Memory and Motor Coordination Improvement by Folic Acid Supplementation in Healthy Adult Male Rats

Document Type: Original Article


1 Department of Biology, Faculty of Sciences, Shahid Chamran University, Ahvaz, Iran

2 Department of Statistics, Faculty of Mathematic, Shahid Chamran University, Ahvaz, Iran


Previous studies have shown that vitamin B as well as folate supplementation has been implicated in cognitive and neurodegenerative disorders including Alzheimer’s and Parkinson's diseases. The aim of present study was to evaluate the effects of folic acid on passive avoidance task and motor coordination in healthy adult male rats.
Materials and Methods
Animals were randomly divided into five groups with 10 in each. 1) Sham treated (Veh); received same volume of normal saline as folate vehicle, 2-5) Test groups; each received a single dose of folate (5, 10 and 15 mg/ml/kg, IP daily for one week). At the end of the treatment with folic acid or vehicle, motor coordination in rotarod (after 24 hr) and passive avoidance memory in shuttle box (after 2 and 30 days) were evaluated, respectively.
The results showed that folic acid (5, 10, and 15 mg/kg) increased short-term (P<0.05, P<0.001) memory while, long term memory affected significantly with doses 10 and 15 mg/kg (P<0.01, P<0.001). On the other hand, folic acid (5 and 10 mg/kg) had significant improving effect on motor coordination (P<0.001, P<0.01) but with 15 mg/kg dose didn't have any effect on motor coordination.
Our results suggest that folic acid may improve both short- and long-term memories, dose dependently, although it affects motor balance at lower dose. The mechanism of folic acid effects on cognition and motor coordination is unknown and needs more investigations.


1. Mattson MP, Kruman II, Duan W. Folic acid and homocysteine in age-related disease. Aging Res Rev 2002; 1:95-111.

2. Meshkin B, Blum K. Folate nutrigenetics: A convergence of dietary folate metabolism, folic acid supplementation, and folate antagonist pharmacogenetics. Drug Metab Lett 2007; 1:55-60.

3. Brocardo PS, Budni J, Kaster MP, Santos AR, Rodriques AL. Folic acid administration produces an antidepressant-like effect in mice: Evidence for the involvement of the serotonergic and noradrenergic systems. Neuropharmacology 2008; 54:464-473.

4. Gregory S, Kelly ND. Folates: Supplemental forms and therapeutic application. Altern Med Rev 1998; 3:208-220.

5. Chen H, zhang SM, Schwarzschild MA, Hernan MA, Logroscino G, Willett WC, et al. Folate intake and risk of Parkinson's disease. Am J Epidemiol 2004; 160:368-375.

6. Durga J, Van Boxtel MP, Schouten EG, Bots ML, Kok HJ, Verhoef P. Folate and the methlenetetrahydrofolate reductase 677C→T mutation correlate with cognitive performance. Neurobiol Aging 2006; 27:334-343.

7. Lalonde R, Barraud H, Ravey J, Gueant JL, Bronowicki JP, Strazielle C. Effects of a B-vitamin-deficient diet on exploratory activity, motor coordination, and spatial learning in young adult Balb/c mice. Brain Res 2008; 1188:122-131.

8. Luchsinger JA, Tang MX, Miller J, Green R, Mayeux R. Relation of higher folate intake to lower risk of Alzheimer disease in the elderly. Arch Neurol 2007; 64:86-92.

9. Moretti A, Torre P, Antonello RM, Cattaruzza T, Cazzato G, Bava A. Vitamin B12 and folate depletion in cognition: A review. Neurol India 2004; 52:310-318.

10. Savaria Morris M, Jacques PF, Rosengerg IH, Selhub J. Folate and vitamin B12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Ame J Clin Nutr 2007; 85:193-200.

11. Das UN. Folic acid and polyunsaturated fatty acids improve cognitive function and prevent depression, dementia, and Alzheimer's disease-But how and why? Prostaglandins Leukot Essent Fatty Acids 2008; 78:11-19.

12. Tucker KL, Qiao N, Scott T, Rosenberg I, Spiro A. High homocysteine and low B vitaminsnpredict cognitive decline in aging men: the Veterans Affairs Normative Aging Study. Am Soc Clin Nutr 2005; 82:627-635.

13. Ramos MI, Allen LH, Mungas DM, Jaguest WJ, Haan MN, Green R, et al. Low folate status is associated with impairmed cognitive function and dementia in the Sacramento Area Latino Study on Aging. Am J Clin Nutr 2005; 82:1346-1352.

