Influence of Iron Deficiency on Memory and Learning in BALB/c Mice

Authors

Keywords:

iron; Morris water maze test; spatial learning; anemia; memory

Abstract

Introduction: Anemia is a global public health problem. Iron plays various roles in the human body, and the nervous system is one of the most affected by its deficiency.

Objective: To determine the influence of an iron-deficient diet and a normal diet for a mouse based on iron-related blood parameters on spatial memory and learning.

Methods: An experimental study was conducted with 48 male albino BALB/c mice less than one month old. These were randomly assigned to six groups with different diets and evaluation periods.

Results: Mice on iron-deficient diet showed a significant reduction in hemoglobin and serum iron levels, along with a lower performance in spatial memory and learning. However, those mice which were switched from an iron-deficient diet to a normal diet showed blood parameters and performance in spatial memory and learning similar to mice fed a normal diet.

Conclusions: Iron deficiency during growth can have negative effects on iron-related blood parameters and spatial memory and learning, but an early intervention with an appropriate diet can reverse these effects. Addressing dietary iron deficiency could be crucial to promote healthy cognitive development during growth.

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References

1. Khattar N, Triebswetter C, Kiely M, et al. Investigation of the association between cerebral iron content and myelin content in normative aging using quantitative magnetic resonance neuroimaging. NeuroImage. 2021;239:118267. DOI: 10.1016/j.neuroimage.2021.118267.

2. Vlasova RM, Wang Q, Willette A, et al. Infantile Iron Deficiency Affects Brain Development in Monkeys Even After Treatment of Anemia. Front Hum Neurosci. 2021;15:624107. DOI: 10.3389/fnhum.2021.624107.

3. Wu Q, Ren Q, Meng J, et al. Brain Iron Homeostasis and Mental Disorders. Antioxidants. 2023;12(11):1997. DOI: 10.3390/antiox12111997.

4. Levi S, Ripamonti M, Moro AS, et al. Iron imbalance in neurodegeneration. Mol Psychiatry. 2024;29(4):1139-52. DOI: 10.1038/s41380-023-02399-z.

5. Tang C, Yang J, Zhu C, et al. Iron metabolism disorder and multiple sclerosis: a comprehensive analysis. Front Immunol. 2024;15:1376838. DOI: 10.3389/fimmu.2024.1376838.

6. Porras CA, Rouault TA. Iron Homeostasis in the CNS: An Overview of the Pathological Consequences of Iron Metabolism Disruption. Int J Mol Sci. 2022;23(9):4490. DOI: 10.3390/ijms23094490.

7. Cheng R, Dhorajia VV, Kim J, et al. Mitochondrial iron metabolism and neurodegenerative diseases. Neurotoxicology. 2022;88:88-101. DOI: 10.1016/j.neuro.2021.11.003.

8. Antonides A, Schoonderwoerd AC, Scholz G, et al. Pre-weaning dietary iron deficiency impairs spatial learning and memory in the cognitive holeboard task in piglets. Front Behav Neurosci. 2015;9:291. DOI: 10.3389/fnbeh.2015.00291.

9. Baumgartner J, Smuts CM, Malan L, et al. Combined Deficiency of Iron and (n-3) Fatty Acids in Male Rats Disrupts Brain Monoamine Metabolism and Produces Greater Memory Deficits Than Iron Deficiency or (n-3) Fatty Acid Deficiency Alone. J Nutr. 2012;142(8):1463-71. DOI: 10.3945/jn.111.156281.

10. Carlson ES, Fretham SJB, Unger E, et al. Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems. J Neurodev Disord. 2010;2(3):133-43. DOI: 10.1007/s11689-010-9049-0.

11. Carlson ES, Tkac I, Magid R, et al. Iron Is Essential for Neuron Development and Memory Function in Mouse Hippocampus. J Nutr. 2009;139(4):672-9. DOI: 10.3945/jn.108.096354.

