Peripheral delivery of a ROCK inhibitor improves learning and working memory.
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.
Huentelman
Matthew J
MJ
Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA. mhuentelman@tgen.org
Stephan
Dietrich A
DA
Talboom
Joshua
J
Corneveaux
Jason J
JJ
Reiman
David M
DM
Gerber
Jill D
JD
Barnes
Carol A
CA
Alexander
Gene E
GE
Reiman
Eric M
EM
Bimonte-Nelson
Heather A
HA
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*
C431085:hydroxyfasudil; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D020742:rhoA GTP-Binding Protein