Department of Veterinary Medicine, University of Teramo, Via R. Balzarini 1, 64100 Teramo, Italy; European Center for Brain Research/IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
European Center for Brain Research/IRCCS Santa Lucia Foundation, Via del Fosso di Fiorano 64, 00143 Rome, Italy; Department of Psychology, Division of Neuroscience and "Daniel Bovet" Neurobiology Research Center, Sapienza University of Rome, Via dei Sardi 70, 00185 Rome, Italy.
Prog Lipid Res. 2023 Jul;91:101239. doi: 10.1016/j.plipres.2023.101239. Epub 2023 Jun 27.
Dentate gyrus of the hippocampus continuously gives rise to new neurons, namely, adult-born granule cells, which contribute to conferring plasticity to the mature brain throughout life. Within this neurogenic region, the fate and behavior of neural stem cells (NSCs) and their progeny result from a complex balance and integration of a variety of cell-autonomous and cell-to-cell-interaction signals and underlying pathways. Among these structurally and functionally diverse signals, there are endocannabinoids (eCBs), the main brain retrograde messengers. These pleiotropic bioactive lipids can directly and/or indirectly influence adult hippocampal neurogenesis (AHN) by modulating, both positively and negatively, multiple molecular and cellular processes in the hippocampal niche, depending on the cell type or stage of differentiation. Firstly, eCBs act directly as cell-intrinsic factors, cell-autonomously produced by NSCs following their stimulation. Secondly, in many, if not all, niche-associated cells, including some local neuronal and nonneuronal elements, the eCB system indirectly modulates the neurogenesis, linking neuronal and glial activity to regulating distinct stages of AHN. Herein, we discuss the crosstalk of the eCB system with other neurogenesis-relevant signal pathways and speculate how the hippocampus-dependent neurobehavioral effects elicited by (endo)cannabinergic medications are interpretable in light of the key regulatory role that eCBs play on AHN.
海马齿状回持续产生新的神经元，即成年新生颗粒细胞，为成熟大脑赋予终生可塑性。在这个神经发生区域内，神经干细胞 (NSCs) 及其后代的命运和行为源自各种细胞自主和细胞间相互作用信号及其潜在途径的复杂平衡和整合。在这些结构和功能多样化的信号中，有内源性大麻素 (eCBs)，它们是大脑的主要逆行信使。这些多效生物活性脂质可以通过正向和负向调节海马龛位中的多种分子和细胞过程，直接和/或间接地影响成年海马神经发生 (AHN)，具体取决于细胞类型或分化阶段。首先，eCB 作为细胞内在因素直接发挥作用，由 NSCs 在受到刺激后自主产生。其次，在许多（如果不是全部）龛位相关细胞中，包括一些局部神经元和非神经元成分，eCB 系统间接调节神经发生，将神经元和神经胶质活动与调节 AHN 的不同阶段联系起来。在此，我们讨论了 eCB 系统与其他与神经发生相关的信号通路的串扰，并推测在考虑 eCB 对 AHN 发挥关键调节作用的情况下，（内）源性大麻素药物引起的海马依赖性神经行为效应如何进行解释。
