Abstract Number: PB0376
Meeting: ISTH 2022 Congress
Background: The Brain-Derived Neurotrophic Factor (BDNF) promotes neuronal growth and survival, acting through alternatively spliced isoforms of the full length TrkB receptor and the 75 kDa pan-neurotrophic receptor (p75NTR). TrkB and p75NTR receptors cross-regulate each other’s signal and ligand bindings. BDNF is present in brain and serum, and platelets can have 1000-fold greater BDNF than neurons. We have shown that washed platelets aggregate in response to BDNF via the activation of a truncated TrkB receptor. Whether p75NTR is present in platelets and regulates BDNF-induced platelet aggregation remains unknown.
Aims: To characterize p75NTR expression and function in platelets.
Methods: Washed platelets were prepared from whole blood of healthy male and female volunteers. p75NTR expression was assessed by immunoblotting, flow cytometry and confocal microscopy, and quantified by ELISA (n=20). Platelets were activated using classical agonists (ADP, collagen, thrombin receptor activating peptide [TRAP]) and BDNF, in the presence of p75NTR inhibitor THX-B or negative control inactive analog, THX. Aggregation was measured by light transmission aggregometry. Signaling pathways downstream of BDNF activation were assessed by anti-phosphoprotein immunoblot.
Results: p75NTR immunoreactivity was detected on the surface of (28.3±19.4%) and within (56.4±18.4%) platelets. p75NTR levels quantified by ELISA were highly variable, with a 10-fold difference between highest (382 pg/ml) and lowest values (38 pg/ml), and did not change following platelet activation. Collagen-, ADP-, and TRAP-induced aggregation were not affected by the p75NTR inhibitor, THX-B. Inhibition of BDNF-induced platelet aggregation showed high interindividual variation (32.4±36.8% inhibition): THX-B-induced responses ranged from no effect in 50%, partial effect in 30% to a complete abrogation of platelet aggregation in 20% of participants.
Conclusion(s): Pharmacological inhibition of p75NTR abrogated BDNF-induced platelet aggregation in some but not all healthy volunteers. Whether this variability in aggregation is related to the high interindividual variation in platelet p75NTR levels remains to be established.
To cite this abstract in AMA style:
Fleury S, Boukhatem I, Welman M, Maurand É, Allen B, Saragovi H, Lordkipanidzé M. Inhibition of the p75 pan neurotrophic receptor partly mitigates BDNF-induced platelet aggregation [abstract]. https://abstracts.isth.org/abstract/inhibition-of-the-p75-pan-neurotrophic-receptor-partly-mitigates-bdnf-induced-platelet-aggregation/. Accessed August 16, 2022.« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/inhibition-of-the-p75-pan-neurotrophic-receptor-partly-mitigates-bdnf-induced-platelet-aggregation/