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      Dose-Response Effect of Egg-Phosphatidylcholine on Maze-Learning Ability and Fatty Acid Composition of Plasma and Brain in Aged Mice Fed an n–3 Fatty Acid-Deficient Diet

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          Abstract

          Background/Aims: We investigated the dose-response effect of egg-phosphatidylcholine (PC) on the maze-learning ability and brain fatty acid composition in aged mice. Method: Male Crj:CD-1 mice aged 18 months were fed the following diets for 4 months: (i) 5 g palm oil/100 g diet (n–3-deficient control group); (ii) 1 g egg-PC/100 g diet plus 4 g palm oil/100 g diet (egg-PC 1% group); (iii) 2.5 g egg-PC/100 g diet plus 2.5 g palm oil/100 g diet (egg-PC 2.5% group), and (iv) 5 g egg-PC/100 g diet (egg-PC 5% group). Maze-learning ability was assessed 3 months after the start of the experiment. All animals were maintained on the n–3 fatty acid-deficient diets to examine the direct effect of egg-PC on maze behavior. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in 3 trials every 4 days. Results: Our results showed that the 2.5 and 5% egg-PC groups needed less (p < 0.05) time to find the exit and strayed into blind alleys fewer times (p < 0.05) than the control group. In order to determine the relationship between maze-behavior and brain docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in aged mice fed various doses of egg-PC, the plasma and brain fatty acid composition was examined. Dose-response increases in the percentage of DHA were found in plasma lipids. However, based on our data on the brain fatty acid composition of mice fed various doses of egg-PC, no significant differences in the percentages of DHA and AA among the dietary groups were observed. Conclusion: These results suggest that the intake of egg-PC improves maze-learning ability in aged mice fed n–3 fatty acid-deficient diets but it does not influence the percentage of brain DHA and AA.

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          Behavioral deficits associated with dietary induction of decreased brain docosahexaenoic acid concentration.

          Docosahexaenoic acid (DHA), an n-3 fatty acid, is rapidly deposited during the period of rapid brain development. The influence of n-3 fatty acid deficiency on learning performance in adult rats over two generations was investigated. Rats were fed either an n-3 fatty acid-adequate (n-3 Adq) or -deficient (n-3 Def) diet for three generations (F1-F3). Levels of total brain n-3 fatty acids were reduced in the n-3 Def group by 83 and 87% in the F2 and F3 generations, respectively. In the Morris water maze, the n-3 Def group showed a longer escape latency and delayed acquisition of this task compared with the n-3 Adq group in both generations. The acquisition and memory levels of the n-3 Def group in the F3 generation seemed to be lower than that of the F2 generation. The 22:5n-6/22:6n-3 ratio in the frontal cortex and dams' milk was markedly increased in the n-3 Def group, and this ratio was significantly higher in the F3 generation compared with the F2 generation. These results suggest that learning and cognitive behavior are related to brain DHA status, which, in turn, is related to the levels of the milk/dietary n-3 fatty acids.
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            Treatment of cognitive dysfunction associated with Alzheimer's disease with cholinergic precursors. Ineffective treatments or inappropriate approaches?

            The observations of the loss of cholinergic function in neocortex and hippocampus in Alzheimer's disease (AD) developed the hypothesis that replacement of cholinergic function may be of therapeutic benefit to AD patients. The different approaches proposed or tested included intervention with acetylcholine (ACh) precursors, stimulation of ACh release, use of muscarinic or nicotinic receptor agonists and acetylcholinesterase (AChE) or cholinesterase (ChE) inhibition. Inhibition of endogenous ACh degradation through ChE inhibitors and precursor loading were treatments more largely investigated in clinical trials. Of the numerous compounds in development for the treatment of AD, AChE and ChE inhibitors are the most clinically advanced, although clinical trials conducted to date did not always confirm a significant benefit of these drugs on all symptom domains of AD. The first attempts in the treatment of AD with cholinergic precursors did not confirm a clinical utility of this class of compounds in well controlled clinical trials. However, cholinergic precursors most largely used such as choline and phosphatidylcholine (lecithin) were probably not suitable for enhancing brain levels of ACh. Other phospholipids involved in choline biosynthetic pathways such as CDP-choline, choline alphoscerate and phosphatidylserine clearly enhanced ACh availability or release and provided a modest improvement of cognitive dysfunction in AD, these effects being more pronounced with choline alphoscerate. Although some positive results cannot be generalized due to the small numbers of patients studied, they probably would justify reconsideration of the most promising molecules in larger carefully controlled trials.
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              Hypertrophy of basal forebrain neurons and enhanced visuospatial memory in perinatally choline-supplemented rats.

              The effects of choline supplementation during two time-frames of early development on radial-arm maze performance and the morphology of basal forebrain neurons immunoreactive for the P75 neurotrophin receptor (NTR) in male and female Sprague-Dawley rats were examined. In the first experiment, rats were supplemented with choline chloride from conception until weaning. At 80 days of age, subjects were trained once a day on a 12-arm radial maze for 30 days. Compared to control littermates, supplemented rats made fewer working and reference memory errors; however, the memory enhancing effects of choline supplementation were greater in males than females. A morphometric analysis of NTR-immunoreactive cell bodies at three levels through the medial septum/diagonal band (MS/DBv) of these rats revealed that perinatal choline supplementation caused the somata of cells in the MS/DBv to be larger by 8-15%. In a second experiment, choline supplementation was restricted to embryonic days 12-17. A developmental profile of NTR immunoreactive cell bodies in the MS/DBv of 0-, 8-, 16-, 30- and 90-day old male and female rats again revealed that cell bodies were larger in choline-supplemented rats than controls. As in the behavioral studies, the effect of choline supplementation was greater in male than female rats. These data are consistent with the hypothesis that supplementation with choline chloride during early development leads to an increase in the size of cell bodies of NTR-immunoreactive cells in the basal forebrain and that this change may contribute to long-term improvement in spatial memory. Copyright 1998 Elsevier Science B.V. All rights reserved.
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                Author and article information

                Journal
                ANM
                Ann Nutr Metab
                10.1159/issn.0250-6807
                Annals of Nutrition and Metabolism
                S. Karger AG
                0250-6807
                1421-9697
                2002
                October 2002
                09 October 2002
                : 46
                : 5
                : 215-221
                Affiliations
                National Food Research Institute, Tsukuba, Ibaraki, Japan
                Article
                65410 Ann Nutr Metab 2002;46:215–221
                10.1159/000065410
                12378046
                3880e008-91ac-49d1-a678-ab02f37cefa0
                © 2002 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 18 July 2001
                : 20 April 2002
                Page count
                Figures: 2, Tables: 4, References: 30, Pages: 7
                Categories
                Original Paper

                Nutrition & Dietetics,Health & Social care,Public health
                Maze-learning ability,Dose-response,Brain fatty acids,Polyunsaturated fatty acids,Phosphatidylcholine

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