14. Troen AM, Chao WH, Crivello NA, E Danci K, Shukitt-hale B, Smith DE, et al. Cognitive impairment in folate-deficiency rats corresponds to depleted brain phosphatidylcholine and is prevented by dietary methionine without lowering plasma homocysteine. J Nutr 2008; 138:2502-2509.

15. Sachdev PS. Homocysteine and brain atrophy. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29:1152-1161.

16. Mattson MP, Shea TB. Folate and homocysteine metabolism in neuoral plasticity and neurodegenerative disorders. Trand Neurosci 2003; 26:137-146.

17. Martignoni E, Tassorelli C, Nappi G, Zangaglia R, Pacchetti C, Blandini F. Homocysteine and Parkinson's disease: A dangerous liaison? J Neurol Sci 2007; 257:31-37.

18. Pathansali R, Mangoni AA, Creaqh-Brown B, Lan ZC, Nqow GL, Yuan XF, et al. Effects of folic acid supplementation on psychomotor performance and hemorheology in healthy elderly subjects. Arch Gerontol Geriatr 2006; 43:127-137.

19. Duan W, Ladenheim B, Cutler RG, Kruman ll, Cadet JL, Mattson MP. Dietary folate deficiency and elevated homocysteine levels endanger dopaminergic neurons in models of Parkinson’s disease. J Neurochem 2002; 80:101–110.

20. Moazedi AA, Ehsani Vostacolaee S, Chinipardaz R. Effect of oral aluminum chloride administration during lactation on short and long-term memory of their offspring. Biol Sci 2008; 4:676-722.

21. Moazedi AA, khombi shooshtari M, Parham GA. Dose dependent effects of iron supplementation on short-term and long-term memory in adult male wistar rats. J Biol Sci 2010; 10:648-652.

22. Criswell HE, Breese GR. Similar effects of ethanol and flumazenil on acquisition of a shuttle-box avoidance response during withdrawal from chronic ethanol treatment. Br J Pharmacol 1993; 110:753-760.

23. Takeda A, T amanoH, Tochigi M. Zinc homeostasis in the hypocampus of zinc-dependent young adult rats. Neurochem Int 2005; 46:221-225.

24. Dekundy A, Pietraszek M, Schaefer D, Cenci MA, Danysz W. Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease. Brain Res Bull 2006; 14:18-26.

25. Gasbarri A, Pompili A, Pacitti C, Ciciraaa F. Comparative effects of lesions to the pnto-cerebellar and olivo-cerebellar pathways on motor and spatial learning in the rat. Neurosciense 2003; 116:1131–1140.

26. Seo HG, Dae_Yul K, park HW, Lee SU, Park SH. Early motor balance and coordination training increased synaptophysin in subcortical region of the ischemic rat brain. J Korean Med Sci 2010; 25:1638-1645.

27. Lollato G, Scarminio IS , Moreira EG. Behavioral effects of aqueous and dichloromethane extracts of erythrina speciosa Andrews, fabaceae, leaves in mic. Reva Bras Farmacogn 2010; 20:510-515

28. Reynold E. Vitamin B12 folic acid, and the nervous system. Lancet Neurol 2006; 5:949-960.

29. Tettamanti M, Garri MT, Nobili A, Riva E, Lucca U. Low folate and the risk of cognitive and functional deficits in the very old: The monzino 80-plus study. J Am Coll Nutr 2006; 25: 502-508.

30. Iskandar BJ, Nelson A, Resnick D, Dkene JH, Gao P, Jnson C, et al. Folic acid supplementation enhances repair of the adult nervous system. Ann Neurol 2004; 56:221-227.

31. De Lau LML, Refsum H, Smith AD, Johnston C, Breteler MM. Plasma folate concentration and cognitive performance: Rotterdam Scan Study. Am J Clin Nutr 2007; 86: 728-734.

32. Durga J, Van Boxtel MP, Schouten EG, Kok FJ, Katan MB, Verhoef P. Effect of 3-year folic acid supplementation on cognitive function in older adults in the FACIT trial: a randomized, Double blind, controlled trial. Lancet 2007; 369:208-216.

33. Ravaglia G, Forti P, Maioli F, Martelli M, Servadei L, Brunetti N, et al. Homocysteine and folate as risk factor for dementia and Alzheimer disease. Am J Clin Nutr 2005; 82:636-643.

34. Jacques PF, Bostom AG, Williams RR, Curtis Ellison R, Eckfeldt JH, Rosenberg IH, et al. Relation between folate status, a common mutation in methylenetetrahydrofolate reductase, and plasma homocysteine concentrations. Circulation 1996; 93:7–9.