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Lipids

, Volume 46, Issue 5, pp 417–423 | Cite as

Long-Term Administration of Cod Liver Oil Ameliorates Cognitive Impairment Induced by Chronic Stress in Rats

  • Emil TrofimiukEmail author
  • Jan J. Braszko
Original Article

Abstract

Cod liver oil (CLO) is a rich source of omega-3 fatty acids (FA), especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The existing data suggest that EPA and DHA are the active agents of fish oil. In this study, we tested a hypothesis that the active constituents of CLO alleviate the negative impact of prolonged restraint stress on cognitive functions of male Wistar rats. Specifically, we attempted to characterize the preventive action of long-lasting treatment with CLO [0.375 ml/100 g body weight (equivalent to a dose of 300 mg/kg DHA and 225 mg/kg EPA), p.o. for 21 days] against an impairment caused by chronic restraint stress (2 h daily for 21 days) on recall as tested in a passive avoidance situation and on the spatial reference and working memory tested in a Barnes maze as well as on locomotor activity and anxiety behavior tested respectively in an open field and elevated plus-maze. We found that CLO administration statistically significantly (p < 0.01, both) prevented the deleterious effects of chronic restraint stress on recall and the spatial memory.

Keywords

Cod liver oil Stress Open field Elevated plus maze Passive avoidance Barnes maze Spatial memory 

Abbreviations

AD

Alzheimer’s disease

ANOVA

One-way analysis of variance

BDNF

Brain-derived neurotrophic factor

BM

Barnes maze

CLO

Cod liver oil

CaMKII

Ca(2+)/calmodulin-dependent protein kinase II

DHA

Docosahexaenoic acid

EPA

Eicosapentaenoic acid

FA

Omega-3 fatty acids

LTP

Long-term potentiation

mPFC

Medial prefrontal cortex

MWM

Morris water maze

NMDA

N-methyl-d-aspartate

PA

Passive avoidance

PUFA

Polyunsaturated fatty acids

SEM

Standard error of mean

Notes

Acknowledgments

This study was supported by the Medical University of Bialystok (3-66775L).

