occlusion (tMCAO) to model ischemic stroke.
- Assessed sensorimotor deficits, lesion volume, developmental expression, and molecular mechanisms using RNA-sequencing and immunostaining.
Main Results:
- Fos downstream transcript (FosDT) knockout rats exhibited enhanced sensorimotor recovery and reduced brain damage following ischemic stroke.
- Knockout rats showed decreased inflammatory gene induction, apoptosis, mitochondrial dysfunction, and oxidative stress.
- Fos downstream transcript (FosDT) expression is developmentally regulated but dispensable for normal growth and development.
Conclusions:
- Fos downstream transcript (FosDT) plays a critical role in exacerbating ischemic brain damage and hindering neurological recovery.
- Targeting Fos downstream transcript (FosDT) represents a promising therapeutic strategy for reducing stroke-induced brain injury and promoting functional recovery.
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