Satellite glial cells promote regenerative growth in sensory neurons

Abstract

Peripheral sensory neurons regenerate their axon after nerve injury to enable functional recovery. Intrinsic mechanisms operating in sensory neurons are known to regulate nerve repair, but whether satellite glial cells (SGC), which completely envelop the neuronal soma, contribute to nerve regeneration remains unexplored. Using a single cell RNAseq approach, we reveal that SGC are distinct from Schwann cells and share similarities with astrocytes. Nerve injury elicits changes in the expression of genes related to fatty acid synthesis and peroxisome proliferator-activated receptor (PPARα) signaling. Conditional deletion of fatty acid synthase (Fasn) in SGC impairs axon regeneration. The PPARα agonist fenofibrate rescues the impaired axon regeneration in mice lacking Fasn in SGC. These results indicate that PPARα activity downstream of FASN in SGC contributes to promote axon regeneration in adult peripheral nerves and highlight that the sensory neuron and its surrounding glial coat form a functional unit that orchestrates nerve repair.

Transcriptional profiling of mouse peripheral nerves to the single-cell level to build a sciatic nerve ATlas (SNAT)

“…We have integrated our data in a freely accessible and searchable web interface ( https://www.snat.ethz.ch ) with the intention to make a contribution to the filling of a gap in current peripheral nerve research. Using this resource as baseline, together with recently published complementary extensions mainly focusing on immune cells in peripheral nerves ( Kalinski et al, 2020 ; Wang et al, 2020 ; Ydens et al, 2020 ) and adult nerves ( Wolbert et al, 2020 ), we anticipate that there will be expanding efforts to cover various aspects of peripheral nerve biology such as in cellular-, injury-, aging-, and disease models ( Toma et al, 2020 ) as well as covering other related glia cells ( Avraham et al, 2020 ; Stierli et al, 2019 ), hopefully yielding insightful and valuable data as the fundamental basis of building and testing hypothesis in functional follow-up studies.…”

Satellite Glial Cells in Pain Research: A Targeted Viewpoint of Potential and Future Directions

“…Data showed that microencapsulated SC transplantation could block the expression of the purinergic receptor P2X3 in the DRG and diminish the behavioral components of a neuropathic pain model (77). It is not yet known whether such a method can be applicable for SGCs considering that fatty acid synthesis in SGCs has been identified as a crucial step in nerve repair in adults after peripheral nerve injury (69).…”

A Fenofibrate Diet Prevents Paclitaxel-Induced Peripheral Neuropathy in Mice

“…Thus, the protective effect of fenofibrate treatment observed here could be explained by a reduction in nerve fiber degeneration and/or stimulation of nerve fiber regrowth. Recently, fenofibrate has been shown to promote the sensory nerve fiber response in a model of traumatic nerve injury by activation of PPAR-α receptors [ 16 ]. The results of this study suggest that fenofibrate can be used to activate PPAR-α receptors in the satellite glial cells of DRG and improve the regeneration and growth of sensory axons following injury to dorsally projecting nerves in the spinal cord or repair of peripheral nerves [ 16 ].…”

“…In addition, exogenous PPAR-α agonists such as fenofibrate have been shown to exert analgesic and neuroprotective effects in rodent models of chronic neuropathic pain and inflammation as well as in some human studies [ 8 , 9 , 10 ]. Very recently, activation of PPAR-α by fenofibrate has also been shown to promote sensory nerve fiber regrowth in a model of traumatic nerve injury [ 16 ]. Fenofibrate is a Food and Drug Administration (FDA)-approved drug for the treatment of dyslipidemia.…”