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Transcriptome Profiling of Mouse Corpus Callosum After Cerebral Hypoperfusion
Hajime Takase1, Gen Hamanaka1, Ryo Ohtomo1
1Neuroprotection Research Laboratory, Department of Radiology and Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, United States.
Frontiers in Cell and Developmental Biology
|July 5, 2021
Summary
Subcortical ischemic vascular dementia (SIVD) involves white matter damage. This study reveals activated oligodendrogenesis and angiogenic pathways in a preclinical SIVD model, offering potential therapeutic targets.
Area of Science:
- Neuroscience
- Vascular Biology
- Genomics
Background:
- Subcortical ischemic vascular dementia (SIVD) is the most common form of vascular cognitive impairment and dementia (VCID).
- White matter damage from cerebral hypoperfusion is a key feature of SIVD.
- Effective therapies for SIVD are currently lacking, necessitating research into its pathological mechanisms.
Purpose of the Study:
- To investigate the cellular and molecular changes in the corpus callosum following cerebral hypoperfusion in a preclinical SIVD model.
- To identify potential therapeutic targets for SIVD by analyzing transcriptomic profiles.
Main Methods:
- Cerebral hypoperfusion was induced in mice using bilateral carotid artery stenosis (BCAS).
- Cognitive deficits were assessed using the novel object recognition test.
- RNA sequencing was performed on corpus callosum tissue from sham-operated and BCAS-operated mice.
- Gene set enrichment analysis was conducted on differentially expressed genes.
Main Results:
- BCAS-induced hypoperfusion led to cognitive deficits in mice at 4 weeks post-operation.
- Transcriptomic analysis revealed activation of oligodendrogenesis and angiogenic pathways in the corpus callosum.
- A database of transcriptomic profiles from the SIVD model was generated.
Conclusions:
- The study identified activated oligodendrogenesis and angiogenic responses in the corpus callosum following cerebral hypoperfusion.
- The generated transcriptomic data provides a valuable resource for future research into SIVD.
- These findings may aid in the discovery of novel therapeutic targets for SIVD.

