Department of Experimental Medicine, University of Genova, Italy; IIT Center for Synaptic Neuroscience and Technology, Genova, Italy.
IIT Center for Synaptic Neuroscience and Technology, Genova, Italy; Department of Life Sciences, University of Trieste, Italy.
Neurosci Res. 2023 Dec;197:42-51. doi: 10.1016/j.neures.2023.02.001. Epub 2023 Feb 11.
Astrocytes are emerging in the neuroscience field as crucial modulators of brain functions, from the molecular control of synaptic plasticity to orchestrating brain-wide circuit activity for cognitive processes. The cellular pathways through which astrocytes modulate neuronal activity and plasticity are quite diverse. In this review, we focus on neurotrophic pathways, mostly those mediated by brain-derived neurotrophic factor (BDNF). Neurotrophins are a well-known family of trophic factors with pleiotropic functions in neuronal survival, maturation and activity. Within the brain, BDNF is the most abundantly expressed and most studied of all neurotrophins. While we have detailed knowledge of the effect of BDNF on neurons, much less is known about its physiology on astroglia. However, over the last years new findings emerged demonstrating that astrocytes take an active part into BDNF physiology. In this work, we discuss the state-of-the-art knowledge about astrocytes and BDNF. Indeed, astrocytes sense extracellular BDNF through its specific TrkB receptors and activate intracellular responses that greatly vary depending on the brain area, stage of development and receptors expressed. Astrocytes also uptake and recycle BDNF / proBDNF at synapses contributing to synaptic plasticity. Finally, experimental evidence is now available describing deficits in astrocytic BDNF in several neuropathologies, suggesting that astrocytic BDNF may represent a promising target for clinical translation.
星形胶质细胞在神经科学领域中作为大脑功能的关键调节剂而崭露头角,从突触可塑性的分子控制到协调认知过程中的全脑电路活动。星形胶质细胞调节神经元活动和可塑性的细胞途径非常多样化。在这篇综述中,我们重点介绍神经营养途径,主要是由脑源性神经营养因子 (BDNF) 介导的途径。神经营养因子是一类具有多种功能的已知的营养因子,可促进神经元的存活、成熟和活性。在大脑中,BDNF 是所有神经营养因子中表达最丰富、研究最多的一种。虽然我们详细了解了 BDNF 对神经元的作用,但对其在星形胶质细胞上的生理学功能知之甚少。然而,近年来的新发现表明,星形胶质细胞积极参与了 BDNF 的生理学过程。在这项工作中,我们讨论了关于星形胶质细胞和 BDNF 的最新知识。事实上,星形胶质细胞通过其特异性的 TrkB 受体感知细胞外 BDNF,并激活细胞内反应,这些反应因大脑区域、发育阶段和表达的受体而异。星形胶质细胞还在突触处摄取和再循环 BDNF/ proBDNF,有助于突触可塑性。最后,现在有实验证据描述了几种神经病理学中星形胶质细胞 BDNF 的缺陷,表明星形胶质细胞 BDNF 可能代表一个有前途的临床转化靶点。