Department of Psychiatry, Weill Cornell Medicine, New York, NY, 10065, USA.
Department of Pharmacology, Weill Cornell Medicine, New York, NY, 10065, USA.
Neuropsychopharmacology. 2024 Jan;49(1):227-245. doi: 10.1038/s41386-023-01717-x. Epub 2023 Sep 6.
Neurotrophic factors are a family of growth factors that modulate cellular growth, survival, and differentiation. For many decades, it has been generally believed that a lack of neurotrophic support led to the decreased neuronal synaptic plasticity, death, and loss of non-neuronal supportive cells seen in neuropsychiatric disorders. Traditional psychiatric medications that lead to immediate increases in neurotransmitter levels at the synapse have been shown also to elevate synaptic neurotrophic levels over weeks, correlating with the time course of the therapeutic effects of these drugs. Recent advances in psychiatric treatments, such as ketamine and psychedelics, have shown a much faster onset of therapeutic effects (within minutes to hours). They have also been shown to lead to a rapid release of neurotrophins into the synapse. This has spurred a significant shift in understanding the role of neurotrophins and how the receptor tyrosine kinases that bind neurotrophins may work in concert with other signaling systems. In this review, this renewed understanding of synaptic receptor signaling interactions and the clinical implications of this mechanistic insight will be discussed within the larger context of the well-established roles of neurotrophic factors in psychiatric disorders and treatments.
神经营养因子是一类调节细胞生长、存活和分化的生长因子。几十年来，人们普遍认为，神经营养支持的缺乏导致了神经精神疾病中神经元突触可塑性降低、神经元死亡和非神经元支持细胞丢失。传统的精神药物可立即增加突触处的神经递质水平，也可在数周内提高突触神经营养水平，与这些药物治疗效果的时间进程相关。精神治疗方面的最新进展，如氯胺酮和迷幻剂，显示出更快的治疗效果（数分钟至数小时内）。它们还被证明可导致神经营养因子快速释放到突触中。这极大地改变了人们对神经营养因子作用的理解，以及与神经营养因子结合的受体酪氨酸激酶如何与其他信号系统协同工作。在这篇综述中，将在神经营养因子在精神疾病和治疗中作用的既定背景下，讨论这种对突触受体信号相互作用的新认识及其对机制的临床意义。
