Background: Magnesium (Mg) and manganese (Mn) play an important role in brain development and glutathione, the master antioxidant in the brain, is necessary for the cognitive function. This study is aimed at determining the effect of magnesium and manganese concentrations in hippocampus and prefrontal cortex on the glutathione function. The reduction in glutathione leads to memory impairment in -Y-maze in the isolation period. Methods: In this study, 16 male Sprague-Dawley rats were randomly divided into 2 groups: social and isolation. Based on previous studies, the isolation period was considered as 14 days, plus 1 week for acclimatization. On day 15, after assessing the memory with Y-maze, rats were examined for glutathione in serum, hippocampus, and prefrontal cortex. Also, serum, hippocampus, and prefrontal cortex were obtained for assessing Mn and Mg. Results: The memory in Y-maze was impaired in isolated rats. Also, glutathione in hippocampus and prefrontal cortex was reduced in isolated rats versus socialized rats. In serum assay, glutathione reduced in socialized rats versus isolated rats. Mg was reduced in isolated rats versus socialized rats in serum assay. Paradoxically, Mn was increased in isolated rats versus socialized rats in serum assay. In tissue assay, Mg in hippocampus increased in socialized rats versus isolated rats. Paradoxically, in prefrontal cortex Mg increased in isolated rats versus socialized rats. Mn in hippocampus showed increased concentration in socialized rats versus isolated rats. Paradoxically, Mn showed reduced concentration in prefrontal cortex in socialized rats versus isolated rats. Conclusion: Manganese and magnesium are necessary elements for maintaining enough level of cognition in the isolation period. Also, glutathione plays an important role.

Keywords:
Magnesium, Manganese, Glutathione, Isolation, Memory, Y-maze
1.
Takeda A, Ishiwatari S, Okada S: Manganese uptake into rat brain during development and aging. J Neurosci Res 1999; 56: 93–98.
2.
Bradbury MW, Crowder J, Desai S, Reynolds JM, Reynolds M, Saunders NR: Electrolytes and water in the brain and cerebrospinal fluid of the foetal sheep and guinea-pig. J Physiol 1972; 227: 591–610.
3.
Ratner MH, Fitzgerald E: Understanding of the role of manganese in parkinsonism and Parkinson disease. Neurology 2017; 88: 338–339.
4.
Kwakye GF, Paoliello M, Mukhopadhyay S, Bowman AB, Aschner M: Manganese-induced parkinsonism and Parkinson’s disease: shared and distinguishable features. Int J Environ Res Public Health 2015; 12: 7519–7540.
5.
Reaney SH, Bench G, Smith DR: Brain accumulation and toxicity of Mn (II) and Mn (III) exposures. Toxicol Sci 2006; 93: 114–124.
6.
Chang Y, Lee JJ, Seo JH, Song HJ, Kim JH, Bae SJ, Ahn JH, Park SJ, Jeong KS, Kwon YJ, Kim SH, Kim Y: Altered working memory process in the manganese-exposed brain. Neuroimage 2010; 53: 1279–1285.
7.
Eby GA, Eby KL: Rapid recovery from major depression using magnesium treatment. Medical Hypotheses 2006; 67: 362–370.
8.
Dean O, Bush AI, Berk M, Copolov DL, van den Buuse M: Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice. Behav Brain Res 2009; 198: 258–262.
9.
Pandya CD, Howell KR, Pillai A: Antioxidants as potential therapeutics for neuropsychiatric disorders. Neuropsychopharmacol Biol Psychiatry 2013; 46: 214–223.
10.
Preston AR, Eichenbaum H: Interplay of hippocampus and prefrontal cortex in memory. Curr Biol 2013; 23:R764–R773.
11.
Frankland PW, Bontempi B, Talton LE, Kaczmarek L, Silva AJ: The involvement of the anterior cingulate cortex in remote contextual fear memory. Science 2004; 304: 881–883.
12.
Yang MS, Wong MH: Changes in Ca, Cu, Fe, Mg, and Zn contents in mouse brain tissues after prolonged oral ingestion of brick tea liquor containing a high level of Al. Biol Trace Elem Res 2001; 80: 67–76.
13.
Mandillo S, Tucci V, Hölter SM, Meziane H, Banchaabouchi MA, Kallnik M, Lad HV, Nolan PM, Ouagazzal AM, Coghill EL, Gale K, Golini E, Jacquot S, Krezel W, Parker A, Riet F, Schneider I, Marazziti D, Auwerx J, Brown SD, Chambon P, Rosenthal N, Tocchini-Valentini G, Wurst W: Reliability, robustness, and reproducibility in mouse behavioral phenotyping: a cross-laboratory study. Physiol Genomics 2008; 34: 243–255.
14.
Cefaratti C, Romani AM: Functional characterization of two distinct Mg2+ extrusion mechanisms in cardiac sarcolemmal vesicles. Mol Cell Biochem 2007; 303: 63–72.
15.
Sotogaku N, Oku N, Takeda A: Manganese concentration in mouse brain after intravenous injection. J Neurosci Res 2000; 6: 350–356.
16.
Philbert MA, Beiswanger CM, Waters DK, Reuhl KR, Lowndes H: Cellular and regional distribution of reduced glutathione in the nervous system of the rat: histochemical localization by mercury orange and o-phthaldialdehyde-induced histofluorescence. Toxicol Appl Pharmacol 1991; 107: 215–227.
17.
Keelan J, Allen NJ, Antcliffe D, Pal S, Duchen MR: Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane. J Neurosci Res 2001; 66: 873–884.
18.
Michels L, Schulte-Vels T, Schick M, O'Gorman RL, Zeffiro T, Hasler G, Mueller-Pfeiffer C: Prefrontal GABA and glutathione imbalance in posttraumatic stress disorder: preliminary findings. Psychiatry Res 2014; 224: 288–295.
19.
Pocernich CB, Butterfield DA: Elevation of glutathione as a therapeutic strategy in Alzheimer disease. Biochim Biophys Acta 2012; 1822: 625–630.
20.
Famitafreshi H, Karimian M, Fanaei H, Attari F, Fatima S: Social isolation is associated with reduced neurogenesis, impaired spatial working memory performance and altered anxiety levels in male rats. Open Access Anim Physiol 2015; 7: 87–95.
21.
Yavuz Y, Mollaoglu H, Yürümez Y, Ucok K, Duran L, Tünay K, Akgün L: Therapeutic effect of magnesium sulphate on carbon monoxide toxicity-mediated brain lipid peroxidation. Eur Rev Med Pharmacol Sci 2013; 17(suppl 1): 28–33.
© 2018 S. Karger AG, Basel
2018
Copyright / Drug Dosage / Disclaimer
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.
You do not currently have access to this content.