title: ROCK inhibition prevents tau hyperphosphorylation and p25/CDK5 increase after global cerebral ischemia.
abstract: Rho-kinase (ROCK) is a downstream effector of RhoA, which has been associated with growth cone collapse and retraction in neurons. ROCK inhibition has been shown to protect against ischemic damage, thereby improving short-term collateral flow, inhibiting platelet aggregation, leukocyte adhesion, and preventing neuronal death. However, little is known about the long-term effects of ROCK inhibition on behavior and neuroprotection. The consequence of ROCK inhibition on ischemic rats' learning and spatial memory after 30 days of intracerebroventricular treatment was evaluated. It was found that Y27632 (ROCK inhibitor) reduced neurodegenerative markers, such as Fluoro-Jade, PHF (paired helicoidal filaments) immunoreactivity, and p25 protein levels, in the hippocampus of ischemic animals and improved learning and spatial memory tasks. However, Y27632 alone impaired sham animals' long-term memory. These findings demonstrated the beneficial impact of ROCK inhibition on tauopathy and altered p25 protein levels following global cerebral ischemia.
authors.affiliation: Neuroscience Group of Antioquia, Cellular and Molecular Neurobiology Area, School of Medicine, Sede de Investigacion Universitaria, University of Antioquia, Medellín, Colombia.
authors.forename: John Fredy
authors.initials: JF
authors.lastname: Castro-Alvarez
authors.forename: Johanna
authors.initials: J
authors.lastname: Gutierrez-Vargas
authors.forename: Muriel
authors.initials: M
authors.lastname: Darnaudéry
authors.forename: Gloria Patricia
authors.initials: GP
authors.lastname: Cardona-Gómez
mesh_terms: D000577:Amides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000523:psychology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D000577:Amides; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D011725:Pyridines; C103843:p25 protein (protein M subunit); D016875:tau Proteins; C108830:Y 27632; D051360:Cyclin-Dependent Kinase 5; D054460:rho-Associated Kinases