References

  1. 1.
    Ader R, Weijnen JAWM, Moleman P (1972) Retention of passive avoidance response as function of the intensity and duration of electric shock. Psychon Sci 26:125–129Google Scholar
  2. 2.
    Akbar M, Calderon F, Wen Z, Kim HY (2005) Docosahexaenoic acid: a positive modulator of Akt signaling in neuronal survival. Proc Natl Acad Sci USA 102:10858–10863PubMedCrossRefGoogle Scholar
  3. 3.
    Magariñs AM, McEwen BS (1995) Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: Comparison of stressors. Neuroscience 69(1):83–88PubMedCrossRefGoogle Scholar
  4. 4.
    Barnes CA (1979) Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comparat Physiol Psychol 1:74–104CrossRefGoogle Scholar
  5. 5.
    Bazan NG (2003) Synaptic lipid signaling: significance of polyunsaturated fatty acids and platelet-activating factor. J Lipid Res 44:2221–2233PubMedCrossRefGoogle Scholar
  6. 6.
    Braszko JJ, Wiśniewski K, Kupryszewski G, Witczuk B (1987) Psychotropic affects of angiotensin II and III in rats: locomotor and exploratory vs cognitive behaviour. Behav Brain Res 25:195–203PubMedCrossRefGoogle Scholar
  7. 7.
    Calon F, Lim GP, Yang F, Morihara T, Teter B, Ubeda O, Rostaing P, Triller A, Salem N Jr et al (2004) Docosahexaenoic acid protects from dendritic pathology in an Alzheimer’s disease mouse model. Neuron 43:633–645PubMedCrossRefGoogle Scholar
  8. 8.
    Chung WL, Chen JJ, Su HM (2008) Fish oil supplementation of control and (n-3) fatty acid-deficient male rats enhances reference and working memory performance and increases brain regional docosahexaenoic acid levels. J Nutr 138(6):1165–1171PubMedGoogle Scholar
  9. 9.
    Cook SC, Wellman CL (2004) Chronic stress alters dendritic morphology in rat medial prefrontal cortex. J Neurobiol 60:236–248PubMedCrossRefGoogle Scholar
  10. 10.
    Conrad CD. (2009) A critical review of chronic stress effects on spatial learning and memory. Prog Neuropsychopharmacol Biol Psychiatry. [Epub ahead of print]Google Scholar
  11. 11.
    Crawford MA, Golfetto I, Ghebremeskel K, Min Y, Moodley T, Poston L et al (2003) The potential role for arachidonic and docosahexaenoic acids in protection against some central nervous system injuries in preterm infants. Lipids 38:303–315PubMedCrossRefGoogle Scholar
  12. 12.
    Das UN (2006) Essential fatty acids: a review. Curr Pharm Biotechnol 7:467–482PubMedCrossRefGoogle Scholar
  13. 13.
    DeFilippis AP, Sperling LS (2006) Understanding omega-3’s. Am Heart J 151:564–570PubMedCrossRefGoogle Scholar
  14. 14.
    Delion S, Chalon S, Guilloteau D, Lejeune B, Besnard JC, Durand G (1997) Age-related changes in phospholipid fatty acid composition and monoaminergic neurotransmission in the hippocampus of rats fed a balanced or an n-3 polyunsaturated fatty acid-deficient diet. J Lipid Res 38:680–689PubMedGoogle Scholar
  15. 15.
    Elgersma Y, Sweatt JD, Giese KP (2004) Mouse genetic approaches to investigating calcium/calmodulin-dependent protein kinase II function in plasticity and cognition. J Neurosci 24:8410–8415PubMedCrossRefGoogle Scholar
  16. 16.
    Ferrari D, Cysneiros RM, Scorza CA, Arida RM, Cavalheiro EA, de Almeida AC, Scorza FA (2008) Neuroprotective activity of omega-3 fatty acids against epilepsy-induced hippocampal damage: Quantification with immunohistochemical for calcium-binding proteins. Epilepsy Behav 13(1):36–42PubMedCrossRefGoogle Scholar
  17. 17.
    Favrelere S, Stadelmann-Ingrand S, Huguet F, De Javel D, Piriou A, Tallineau C, Durand G (2000) Age-related changes in ethanolamine glycerophospholipid fatty acid levels in rat frontal cortex and hippocampus. Neurobiol Aging 21:653–660PubMedCrossRefGoogle Scholar
  18. 18.
    Fedorova I, Salem N Jr (2006) Omega-3 fatty acids and rodent behavior. Prostaglandins Leukot Essent Fatty Acids 75:271–289PubMedCrossRefGoogle Scholar
  19. 19.
    Gamoh S, Hashimoto M, Sugioka K, Shahdat Hossain M, Hata N, Misawa Y et al (1999) Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats. Neuroscience 93:237–241PubMedCrossRefGoogle Scholar
  20. 20.
