Skip to main content
SpringerLink
Log in

Effect of BDNF Val66Met Polymorphism on Digital Working Memory and Spatial Localization in a Healthy Chinese Han Population

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Cognitive abilities are complex human traits influenced by genetic factors. Brain-derived neurotrophic factor (BDNF), a unique polypeptide growth factor, has an influence on the differentiation and survival of neurons in the nervous system. A single-nucleotide polymorphism (rs6265) in the human gene, resulting in a valine to methionine substitution in the pro-BDNF protein, was thought to associate with psychiatric disorders and might play roles in the individual difference of cognitive abilities. However, the specific roles of the gene in cognition remain unclear. To investigate the relationships between the substitution and cognitive abilities, a healthy population-based study and the PCR-SSCP method were performed. The results showed the substitution was associated with digital working memory (p = 0.02) and spatial localization (p = 0.03), but not with inhibition, shifting, updating, visuo-spatial working memory, long-term memory, and others (p > 0.05) among the compared genotype groups analyzed by general linear model. On the other hand, the participants with BDNF GG had higher average performance in digital working memory and spatial localization than the ones with BDNF AA. The findings of the present work implied that the variation in BDNF might play positive roles in human digital working memory and spatial localization.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Plomin, R., & Kosslyn, S. M. (2001). Genes, brain and cognition. Nature Neuroscience, 4, 1153–1154. doi:10.1038/nn1201-1153.

    Article  PubMed  CAS  Google Scholar 

  • Houlihan, L. M., Harris, S. E., et al. (2009). Replication study of candidate genes for cognitive abilities: The Lothian birth cohort 1936. Genes Brain Behav, 8, 238–247.

    Article  PubMed  CAS  Google Scholar 

  • Egan, M. F., Straub, R. E., et al. (2004). Variation in Grm3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proceedings of the National Academy of Sciences of the United States of America, 101, 12604–12609. doi:10.1073/pnas.0405077101.

    Article  PubMed  CAS  Google Scholar 

  • Tan, H. Y., Chen, Q., et al. (2007). Epistasis between catechol-o-methyltransferase and type Ii metabotropic glutamate receptor 3 genes on working memory brain function. Proceedings of the National Academy of Sciences of the United States of America, 104, 12536–12541. doi:10.1073/pnas.0610125104.

    Article  PubMed  CAS  Google Scholar 

  • Hanson, I. M., Seawright, A., et al. (1992). The human Bdnf gene maps between Fshb and Hvbs1 at the boundary of 11p13–P14. Genomics, 13, 1331–1333. doi:10.1016/0888-7543(92)90060-6.

    Article  PubMed  CAS  Google Scholar 

  • Easton, J. B., Moody, N. M., et al. (1999). Brain-derived neurotrophic factor induces phosphorylation of fibroblast growth factor receptor substrate 2. The Journal of Biological Chemistry, 274, 11321–11327. doi:10.1074/jbc.274.16.11321.

    Article  PubMed  CAS  Google Scholar 

  • Wang, Z. L., Mao, M., et al. (2007). Signaling pathway of Bdnf protecting embryonic cortical neurons from hypoxia. Sichuan Da Xue Xue Bao Yi Xue Ban, 38, 934–937.

    PubMed  CAS  Google Scholar 

  • Zhou, J., Bradford, H. F., et al. (1996). Induction of dopaminergic neurotransmitter phenotype in rat embryonic cerebrocortex by the synergistic action of neurotrophins and dopamine. The European Journal of Neuroscience, 8, 2328–2339. doi:10.1111/j.1460-9568.1996.tb01196.x.

    Article  PubMed  CAS  Google Scholar 

  • Hwang, I. K., Yoo, K. Y., et al. (2006). Correlations between neuronal loss, decrease of memory, and decrease expression of brain-derived neurotrophic factor in the gerbil hippocampus during normal aging. Experimental Neurology, 201, 75–83. doi:10.1016/j.expneurol.2006.02.129.

    Article  PubMed  CAS  Google Scholar 

  • Bimonte-Nelson, H. A., Singleton, R. S., et al. (2003). Testosterone, but not nonaromatizable dihydrotestosterone, improves working memory and alters nerve growth factor levels in aged male rats. Experimental Neurology, 181, 301–312. doi:10.1016/S0014-4886(03)00061-X.

    Article  PubMed  CAS  Google Scholar 

  • Costa, M. S., Botton, P. H., et al. (2008). Caffeine prevents age-associated recognition memory decline and changes brain-derived neurotrophic factor and tirosine kinase receptor (Trkb) content in mice. Neuroscience, 153, 1071–1078. doi:10.1016/j.neuroscience.2008.03.038.

