title: 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.affiliation: Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
authors.forename: Young In
authors.initials: YI
authors.lastname: Sohn
authors.forename: Nathanael J
authors.initials: NJ
authors.lastname: Lee
authors.forename: Andrew
authors.initials: A
authors.lastname: Chung
authors.forename: Juan M
authors.initials: JM
authors.lastname: Saavedra
authors.forename: R
authors.initials: R
authors.lastname: Scott Turner
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
authors.forename: Hyang-Sook
authors.initials: HS
authors.lastname: Hoe
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism*; D016708:Synaptophysin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D000959:Antihypertensive Agents; D018091:Receptors, AMPA; D016708:Synaptophysin; D013777:Tetrazoles; D000068756:Valsartan; D051360:Cyclin-Dependent Kinase 5; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D014633:Valine
keywords: AMPA receptor; CaMKIIα; Spinogenesis; Valsartan