Sbrini Giulia, Brivio Paola, Sangiovanni Enrico, Fumagalli Marco, Racagni Giorgio, Dell'Agli Mario, Calabrese Francesca
Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, 20133 Milan, Italy.
Biomedicines. 2020 Nov 26;8(12):544. doi: 10.3390/biomedicines8120544.
Brain derived neurotrophic factor (Bdnf) is the most diffuse neurotrophin in the central nervous system and it is crucial for the proper brain development and maintenance. Indeed, through the binding to its high affinity receptor TRKB and the activation of different intracellular cascades, it boosts cell survival, neurite growth and spine maturations mechanisms. Here, we evaluated if the chronic oral treatment for 10 days with a phytosomal preparation containing L. and L. could improve Bdnf levels in the prefrontal cortex of adult rats. Interestingly we found an increased expression of Bdnf with main effect of the treatment on the mTOR-S6 downstream signaling pathway. Accordingly, we found an increase in the expression of eukaryotic elongation factor (eEF2) with a shift towards the phosphorylated form thus increasing the transcription of Oligophrenin-1, a protein carrying the upstream Open Reading Frame (uORF) which reduction is paralleled by memory dysfunctions. These results show the ability of the phytosome to enhance mTOR-S6 regulated transcription and suggest the possibility to use this preparation in subjects with impairments in neuroplastic mechanisms, memory and cognitive abilities.
脑源性神经营养因子(Bdnf)是中枢神经系统中分布最广泛的神经营养因子,对大脑的正常发育和维持至关重要。实际上,通过与高亲和力受体TRKB结合并激活不同的细胞内级联反应,它促进细胞存活、神经突生长和脊柱成熟机制。在此,我们评估了用含有L.和L.的植物体制剂进行为期10天的慢性口服治疗是否能提高成年大鼠前额叶皮质中的Bdnf水平。有趣的是,我们发现Bdnf表达增加,且治疗对mTOR - S6下游信号通路有主要影响。相应地,我们发现真核生物延伸因子(eEF2)的表达增加,并向磷酸化形式转变,从而增加了少突素-1的转录,少突素-1是一种携带上游开放阅读框(uORF)的蛋白质,其减少与记忆功能障碍平行。这些结果表明植物体能增强mTOR - S6调节的转录,并提示在神经可塑性机制、记忆和认知能力受损的受试者中使用这种制剂的可能性。