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      Effects of YC-1 on Learning and Memory Functions of Aged Rats

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          Abstract

          Background

          The aim of this study was to investigate the effects of a potent nitric oxide-guanylate cyclase activator, 3-(5′-hydroxymethyl-2′-furyl)-1-benzylindazole (YC-1), on learning and memory functions in aged rats.

          Material/Methods

          Rats were divided into 2 groups as 4-month-old and 24-month-old rats. Rats received YC-1 (1 mg/kg/day) for 2 weeks long-term. Morris water maze (MWM) and passive avoidance (PA) tests were used to determine learning and memory functions.

          Results

          In the MWM test, there is a significant increase in the acquisition latency (1–4 days) of 24-month-old rats. There is a significant reduction in the “time spent in the escape platform’s quadrant” in 24-month-old rats compared to 4-month-old rats in the probe trial of the MWM test. YC-1 treatment reversed the reduction of the “time spent in the escape platform’s quadrant” of 24-month-old rats. In the PA test, there was no significant difference in the 1 st-day latency of rats in all groups. On the 2nd day, retention latency significantly decreased in the 24-month-old rats compared to 4-month-olds. YC-1 reversed the diminished retention latency in 24-month-old rats. YC-1 treatment and aging did not affect results of the locomotor activity test or the foot-shock sensitivity test, suggesting our results were not due to a change in motor activity or disability of the animals.

          Conclusions

          Our findings suggest that activation of the NO-sGC-cGMP pathway plays an important role in spatial and emotional learning and memory functions in aged rats.

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          Most cited references37

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          Place navigation impaired in rats with hippocampal lesions.

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            Molecular mechanisms of memory acquisition, consolidation and retrieval.

            Memory is often considered to be a process that has several stages, including acquisition, consolidation and retrieval. Memory can be modified further through reconsolidation and performance can change during extinction trials while the original memory remains intact. Recent studies of the molecular basis of these processes have found that many signaling molecules are involved in several stages of memory but, in some cases, molecular pathways may be selectively recruited only during certain stages of memory.
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              The significance of the cholinergic system in the brain during aging and in Alzheimer's disease.

              Acetylcholine is widely distributed in the nervous system and has been implicated to play a critical role in cerebral cortical development, cortical activity, controlling cerebral blood flow and sleep-wake cycle as well as in modulating cognitive performances and learning and memory processes. Cholinergic neurons of the basal forebrain complex have been described to undergo moderate degenerative changes during aging, resulting in cholinergic hypofunction that has been related to the progressing memory deficits with aging. Basal forebrain cholinergic cell loss is also a consistent feature of Alzheimer's disease, which has been suggested to cause, at least partly, the cognitive deficits observed, and has led to the formulation of the cholinergic hypotheses of geriatric memory dysfunction. Impaired cortical cholinergic neurotransmission may also contribute to beta-amyloid plaque pathology and increase phosphorylation of tau protein the main component of neurofibrillar tangles in Alzheimer's disease. Understanding the molecular mechanisms underlying the interrelationship between cortical cholinergic dysfunction, beta-amyloid formation and deposition, and tau pathology in Alzheimer's disease, would allow to derive potential treatment strategies to pharmacologically intervene in the disease-causing signaling cascade.
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                Author and article information

                Journal
                Med Sci Monit Basic Res
                Medical Science Monitor Basic Research
                Medical Science Monitor Basic Research
                International Scientific Literature, Inc.
                2325-4394
                2325-4416
                2014
                21 August 2014
                : 20
                : 130-137
                Affiliations
                [1 ]Department of Pharmacology, Medical Faculty and Experimental Medical Research and Application Center, Kocaeli University, Kocaeli, Turkey
                [2 ]Medical Faculty and Experimental Medical Research-Application Center, Kocaeli University, Kocaeli, Turkey
                [3 ]Department of Pharmacology and Psychopharmacology Research Unit, Faculty of Pharmacy, Marmara University, Istanbul, Turkey
                Author notes
                Corresponding Author: Ipek Komsuoglu Celikyurt, e-mail: ikcelikyurt@ 123456gmail.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                891064
                10.12659/MSMBR.891064
                4148360
                25144469
                cda839e1-a979-452e-ac55-df5854e0eeba
                © Med Sci Monit, 2014

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License

                History
                : 20 May 2014
                : 23 July 2014
                Categories
                Animal Studies

                avoidance learning,behavior,animal,guanylate cyclase,memory disorders,nitric oxide

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