Astrocytes and brain-derived neurotrophic factor (BDNF)

Abstract

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.