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Published on: July 11, 2020
Robust changes in expression of brain-derived neurotrophic factor (BDNF) mRNA and protein across the brain do not
Thomas A Lanz1, Susan E Bove, Catherine D Pilsmaker
1Pfizer Global Research and Development, Groton, CT 06340, USA. thomas.a.lanz@pfizer.com
Abstract:
Adult rats were treated acutely with peripheral kainic acid (KA), and changes in brain-derived neurotrophic factor (BDNF) mRNA and protein were tracked over time across multiple brain regions. Despite robust elevation in both mRNA and protein in multiple brain regions, plasma BDNF was unchanged and cerebrospinal fluid (CSF) BDNF levels remained undetectable. Primary neurons were then treated with KA. BDNF was similarly elevated within neurons, but was undetectable in neuronal media. Thus, while deficits in BDNF signaling have been implicated in a number of diseases, these data suggest that extracellular concentrations of BDNF may not be a facile biomarker for changes in neurons.
Insights
Brain-derived neurotrophic factor (BDNF) increased in rat brains after kainic acid (KA) treatment, but remained undetectable in plasma and cerebrospinal fluid (CSF). This suggests extracellular BDNF is not a reliable biomarker for neuronal changes.
Area of Science:
- Neuroscience
- Molecular Biology
Background:
- Brain-derived neurotrophic factor (BDNF) is crucial for neuronal survival and function.
- Dysregulation of BDNF signaling is implicated in various neurological disorders.
Purpose of the Study:
- To investigate the relationship between neuronal BDNF levels and its extracellular concentrations in plasma and cerebrospinal fluid (CSF).
- To determine if extracellular BDNF can serve as a biomarker for changes in neuronal BDNF.
Main Methods:
- Adult rats were administered kainic acid (KA) to induce neuronal changes.
- BDNF mRNA and protein levels were measured in various brain regions over time.
- BDNF levels were also assessed in plasma, CSF, and neuronal cultures.
Main Results:
- KA treatment led to significant increases in both BDNF mRNA and protein within multiple brain regions.
- Plasma BDNF levels remained unchanged, and CSF BDNF levels were undetectable.
- In primary neuronal cultures, KA induced intracellular BDNF elevation but not in the surrounding media.
Conclusions:
- Intracellular BDNF levels increase in response to neuronal insult (KA).
- Extracellular BDNF concentrations in plasma and CSF do not reflect these intracellular changes.
- Extracellular BDNF is unlikely to be a reliable biomarker for monitoring neuronal BDNF status in conditions like those studied.
