Hypertension-Induced Neurovascular and Cognitive Dysfunction at Single-Cell Resolution.

Area of Science:

• Neuroscience
• Cardiovascular Science
• Genomics

Background:

• Arterial hypertension is a major cause of cognitive decline.
• The molecular mechanisms linking hypertension to brain cell dysfunction are not fully understood.

Purpose of the Study:

• To investigate the early transcriptomic changes in the neocortex of a mouse model of hypertension.
• To identify molecular mechanisms underlying hypertension-induced neurovascular and cognitive deficits.

Main Methods:

• Single-cell RNA sequencing (scRNA-seq) was employed.
• Transcriptomic changes were analyzed in a mouse model of angiotensin II-induced hypertension at 3 and 42 days.

Main Results:

• Early signs of endothelial transport disruption, senescence, and oligodendrocyte differentiation stall were observed within 3 days.
• Interneuronal hypofunction and network imbalance were detected early.
• By 42 days, deficits in myelination, axonal conduction, and neuronal mitochondrial dysfunction were evident, coinciding with cognitive impairment.

Conclusions:

• Hypertension causes early vulnerability in endothelial cells, interneurons, and oligodendrocytes.
• These early molecular changes provide a basis for subsequent neurovascular dysfunction and cognitive impairment.
• The study provides a valuable dataset for future research on hypertension and brain health.