    Goswami M, Mund S, Ray A (1996) Effects of some psychotropic agents on cognitive functions in rats. Indian J Physiol Pharmacol 40(1):75–78PubMedGoogle Scholar
  21. 21.
    Green P, Glozman S, Kamensky B, Yavin E (1999) Developmental changes in rat brain membrane lipids and fatty acids. The preferential prenatal accumulation of docosahexaenoic acid. J Lipid Res 40:960–966PubMedGoogle Scholar
  22. 22.
    Hashimoto M, Hossain S, Tanabe Y, Kawashima A, Harada T, Yano T, Mizuguchi K, Shido O (2009) The protective effect of dietary eicosapentaenoic acid against impairment of spatial cognition learning ability in rats infused with amyloid β(1–40). J Nutr Biochem 20(12): 965–973Google Scholar
  23. 23.
    Horrocks LA, Farooqui AA (2004) Docosahexaenoic acid in the diet: its importance in maintenance and restoration of neural membrane function. Prostaglandins Leukot Essent Fatty Acids 70:361–372PubMedCrossRefGoogle Scholar
  24. 24.
    Lim SY, Hoshiba J, Moriguchi T, Salem N Jr (2005) N-3 fatty acid deficiency induced by a modified artificial rearing method leads to poorer performance in spatial learning tasks. Pediatr Res 58:741–748PubMedCrossRefGoogle Scholar
  25. 25.
    Lim SY, Hoshiba J, Salem N Jr (2005) An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n-6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance. J Neurochem 95:848–857PubMedCrossRefGoogle Scholar
  26. 26.
    Martinez M (1992) Tissue levels of polyunsaturated fatty acids during early human development. J Pediatr 120:S129–S138PubMedCrossRefGoogle Scholar
  27. 27.
    Moriguchi T, Salem N Jr (2003) Recovery of brain docosahexaenoate leads to recovery of spatial task performance. J Neurochem 87:297–309PubMedCrossRefGoogle Scholar
  28. 28.
    Nishikawa M, Kimura S, Akaike N (1994) Facilitatory effect of docosahexaenoic acid on Nd-aspartate response in pyramidal neurons of rat cerebral cortex. J Physiol 475:83–93PubMedGoogle Scholar
  29. 29.
    Pellow S, File SE (1986) Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: a novel test of anxiety in the rat. Pharmacol Biochem Behav 24:525–529PubMedCrossRefGoogle Scholar
  30. 30.
    Prasad MR, Lovell MA, Yatin M, Dhillon H, Markesbery WR (1998) Regional membrane phospholipid alterations in Alzheimer’s disease. Neurochem Res 23:81–88PubMedCrossRefGoogle Scholar
  31. 31.
    Radley JJ, Sisti HM, Rocher AB, Hao J, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125:1–6PubMedCrossRefGoogle Scholar
  32. 32.
    Sastry PS (1985) Lipids of nervous tissue: composition and metabolism. Prog Lipid Res 24:69–176PubMedCrossRefGoogle Scholar
  33. 33.
    Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379PubMedCrossRefGoogle Scholar
  34. 34.
    Tanabe Y, Hashimoto M, Sugioka K, Maruyama M, Fujii Y, Hagiwara R et al (2004) Improvement of spatial cognition with dietary docosahexaenoic acid is associated with an increase in Fos expression in rat CA1 hippocampus. Clin Exp Pharmacol Physiol 31:700–703PubMedCrossRefGoogle Scholar
  35. 35.
    Tully AM, Roche HM, Doyle R, Fallon C, Bruce I, Lawlor B, Coakley D, Gibney MJ (2003) Low serum cholesteryl ester-docosahexaenoic acid levels in Alzheimer’s disease: a case-control study. Br J Nutr 89:483–489PubMedCrossRefGoogle Scholar
  36. 36.
    Vaynman S, Ying Z, Gomez-Pinilla F (2007) The select action of hippocampal calcium calmodulin protein kinase II in mediating exercise enhanced cognitive function. Neuroscience 144:825–833PubMedCrossRefGoogle Scholar
  37. 37.
    Wu A, Ying Z, Gomez-Pinilla F (2008) Docosahexaenoic acid dietary supplementation enhances the effects of exercise on synaptic plasticity and cognition. Neuroscience 155(3):751–759PubMedCrossRefGoogle Scholar
  38. 38.
    Yoshii A, Constantine-Paton M (2007) BDNF induces transport of PSD-95 to dendrites through PI3 K-AKT signaling after NMDA receptor activation. Nat Neurosci 10:702–711PubMedCrossRefGoogle Scholar

Copyright information

© AOCS 2011

Authors and Affiliations

  1. 1.Department of Clinical PharmacologyMedical University of BialystokBialystokPoland

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