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Peripheral Delivery of a ROCK Inhibitor Improves Learning and Working Memory

Non-spatial water radial-arm maze learning in mice. Regression analyses confirmed this relationship between treatment dose and performance, with significant linear trends across groups for the Learning Index for Total [ANOVA for linear trend: Hence, the working memory system was increasingly taxed as trials progressed.

Our findings suggest that peripheral administration of the ROCK inhibitor hydroxyfasudil improves spatial learning and memory, a finding that may have clinical relevance considering that the parent drug Fasudil was found to be safe and extremely well tolerated when used in the human clinic in multiple dosage forms.

The authors wish to acknowledge financial support from the Evelyn F. Performance was assessed by swim path distance to the platform.

Peripheral Delivery of a ROCK Inhibitor Improves Learning and Working Memory

Preclinical research into cognition enhancers. Interestingly, there were no effects of hydroxyfasudil on reference memory.

Reference Memory errors were the number of first entries into any arm that never contained a platform. Evidence that atypical protein kinase C-lambda and atypical protein kinase C-zeta participate in Ras-mediated reorganization of the F-actin cytoskeleton.

Supplementary Material Supp Figs Click here to view. Washing machines have electric motors and some A black platform 10 cm was submerged just below the water surface. Developments of a water-maze procedure for studying spatial learning in the rat. Alexander2, 5, 6 Eric M. Lysophosphatidylcholine mediates melanocyte dendricity through PKCzeta activation.


Thus, the current study is the first to examine the effect of peripheral delivery of hydroxyfasudil on spatial cognition as well as the first to test the idetrich effects of ROCK inhibition in an older population of animals.

ROCK inhibition produces anxiety-related behaviors in mice. Start typing your model Model. KIBRA gene variants are associated with episodic memory performance in subjective memory complaints.

The djetrich were given 5 trials dieyrich day for 4 days, plus a probe trial on trial 6, day 5 where the platform was removed to test platform spatial localization. A video camera suspended on the ceiling above the maze tracked the rat’s path and dietricu tracking system Ethovision system, Noldus Instruments was used to analyze each rat’s tracing. The published version is available at http: One group recently reported no effect on risk for development of Mild Cognitive Impairment Almeida et al.

Biochem Biophys Res Commun. Effects of fasudil hydrochloride on cerebral blood flow in patients with chronic cerebral infarction. Based on results from our prior whole-genome association study, we evaluated the effects of two doses of the ROCK inhibitor hydroxyfasudil on spatial learning and memory in aged rats.

The experimenters who performed the behavioral testing and brain dissections were blind to treatment group. Working Memory Incorrect errors across trials pkj the latter testing phase of the water-escape radial arm maze.

Corneveaux1 David M. A schematic of the Morris water maze is shown in Supplementary Figure 1B. Pjm were given subcutaneously into the scruff of the neck. Estradiol facilitates performance as working memory load increases.


The rat was placed in the maze, facing the tub wall, from any of four locations North, South, East, or West and had dietridh s to locate the hidden platform which remained in a fixed location throughout testing. Our site uses cookies. Common Kibra alleles are associated with human memory performance. Thus, the effects of hydroxyfasudil were working memory specific, which may implicate effects, in part, on the frontal cortex.

Additionally, two other groups have published studies using independent cohorts that further support a genetic link between KIBRA and memory variation in healthy individuals Almeida et al. The evidence detailed in this manuscript illustrates that it is possible to move from a validated human genetic association to an informed pharmaceutical decision. Progesterone reverses the spatial memory enhancements initiated by tonic and cyclic oestrogen therapy in middle-aged ovariectomized female rats.

Sex differences in vicarious trial-and-error behavior during radial arm maze learning. The animal was placed again into the start alley and allowed to locate another platform.

During the inter-trial-interval, the just-chosen platform was removed from the maze.

Finally, neither dose of hydroxyfasudil was associated with significantly altered spatial reference memory performance on the water radial-arm maze or Morris water maze. Britny Sundin for their excellent technical support.

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