title: Peripheral delivery of a ROCK inhibitor improves learning and working memory.
abstract: Previously, utilizing a series of genome-wide association, brain imaging, and gene expression studies we implicated the KIBRA gene and the RhoA/ROCK pathway in hippocampal-mediated human memory. Here we show that peripheral administration of the ROCK inhibitor hydroxyfasudil improves spatial learning and working memory in the rodent model. This study supports the action of ROCK on learning and memory, suggests the potential value of ROCK inhibition for the promotion of cognition in humans, and highlights the powerful potential of unbiased genome-wide association studies to inform potential novel uses for existing pharmaceuticals.
authors.affiliation: Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA. mhuentelman@tgen.org
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Huentelman
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
authors.forename: Joshua
authors.initials: J
authors.lastname: Talboom
authors.forename: Jason J
authors.initials: JJ
authors.lastname: Corneveaux
authors.forename: David M
authors.initials: DM
authors.lastname: Reiman
authors.forename: Jill D
authors.initials: JD
authors.lastname: Gerber
authors.forename: Carol A
authors.initials: CA
authors.lastname: Barnes
authors.forename: Gene E
authors.initials: GE
authors.lastname: Alexander
authors.forename: Eric M
authors.initials: EM
authors.lastname: Reiman
authors.forename: Heather A
authors.initials: HA
authors.lastname: Bimonte-Nelson
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000375:Aging; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008570:Memory, Short-Term / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors*
chemical_list: C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020742:rhoA GTP-Binding Protein