Circadian rhythm of brain-derived neurotrophic factor in serum and plasma

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments. What is the central question of this study? How does the circadian rhythm potentially influence peripheral brain-derived neurotrophic factor (BDNF) levels, and what has to be taken into consideration when interpretating BDNF levels in serum or plasma as potential biomarkers in neurodegenerative or psychiatric diseases? What is the main finding and its importance? Although plasma BDNF levels remain relatively stable over 24 h, serum BDNF exhibits a significant nocturnal decline, potentially linked to physical inactivity during sleep. Understanding this rhythm and the factors influencing BDNF levels is crucial for accurate interpretation of BDNF measurements, emphasizing the need to consider activity levels in standardized protocols for BDNF assessments.