Foltran Rocío Beatriz, Stefani Karen Melany, Bonafina Antonela, Resasco Agustina, Diaz Silvina Laura
Instituto de Biología Celular y Neurociencia Prof. E. De Robertis, CONICET - Universidad de Buenos Aires, Buenos Aires, Argentina.
Front Cell Neurosci. 2019 Aug 21;13:384. doi: 10.3389/fncel.2019.00384. eCollection 2019.
Neurotrophic factors are relevant regulators of the neurogenic process at different levels. In particular, the brain-derived neurotrophic factor, BDNF, is highly expressed in the hippocampus (HC) of rodents and participates in the control of neuronal proliferation, and survival in the dentate gyrus (DG). Likewise, serotonin is also involved in the regulation of neurogenesis, though its role is apparently more complex. Indeed, both enhancement of serotonin neurotransmission as well as serotonin depletion, paradoxically increase neuronal survival in the HC of mice. In this study, we analyzed the protein expression of the BDNF isoforms, i.e., pro- and mature-BDNF, and their respective receptors p75 and TrkB, in the HC of mice chronically treated with para-chloro-phenyl-alanine (PCPA), an inhibitor of serotonin synthesis. The same analysis was conducted in hyposerotonergic mice with concomitant administration of the 5-HT receptor agonist, 8-Hydroxy-2-(di-n- propylamino) tetralin (8-OH-DPAT). Increased expression of p75 receptor with decreased expression of pro-BDNF was observed after chronic PCPA. Seven-day treatment with 8-OH-DPAT reestablished the expression of pro-BDNF modified by PCPA, and induced an increase in the expression of p75 receptor. It has been demonstrated that PCPA-treated mice have higher number of immature neurons in the HC. Given that immature neurons participate in the pattern separation process, the object pattern separation test was conducted. A better performance of hyposerotonergic mice was not confirmed in this assay. Altogether, our results show that molecules in the BDNF signaling pathway are differentially expressed under diverse configurations of the serotonergic system, allowing for fine-tuning of the neurogenic process.
神经营养因子是不同水平神经发生过程的相关调节因子。特别是脑源性神经营养因子（BDNF），在啮齿动物的海马体（HC）中高度表达，并参与齿状回（DG）中神经元增殖和存活的控制。同样，血清素也参与神经发生的调节，但其作用显然更为复杂。事实上，血清素神经传递的增强以及血清素的耗竭，都反常地增加了小鼠海马体中神经元的存活。在本研究中，我们分析了用对氯苯丙氨酸（PCPA，一种血清素合成抑制剂）长期处理的小鼠海马体中BDNF亚型（即前体BDNF和成熟BDNF）及其各自受体p75和TrkB的蛋白表达。对血清素能低下的小鼠同时给予5-羟色胺受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）进行了相同的分析。长期使用PCPA后，观察到p75受体表达增加，前体BDNF表达减少。用8-OH-DPAT处理7天可恢复被PCPA改变的前体BDNF的表达，并诱导p75受体表达增加。已经证明，PCPA处理的小鼠海马体中未成熟神经元数量更多。鉴于未成熟神经元参与模式分离过程，进行了物体模式分离测试。在该试验中未证实血清素能低下的小鼠表现更好。总之，我们的结果表明，BDNF信号通路中的分子在血清素能系统的不同配置下差异表达，从而实现对神经发生过程的微调。
