The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain α-synuclein (α-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that α-syn interacts with and modulates synapsin III. The absence of α-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In α-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in α-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of α-syn and synapsin III in the regulation of dopamine neuron synaptic function.

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SummaryScientific background: Platelet concentrates are nowadays widely applied in different clinical fields to improve soft tissue and bone regeneration. "Concentrated Growth Factors" (CGF) is a new generation of platelet concentrate products, which exhibits an interesting clinical and biotechnological application potential. Aim of the study:The aim of this study is to assess the biological rationale for the use of CGF, by evaluating blood cell localization, the in vitro cumulative release of seven growth factors (PDGF-AB, VEGF, TNF-α, TGF-β1, BDNF, BMP-2 and IGF-1), its in vitro effects on cell proliferation and its mechanical behavior.Methods: CGFs were obtained from volunteer donors. Blood cell localization was evaluated after properly morphological staining and immunohistochemistry. The amount of growth factors release was measured at 5 hours, 1, 3, 6, 7 and 8 days, using ELISA assay. Cells were cultured with and without CGF and their proliferation was evaluated after 72 hours, performing the quantification of Ki-67, using flow cytometry (FACS). The mechanical response of CGF under compression was also attempted. Results:The results showed that platelets and leukocytes were found in a very thin space called "buffy coat", localized between the white and red part of CGF. Each growth factor evaluated, had a specific kinetic release with a great variability among subjects. The in vitro cell proliferation was stimulated. CGF showed an "apparent plasticity" and its mechanical response was influenced by fibrin network structure. Conclusion:These findings support the CGF's clinical use and will allow us to better understand and improve the clinical outcomes. B io lo g y and M e d ic in e

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Platelet concentrates, such as Concentrated Growth Factors (CGF), are autologous preparations obtained from the patient's own blood and rich in platelets, growth factors and cytokines involved in the key processes of tissue regeneration. These autologous concentrates differ in the way of preparation and also in the content of platelets, growth factors and leucocytes, as well as in the fibrin network architecture. So it is difficult to have a standardized product. The aim of the present study was to evaluate how the use of test tubes of different material, for blood collection, could influence the CGF production. Three different test tubes were used and the obtained CGFs were subjected to histomorphological and immunohistochemical analyses. Results showed that the tube material and shape influenced the CGF composition. In fact, according to the type of tube used, the obtained CGFs showed differences in morphology, in the fibrin network architecture and in blood cell localization and distribution.