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

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 CaMKII╬▒ and phospho-CDK5. These data suggest that Valsartan may promote spinogenesis by enhancing AMPA receptor trafficking and synaptic plasticity signaling.

Pubmed ID: 24012668 RIS Download

Mesh terms: Animals | Antihypertensive Agents | Calcium-Calmodulin-Dependent Protein Kinase Type 2 | Cyclin-Dependent Kinase 5 | Dendritic Spines | Hippocampus | Phosphorylation | Protein Transport | Rats | Rats, Wistar | Receptors, AMPA | Synaptophysin | Tetrazoles | Valine | Valsartan

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Associated grants

  • Agency: NIA NIH HHS, Id: R03 AG039708
  • Agency: NIA NIH HHS, Id: AG039708

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