Soluble Guanylate Cyclase Stimulator Vericiguat Enhances Long-Term Memory in Rats without Altering Cerebral Blood...

Area of Science:

• Neuroscience
• Pharmacology
• Cardiovascular Science

Background:

• Vascular cognitive impairment (VCI) involves impaired cerebral blood flow, endothelial function, and blood-brain barrier (BBB) integrity.
• The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathway regulates these processes and is crucial for memory formation via long-term potentiation (LTP).

Purpose of the Study:

• To investigate the potential of the sGC stimulator vericiguat as a cognitive enhancer for VCI.
• To assess vericiguat's effects on long-term memory, hippocampal plasticity, and physiological parameters in a rat model.

Main Methods:

• Long-term memory was evaluated using an object location task in rats.
• Hippocampal plasticity was assessed ex vivo using a chemical LTP model.
• Peripheral effects were measured by monitoring blood pressure and cerebral blood volume.

Main Results:

• Vericiguat enhanced long-term memory and hippocampal plasticity, evidenced by increased AMPA receptor translocation.
• The drug did not significantly alter blood pressure or cerebral blood volume.
• Low brain-penetrance of vericiguat was observed.

Conclusions:

• sGC stimulation with vericiguat shows promise as a therapeutic strategy for VCI.
• Memory enhancement may stem from peripheral effects on cerebral microvasculature, especially beneficial in cases of reduced BBB integrity.