Brain-derived Neurotrophic Factor in Megakaryocytes

Area of Science:

• Neuroscience
• Hematology
• Molecular Biology

Background:

• Brain-derived neurotrophic factor (BDNF) is crucial for neuronal function but expressed at low levels in neurons.
• BDNF is abundant in human platelets, making it a potential biomarker, yet its cellular origin in circulation is unclear.
• Previous assumptions linked serum BDNF levels to brain BDNF, but platelet origin remained uninvestigated.

Purpose of the Study:

• To determine the cellular origin of brain-derived neurotrophic factor (BDNF) found in human platelets.
• To investigate the expression and storage mechanisms of BDNF in megakaryocytes and platelets.
• To clarify the relationship between megakaryocyte/platelet BDNF and serum BDNF levels.

Main Methods:

• Primary megakaryocyte cultures were established from human and rat.
• BDNF gene expression in megakaryocytes was analyzed using transcript analysis.
• BDNF localization within megakaryocyte alpha-granules was examined, co-analyzing with platelet factor 4.
• BDNF expression was compared between human/rat and mouse megakaryocytes.

Main Results:

• Human and rat megakaryocytes express the BDNF gene, with transcript patterns similar to neurons.
• Specific stimuli (thapsigargin, external calcium) increased BDNF mRNA species for translation and detectable pro-BDNF.
• BDNF was localized in megakaryocyte alpha-granules, often co-stored with platelet factor 4.
• BDNF was undetectable in mouse megakaryocytes, correlating with its absence in mouse serum.

Conclusions:

• Megakaryocytes are the primary cellular source of BDNF found in human platelets.
• Platelets store and release BDNF from alpha-granules, influencing serum BDNF levels.
• Observed changes in serum BDNF in conditions like depression or exercise may reflect alterations in megakaryocyte/platelet BDNF dynamics, not solely brain BDNF levels.