Age-modulated association between prefrontal NAA and the BDNF gene
DOKPE
- Salehi, Basira University of Bern, Switzerland
- Preuss, Nora University of Bern, Switzerland
- van der Veen, Jan Willem National Institute of Mental Health, Bethesda, MD, US
- Shen, Jun National Institute of Mental Health, Bethesda, MD, US
- Neumeister, Alexander Yale School of Medicine, New York, US
- Drevets, Wayne C. The University of Oklahoma-College of Medicine, Tulsa, US
- Hodgkinson, Colin National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD, US
- Goldman, David National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, MD, US
- Wendland, Jens R. National Institute of Mental Health, Bethesda, MD, US
- Singleton, Andrew National Institute on Aging, Bethesda, MD, US
- Gibbs, J. Raphael National Institute on Aging, Bethesda, MD, US
- Cookson, Mark R. National Institute on Aging, Bethesda, MD, US
- Hasler, Gregor ORCID University of Bern, Switzerland
- 2013
Published in:
- International Journal of Neuropsychopharmacology. - Oxford UK : Oxford University Press (OUP). - 2013, vol. 16, no. 6, p. 1185-1193
Pharmacology (medical)
Psychiatry and Mental health
Pharmacology
BDNF
N-acetyl-aspartate
proton magnetic resonance spectroscopy
SNP
genetic variation
English
Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of Nacetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p=0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant interaction between rs1519480 and age on NAA level (p=0.031) Specifically, the effect of rs1519480 on NAA level became significant at age ≥ 34.17. NAA level decreased with advancing age for genotype TT (p=0.001) but not for genotype CT (p=0.82) or CC (p=0.34). Additional in silico analysis of 142 postmortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to interindividual variation in cognitive performance seen during normal aging, as well as contributing to the risk for developing psychiatric and neurological conditions.
- Faculty
- Faculté des sciences et de médecine
- Department
- Master en médecine
- Language
-
- English
- Classification
- Pathology, clinical medicine
- License
- Rights reserved
- Open access status
- green
- Identifiers
-
- DOI 10.1017/S1461145712001204
- ISSN 1469-5111
- ISSN 1461-1457
- Persistent URL
- https://folia.unifr.ch/unifr/documents/327983
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