Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking.

Abstract

Recent studies demonstrated that the antihypertensive drug Valsartan improved spatial and episodic memory in mouse models of Alzheimer's Disease (AD) and human subjects with hypertension. However, the molecular mechanism by which Valsartan can regulate cognitive function is still unknown. Here, we investigated the effect of Valsartan on dendritic spine formation in primary hippocampal neurons, which is correlated with learning and memory. Interestingly, we found that Valsartan promotes spinogenesis in developing and mature neurons. In addition, we found that Valsartan increases the puncta number of PSD-95 and trends toward an increase in the puncta number of synaptophysin. Moreover, Valsartan increased the cell surface levels of AMPA receptors and selectively altered the levels of spinogenesis-related proteins, including CaMKIIα and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling.

• Authors: Young In Sohn, Nathanael J Lee, Andrew Chung, Juan M Saavedra, R Scott Turner, Daniel T S Pak, Hyang-Sook Hoe
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 439 Issue 4 Pg. 464-70 (Oct 04 2013) ISSN: 1090-2104 [Electronic] United States
• PMID: 24012668 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Antihypertensive Agents
• Receptors, AMPA
• Synaptophysin
• Tetrazoles
• Valsartan
• Cyclin-Dependent Kinase 5
• Calcium-Calmodulin-Dependent Protein Kinase Type 2
• Valine

Topics

• Animals
• Antihypertensive Agents (pharmacology)
• Calcium-Calmodulin-Dependent Protein Kinase Type 2 (metabolism)
• Cyclin-Dependent Kinase 5 (metabolism)
• Dendritic Spines (drug effects, metabolism, ultrastructure)
• Hippocampus (drug effects, metabolism, ultrastructure)
• Phosphorylation
• Protein Transport
• Rats
• Rats, Wistar
• Receptors, AMPA (metabolism)
• Synaptophysin (metabolism)
• Tetrazoles (pharmacology)
• Valine (analogs & derivatives, pharmacology)
• Valsartan