Blood BDNF Concentrations Reflect Brain-Tissue BDNF Levels across Species
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) is involved in synaptic plasticity, neuronal differentiation and survival of neurons. Observations of decreased serum BDNF levels in patients with neuropsychiatric disorders have highlighted the potential of BDNF as a biomarker, but so far there have been no studies directly comparing blood BDNF levels to brain BDNF levels in different species. We examined blood, serum, plasma and brain-tissue BDNF levels in three different mammalian species: rat, pig, and mouse, using an ELISA method. As a control, we included an analysis of blood and brain tissue from conditional BDNF knockout mice and their wild-type littermates. Whereas BDNF could readily be measured in rat blood, plasma and brain tissue, it was undetectable in mouse blood. In pigs, whole-blood levels of BDNF could not be measured with a commercially available ELISA kit, but pig plasma BDNF levels (mean 994±186 pg/ml) were comparable to previously reported values in humans. We demonstrated positive correlations between whole-blood BDNF levels and hippocampal BDNF levels in rats (r2=0.44, p=0.025) and between plasma BDNF and hippocampal BDNF in pigs (r2=0.41, p=0.025). Moreover, we found a significant positive correlation between frontal cortex and hippocampal BDNF levels in mice (r2=0.81, p=0.0139). Our data support the view that measures of blood and plasma BDNF levels reflect brain-tissue BDNF levels.
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The correlation between peripheral and central BDNF is less clear in the frontal cortex, and in mice blood BDNF is undetectable despite measurable brain BDNF.
“However, this correlation is less clear in the frontal cortex, and significant species differences in BDNF transport and detection have been observed, particularly in mice, where blood BDNF is undetectable despite measurable brain BDNF levels [106].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [106]
The Discussion reports no significant frontal-cortex–blood BDNF correlation in rats or pigs, and reports undetectable blood BDNF despite detectable brain BDNF in mice. It supports species differences in detection, but does not establish the citing sentence’s claim of observed differences in transport; the Discussion says mice can transport labelled BDNF. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn rats and pigs, blood and plasma BDNF levels correlate with hippocampal BDNF levels, supporting peripheral BDNF as a biomarker for brain-derived BDNF.
“It has been demonstrated that in rats and pigs, BDNF levels in blood and plasma correlate with hippocampal BDNF levels, supporting the potential use of peripheral BDNF as a biomarker for brain-derived BDNF [106].”
From Variations in BDNF and Their Role in the Neurotrophic Antidepressant Mechanisms of Ketamine and Esketamine: A Review (2024) · cites this paper as [106]
Although the permeability of the blood-brain barrier for BDNF is very limited, there is evidence for a release of BDNF from the brain during exercise.
“Although the permeability of BBB for BDNF is very limited, there is evidence for a release of BDNF from the brain during exercise [174,175], which may reflect an association between peripheral and central BDNF levels and highlight plausibility of the hypothesis according to which the source of increased BDNF concentration due to exercise would be”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [175]
The release of BDNF from the brain during exercise may reflect an association between peripheral and central BDNF levels and highlight the plausibility of the hypothesis that the source of increased BDNF concentration due to exercise is the brain.
“Although the permeability of BBB for BDNF is very limited, there is evidence for a release of BDNF from the brain during exercise [174,175], which may reflect an association between peripheral and central BDNF levels and highlight plausibility of the hypothesis according to which the source of increased BDNF concentration due to exercise would be”
From BDNF as a Promising Therapeutic Agent in Parkinson’s Disease (2020) · cites this paper as [175]
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“Although never documented in humans, peripheral measures of BDNF appear to reflect brain tissue content well in other species (Klein et al., 2011).”
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- Authors
- Klein, A. B., Williamson, R., Santini, M. A., Clemmensen, C., Ettrup, A., Rios, M., Knudsen, G. M., & Aznar, S.
- Affiliations
- Copenhagen University Hospital (DK)
- Tufts University (US)
- Corresponding author
- Klein, Anders B.
- ORCID
- Venue
- The International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2010-07-07
- Volume
- 14
- Issue
- 03
- Pages
- 347-353
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- OpenAlex
- W2164147534
- Cited by
- 726
- References
- 25
- Citations by year
- 2026: 37 · 2025: 46 · 2024: 80 · 2023: 66 · 2022: 55 · 2021: 68 · 2020: 64 · 2019: 56 · 2018: 40 · 2017: 28 · 2016: 49 · 2015: 30 · 2014: 37 · 2013: 29 · 2012: 17
- FWCI
- 8.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Lundbeckfonden (R62-2010-5364, R90-2011-7722)
- Augustinus Fonden
- H. Lundbeck A/S
- National Institutes of Health
- National Institute of Mental Health (R01MH067817, MH67817)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK073311, DK073311)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- brain-derived neurotrophic factor, plasma BDNF, hippocampal BDNF, frontal cortex, BDNF knockout mice, cross-species comparison, rats, pigs, mice, biomarkers, serum BDNF
- MeSH terms
- Animals, Brain, Female, Frontal Lobe, Hippocampus, Male, Species Specificity, Swine, Reproducibility of Results, Mice, Knockout, Brain-Derived Neurotrophic Factor, Mice, Rats
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