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RNA-Sequencing Analysis Revealed a Distinct Motor Cortex Transcriptome in Spontaneously Recovered Mice After Stroke
Masaki Ito1, Markus Aswendt1, Alex G Lee2
1From the Department of Neurosurgery (M.I., M.A., S.I., Z.C., E.H.W., S.L.L., D.L.S., M.Y.C., G.K.S.).
Stroke
|October 26, 2018
Summary
This study reveals key genes and pathways in the motor cortex involved in natural brain recovery after stroke. Understanding these intrinsic changes, particularly cAMP signaling in the contralesional cortex, offers new therapeutic targets for stroke recovery.
Area of Science:
- Neuroscience
- Genomics
- Stroke Research
Background:
- Therapeutic interventions offer insights into brain repair post-stroke.
- Intrinsic molecular changes during spontaneous stroke recovery remain less understood.
Purpose of the Study:
- To identify intrinsic molecular changes in the primary motor cortex during spontaneous stroke recovery.
- To investigate the transcriptome of mice exhibiting natural recovery after stroke.
Main Methods:
- Transient middle cerebral artery occlusion in male C57BL/6J mice.
- Functional assessment using the horizontal rotating beam test and detailed lesion mapping.
- RNA-sequencing transcriptome analysis of ipsilesional and contralesional primary motor cortices (iM1 and cM1).
Main Results:
- Two distinct recovery groups (spontaneously recovered and nonrecovered) identified, with similar lesion profiles.
- Distinct biological pathways identified in iM1 and cM1 of recovered mice.
- Correlation analysis revealed 38 genes in iM1 and 74 genes in cM1 linked to recovery, highlighting cAMP signaling (Adora2a, Drd2, Pde10a) in cM1.
Conclusions:
- RNA-sequencing identified novel recovery-related genes in the motor cortex of spontaneously recovered stroke mice.
- The contralesional cortex plays a significant role in spontaneous stroke recovery.
- Targeting Adora2a, Drd2, and Pde10a-mediated cAMP signaling in the contralesional cortex may enhance stroke recovery outcomes.
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