Depression and posttraumatic stress disorder are assumed to be maladaptive responses to stress and antidepressants are thought to counteract such responses by increasing BDNF (brain-derived neurotrophic factor) levels. BDNF acts through TrkB (tropomyosin-related receptor kinase B) and plays a central role in neuroplasticity. In contrast, both precursor proBDNF and BDNF propeptide (another metabolic product from proBDNF cleavage) have a high affinity to p75 receptor (p75R) and usually convey apoptosis and neuronal shrinkage. Although BDNF and proBDNF/propeptide apparently act in opposite ways, neuronal turnover and remodeling might be a final common way that both act to promote more effective neuronal networking, avoiding neuronal redundancy and the misleading effects of environmental contingencies. This review aims to provide a brief overview about the BDNF functional role in antidepressant action and about p75R and TrkB signaling to introduce the “continuum-sorting hypothesis.” The resulting hypothesis suggests that both BDNF/proBDNF and BDNF/propeptide act as protagonists to fine-tune antidepressant-dependent neuroplasticity in crucial brain structures to modulate behavioral responses to stress.

抑郁症和创伤后应激障碍被认为是对压力的适应不良反应，而抗抑郁药被认为可以通过增加BDNF（脑源性神经营养因子）水平来抵消这种反应。BDNF通过TrkB（原肌球蛋白相关的受体激酶B）起作用，并在神经可塑性中起重要作用。相反，前体proBDNF和BDNF前肽（来自proBDNF裂解的另一种代谢产物）对p75受体（p75R）具有高亲和力，通常传递细胞凋亡和神经元收缩。尽管BDNF和proBDNF /前肽显然以相反的方式起作用，但是神经元更新和重塑可能是最终的通用方式，两者都可以促进更有效的神经元网络连接，从而避免神经元冗余和环境突发事件的误导性影响。这篇综述旨在简要概述BDNF在抗抑郁作用中的功能，以及有关p75R和TrkB信号传导以引入“连续体分类假说”。由此产生的假设表明，BDNF / proBDNF和BDNF /前肽都可以作为主角来调节关键脑结构中抗抑郁药依赖性神经可塑性，从而调节对应激的行为反应。