Brain-derived Neurotrophic Factor Is Stored in Human Platelets and Released by Agonist Stimulation

Abstract

SummaryBrain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, plays critical roles in the survival, growth, and maintenance of brain and peripheral neurons. We report the presence of BDNF protein in human platelets and its release upon agonist stimulation. The BDNF content of washed platelets varied widely, from 3.5 to 67 ng/ 4 X 108 platelets, averaging 25.2 ± 21.2 ng/4 X 108 platelets (mean ± SD). The BDNF concentration in platelet-poor plasma was low (1.7 ± 1.7 ng/ml, n = 11). Thrombin, collagen, the Ca++ ionophore A23187, and shear stress each induced a rapid release of BDNF from platelets. Up to only half of platelet BDNF was secreted upon agonist stimulation, suggesting that platelets may have a non-releasable pool of BDNF, or that the released BDNF binds to a recognition site on the platelet surface and is internalized, as occurs with serotonin. However, the cognate BDNF receptor, TrkB, was not detected in platelets. Nevertheless, the ability of BDNF to bind washed platelets was shown by FACS analysis confocal microscopy and by the binding and apparent internalization of [125I]-BDNF by platelets. A very high affinity site (Kd = 130 X 10−15 M, ∼80 sites/platelet) and a moderately high affinity site (Kd = 20 nM, ∼3750 sites/platelet) were identified. The BDNF content in two mega-karyocytic cell lines, DAMI and Meg-01, was only 0.1% of the content measured in platelets. No BDNF mRNA was detected by Northern blotting in these cell lines or in platelets. The pituitary gland was also ruled out as a source for platelet BDNF, since the BDNF content of rat platelets did not decrease 2 weeks after hypophysectomy. Thus, platelet BDNF is not acquired from the megakaryocyte or pituitary gland, but is probably acquired from other sources via the blood circulation. Platelets appear to bind, store and release BDNF upon activation at the site of traumatic injury to facilitate the repair of peripheral nerves or other tissues that contain TrkB.

Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

“…2a). Since platelets are known to store and release BDNF [35], we examined the relationship between circulating BDNF and platelet count. The pattern of increase in platelet count (Fig.…”

BDNF rs6265 methylation and genotype interact on risk for schizophrenia

“…However, since the expression of BDNF mRNA does not reflect the rate of protein synthesized, 42 the relationship of BDNF rs6265 methylation with BDNF protein level may also be the result of the contribution of other elements, such as the expression of non-coding transcripts, affecting the level of BDNF protein by acting at a post-transcriptional level. 43,44 Moreover, since human platelets represent a main source of serum BDNF protein but not of BDNF mRNA, serum BDNF has been postulated not to originate from megakaryocyte precursor cells, while potential sources include CNS 41,45,46 ; indeed, it has been shown that BDNF can readily cross the brain-blood barrier. 47 The relationship between rs6265 methylation in PBMCs and serum BDNF levels is therefore compatible with a potential link between rs6265 methylation in PBMCs and in brain.…”

BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits

“…Platelets, brain neurons, and vascular endothelial cells are considered as candidate sources. A major source of the serum BDNF are platelets, which bind, store, and release BDNF upon activation and in response to coagulation stimuli (Yamamoto and Gurney, 1990;Fujimura et al, 2002). As platelets and neurons develop from a common embryonic precursor in the neural crest (Pearse, 1980), the peripheral BDNF concentration could possibly reflect the central neurotransmission state.…”