Hypertension-induced neurovascular and cognitive dysfunction at single-cell resolution.

Area of Science:

• Neuroscience
• Cardiovascular Science
• Genomics

Background:

• Hypertension is a major cause of cognitive impairment.
• The precise cellular mechanisms by which hypertension affects the brain are not fully understood.
• Angiotensin II plays a role in human hypertension and cerebrovascular changes.

Purpose of the Study:

• To investigate the transcriptomic changes in the neocortex of a mouse model of hypertension.
• To identify early cellular vulnerabilities and molecular pathways affected by hypertension.
• To understand the progression of neurovascular and cognitive deficits.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was employed in a mouse model of angiotensin II-induced hypertension.
• Transcriptomic profiles were analyzed at early (3 days) and later (42 days) time points relative to deficit onset.
• Cellular changes were correlated with neurovascular and cognitive outcomes.

Main Results:

• Early hypertension (3 days) induced endothelial cell transport disruption and senescence, stalled oligodendrocyte differentiation, and interneuronal hypofunction.
• These early changes were linked to angiotensin II signaling.
• Later hypertension (42 days) showed deficits in myelination, axonal conduction, and neuronal mitochondrial dysfunction, coinciding with cognitive impairment.

Conclusions:

• Hypertension causes early, previously unrecognized vulnerability in endothelial cells, interneurons, and oligodendrocytes.
• These early cellular changes provide a molecular basis for later neurovascular dysfunction and cognitive impairment.
• The study offers valuable data for future research into hypertension-related brain damage and therapeutic targets.