Methylated Arginine Analogues: Their Potential Role in Atherosclerosis and Cognition Using the Poloxamer 407-induced Mouse Model of Dyslipidemia

An experimental mouse model of dyslipidemia and atherosclerosis was utilized to study the generation of methyarginines in vivo, as well as any potential behavioral changes in mice associated with the production of excess methylarginines. Following 14 weeks of poloxamer 407 treatment, mice developed atherosclerosis and the plasma concentrations of monomethylarginine and asymmetric dimethylarginine were found to be significantly greater than corresponding concentrations in control mice. This finding may have contributed to the development of aortic atherosclerotic lesions in poloxamer-treated mice by interfering with nitric oxide availability and hence, normal function of vascular endothelium. Poloxamer 407-treated mice also showed a significant decrease in locomotor and exploratory activity, together with signs of emotional stress and anxiety relative to controls. Passive/avoidance testing to assess learning and memory provided suggestive evidence that poloxamer-treated mice could potentially be characterized as having undergone a disruption in the process of forgetting about an aversive event; specifically, a foot shock, when compared to control mice. Thus, it is also suggested that the increase in both plasma monomethylarginine and asymmetric dimethylarginine in poloxamer-407-treated mice may somehow influence learning and memory, since endothelial dysfunction caused by reduced nitric oxide availability has been hypothesized to negatively influence cognitive function.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author