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

Publication/Presentation Date

10-4-2013

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.

Volume

439

Issue

4

First Page

464

Last Page

470

ISSN

1090-2104

Disciplines

Medicine and Health Sciences

PubMedID

24012668

Department(s)

Department of Medicine

Document Type

Article

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