12. Hsieh HY, Chen YC, Hsu MH, et al. Maternal Iron Deficiency Programs Offspring Cognition and Its Relationship with Gastrointestinal Microbiota and Metabolites. Int J Environ Res Public Health. 2020;17(17):6070. DOI: 10.3390/ijerph17176070.

13. Rytych JL, Elmore MRP, Burton MD, et al. Early Life Iron Deficiency Impairs Spatial Cognition in Neonatal Piglets. J Nutr. 2012;142(11):2050-6. DOI: 10.3945/jn.112.165522.

14. Li Y, Li F, Qin D, et al. The role of brain derived neurotrophic factor in central nervous system. Front Aging Neurosci. 2022;14:986443. DOI: 10.3389/fnagi.2022.986443.

15. Berthou C, Iliou JP, Barba D. Iron, neuro-bioavailability and depression. eJHaem. 2021;3(1):263-75. DOI: 10.1002/jha2.321.

16. Pino JMV, Nishiduka ES, da Luz MHM, et al. Iron-deficient diet induces distinct protein profile related to energy metabolism in the striatum and hippocampus of adult rats. Nutr Neurosci. 2022;25(2):207-18. DOI: 10.1080/1028415X.2020.1740862.

17. Amaro-Terrazos JZ, Iparraguirre ME, Jiménez-Soria A. Efecto del consumo del extracto de quinua en anemia ferropénica inducida en ratones. Rev Salud Pública. 2019;21(2):232-5. DOI: 10.15446/rsap.v21n2.65311.

18. Gonzales-Carazas EF, Melgarejo-García GC, Chávez-Conde LK, et al. Efecto terapéutico del extracto etanólico de Erythroxylum coca spp. en anemia ferropénica inducida en ratas Holtzman macho. An Fac Med [Internet]. 2013 [citado 10/01/2025];74(1):7-10. Disponible en: https://www.redalyc.org/articulo.oa?id=37926449001

19. Aguirre Siancas EE. Influencia del tipo de masticación sobre la memoria y el aprendizaje espacial en ratones albinos de la cepa BALB/c. Neurología. 2017;32(4):236-40. DOI: 10.1016/j.nrl.2015.11.008.

20. Cubas-Mogollón JW, Jiménez-Sánchez SM, Ruiz-Ramírez E, et al. Effect of energy level of photobiomodulation therapy on bone repair in rats. Odovtos Int J Dent Sci. 2023;25(3):43-54. DOI: 10.15517/ijds.2023.54077.

21. Oyuela R, Lareo L, Muñoz L, et al. Efecto en el aprendizaje y la memoria espacial de un péptido sintético en ratas: estudio preliminar. Psicol Caribe [Internet]. 2004 [citado 10/01/2025];13:1-14. Disponible en: https://www.redalyc.org/articulo.oa?id=21301302

22. Isasi E, Figares M, Abudara V, et al. Gestational and Lactational Iron Deficiency Anemia Impairs Myelination and the Neurovascular Unit in Infant Rats. Mol Neurobiol. 2022;59(6):3738-54. DOI: 10.1007/s12035-022-02798-3

23. Zhang Q, Lu XM, Zhang M, et al. Adverse effects of iron deficiency anemia on pregnancy outcome and offspring development and intervention of three iron supplements. Sci Rep. 2021;11(1):1347. DOI: 10.1038/s41598-020-79971-y.

Published

2026-04-08

How to Cite

1.
Aguirre-Siancas EE, de-la-Cruz-Rodríguez R, Matuda-Silvestre JG, Lam-Figueroa NM. Influence of Iron Deficiency on Memory and Learning in BALB/c Mice. Rev Méd Electrón [Internet]. 2026 Apr. 8 [cited 2026 Apr. 13];48:e6426. Available from: https://revmedicaelectronica.sld.cu/index.php/rme/article/view/6426

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Section

Research article