    Article  PubMed  CAS  Google Scholar 

  • Harris, S. E., Fox, H., et al. (2006). The brain-derived neurotrophic factor Val66met polymorphism is associated with age-related change in reasoning skills. Molecular Psychiatry, 11, 505–513. doi:10.1038/sj.mp. 4001799.

    Article  PubMed  CAS  Google Scholar 

  • Oroszi, G., Lapteva, L., et al. (2006). The Met66 allele of the functional Val66met polymorphism in the brain-derived neurotrophic factor gene confers protection against neurocognitive dysfunction in systemic lupus erythematosus. Annals of the Rheumatic Diseases, 65, 1330–1335. doi:10.1136/ard.2006.051623.

    Article  PubMed  CAS  Google Scholar 

  • Lu, B., & Martinowich, K. (2008). Cell biology of Bdnf and its relevance to schizophrenia. Novartis Foundation Symposium, 289, 119–129. discussion 129–135, 193–115.

    Article  PubMed  CAS  Google Scholar 

  • Kapczinski, F., Frey, B. N., et al. (2008). Brain-derived neurotrophic factor and neuroplasticity in bipolar disorder. Expert Review of Neurotherapeutics, 8, 1101–1113. doi:10.1586/14737175.8.7.1101.

    Article  PubMed  CAS  Google Scholar 

  • Goldberg, T. E., Iudicello, J., et al. (2008). Bdnf Val66met polymorphism significantly affects D' in verbal recognition memory at short and long delays. Biological Psychology, 77, 20–24. doi:10.1016/j.biopsycho.2007.08.009.

    Article  PubMed  Google Scholar 

  • Szekeres, G., Juhasz, A., et al. (2003). The C270t polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia. Schizophrenia Research, 65, 15–18. doi:10.1016/S0920-9964(02)00505-4.

    Article  PubMed  Google Scholar 

  • Xu, X., Mill, J., Zhou, K., Brookes, K., Chen, C. K., & Asherson, P. (2007). Family-based association study between brain-derived neurotrophic factor gene polymorphisms and attention deficit hyperactivity disorder in UK and Taiwanese samples. American Journal of Medical Genetics. Part B, Neuropsychiatric genetics: The Official Publication of the International Society of Psychiatric Genetics, 144B, 83–86. doi:10.1002/ajmg.b.30406.

    CAS  Google Scholar 

  • Hegarty, M., Shah, P., et al. (2000). Constraints on using the dual-task methodology to specify the degree of central executive involvement in cognitive tasks. Memory & Cognition, 28, 376–385.

    CAS  Google Scholar 

  • Kane, M. J., Conway, A. R., Miura, T. K., & Colflesh, G. J. (2007). Working memory, attention control, and the N-back task: A question of construct validity. Journal of Experimental Psychology. Learning, Memory, and Cognition, 33, 615–622. doi:10.1037/0278-7393.33.3.615.

    Article  PubMed  Google Scholar 

  • Nieuwenhuis, S., Ridderinkhof, K. R., de Jong, R., Kok, A., & van der Molen, M. W. (2000). Inhibitory inefficiency and failures of intention activation: Age-related decline in the control of saccadic eye movements. Psychology and aging, 15(4), 635–47. doi:10.1037/0882-7974.15.4.635.

    Article  PubMed  CAS  Google Scholar 

  • Miyake, A., Friedman, N. P., et al. (2000). The unity and diversity of executive functions and their contributions to complex “frontal lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49–100. doi:10.1006/cogp.1999.0734.

    Article  PubMed  CAS  Google Scholar 

  • Deming Li, C. L., & Li, G. (2001). The construction of “basic cognitive capacity test” and it's standardization. Journal of Chinese Psychology Acta Psychologica Sinica, 5, 453–460.

    Google Scholar 

  • Gordon, H. W. (1986). The cognitive laterality battery: Tests of specialized cognitive function. The International Journal of Neuroscience, 29, 223–244.

    Article  PubMed  CAS  Google Scholar 

  • Xufeng Liu, F. H., Miao, D., Qi, J., Wang, W., Liu, L., & Chao, Y. (2004). Relationship between spatial ability and variables of mental rotation. Chinese Journal of Behavioral Medical Science, 13, 55–56.

    Google Scholar 

  • Margolin, D. I., Pate, D. S., et al. (1990). Dysnomia in dementia and in stroke patients: Different underlying cognitive deficits. Journal of Clinical and Experimental Neuropsychology, 12, 597–612. doi:10.1080/01688639008401004.

    Article  PubMed  CAS  Google Scholar 

  • Loonstra, A. S., Tarlow, A. R., et al. (2001). Cowat metanorms across age, education, and gender. Applied Neuropsychology, 8, 161–166. doi:10.1207/S15324826AN0803_5.

    Article  PubMed  CAS  Google Scholar 

  • Clark, H. H., & Chase, W. G. (1972). On the process of comparing sentences against pictures. Cognitive Psychology, 3, 472–517. doi:10.1016/0010-0285(72)90019-9.

    Article  Google Scholar 

  • Kunugi, H., Ueki, A., et al. (2001). A novel polymorphism of the brain-derived neurotrophic factor (Bdnf) gene associated with late-onset Alzheimer's disease. Molecular Psychiatry, 6, 83–86. doi:10.1038/sj.mp. 4000792.

    Article  PubMed  CAS  Google Scholar 

  • Egan, M. F., Kojima, M., et al. (2003). The Bdnf Val66met polymorphism affects activity-dependent secretion of Bdnf and human memory and hippocampal function. Cell, 112, 257–269. doi:10.1016/S0092-8674(03)00035-7.

    Article  PubMed  CAS  Google Scholar 

  • Yu, H., Zhang, Z., et al. (2008). Association study of the decreased serum Bdnf concentrations in amnestic mild cognitive impairment and the Val66met polymorphism in Chinese Han. The Journal of Clinical Psychiatry, 69, 1104–1111.

    Article  PubMed  CAS  Google Scholar 

  • Huang, R., Huang, J., et al. (2007). Genetic variants in brain-derived neurotrophic factor associated with Alzheimer's disease. Journal of Medical Genetics, 44, e66. doi:10.1136/jmg.2006.044883.

    Article  PubMed  CAS  Google Scholar 

  • Rybakowski, J. K., Borkowska, A., et al. (2006). Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66met polymorphism of the brain-derived neurotrophic factor gene. Psychiatry and Clinical Neurosciences, 60, 70–76. doi:10.1111/j.1440-1819.2006.01462.x.

    Article  PubMed  CAS  Google Scholar 

  • Miyajima, F., Ollier, W., et al. (2008). Brain-derived neurotrophic factor polymorphism Val66met influences cognitive abilities in the elderly. Genes Brain & Behavior, 7, 411–417. doi:10.1111/j.1601-183X.2007.00363.x.

    Article  CAS  Google Scholar 

  • Li, Y. J., Peng, S. L., Wan, C. Q., Cao, L., & Li, Y. P. (2005). Chronic pain impairs spatial learning and memory ability and down-regulates Bcl-2 and Bdnf Mrna expression in hippocampus of neonatal rats. Chinese Journal of Pediatrics, 43, 444–448.

    PubMed  Google Scholar 

  • Francia, N., Cirulli, F., et al. (2006). Spatial memory deficits in middle-aged mice correlate with lower exploratory activity and a subordinate status: Role of hippocampal neurotrophins. The European Journal of Neuroscience, 23, 711–728. doi:10.1111/j.1460-9568.2006.04585.x.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We sincerely thank all the participants and researchers in this study. This work was supported by the Special Prophase Project on Basic Research of The National Department of Science and Technology (2007CB516702).

Author information

Authors and Affiliations

  1. Key Laboratory of Resource Biology and Biotechnology in Western China (Ministry of Education), Institute of Population & Health, College of Life Science, Northwest University, Xi’an, China

    Pingyuan Gong, Anyun Zheng, Dongmei Chen, Wanhua Ge, Changchao Lv, Kejin Zhang, Xiaocai Gao & Fuchang Zhang

  2. Institute of Application Psychology, College of Public Management, Northwest University, Xi’an, China

    Anyun Zheng, Wanhua Ge, Changchao Lv, Xiaocai Gao & Fuchang Zhang

  3. School of Life Science, Northwest University, 229 Tai Bai Road, Xi’an, 710069, China

    Fuchang Zhang

Authors
  1. Pingyuan Gong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anyun Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dongmei Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wanhua Ge
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changchao Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kejin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiaocai Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fuchang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fuchang Zhang.

Additional information

Pingyuan Gong and Anyun Zheng contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gong, P., Zheng, A., Chen, D. et al. Effect of BDNF Val66Met Polymorphism on Digital Working Memory and Spatial Localization in a Healthy Chinese Han Population. J Mol Neurosci 38, 250–256 (2009). https://doi.org/10.1007/s12031-009-9205-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-009-9205-8

Keywords

Search

Navigation