Damage to axons in the central nervous system (CNS) typically results in permanent damage and severed axons in the adult mammalian CNS do not spontaneously regenerate to restore lost functions. Boosting growth programs can dramatically augment the axon regeneration of injured neurons and if injured neurons can regenerate sufficient number of axons, the CNS may recover and overcome functional deficits. It is known that G protein-coupled receptor (GPCR) signaling is essential for axon guidance and targeting during development. However, its function in axonal regeneration in the mature CNS remains elusive. Now, a study from the Hong Kong University of Science and Technology (HKUST) shows that axon regenerative capacity can be boosted with the right stimulants on neuronal activity through either an optogenetic or a chemogenetic approach. The team state that their findings provide evidence for modulating neuronal activity through GPCR signaling in regulating intrinsic axon growth capacity. The opensource study is published in the journal Proceedings of the National Academy of Sciences.
Earlier studies from the lab show that inhibition of the PTEN gene activates mammalian target of rapamycin (mTOR) signaling and promotes corticospinal tract regeneration after spinal cord injury. Neuronal activity has previously been shown to play important roles in axonal sprouting and synaptic plasticity in adult mammals. The current study suggests another role and a mechanism of neuronal activity in axon regeneration, and potentially provides a simple strategy to facilitate neural repair.
The current study utilised mice overexpressing melanopsin in retinal ganglion cells to determine whether melanopsin could promote axonal regeneration. Results show that axonal regeneration was evident after two weeks, and the effect was found to be stimulated by light and neuronal firing, which enhanced and maintained mTOR signaling.
Results show that overexpression of a photopigment, melanopsin, in retinas could enhance neuronal firing of retinal ganglion cells and promote axonal regeneration after optic nerve crush by activating mTOR signaling. Data findings show that axon regeneration can also be promoted by activating Gq signaling in retinal ganglion cells through Designer Receptor Exclusively Activated by Designer Drugs (DREADD), a tool to increase neuronal activity. The group conclude that melanopsin activates Gq/11 signaling that subsequently increases neuronal activity and calcium influx to a degree that may be necessary to sustain long-term mTOR activation in retinal ganglion cells.
The team surmise that their findings show that melanopsin boosts axon regeneration by enhancing mTORC1 in a neuronal activity-dependent manner. For the future, the researchers state that their results provide a strategy to promote axon regeneration after CNS injury by modulating neuronal activity through GPCR signaling.
Michelle Petersen is the founder of Healthinnovations, having worked in the health and science industry for over 21 years, which includes tenure within the NHS and Oxford University. Healthinnovations is a publication that has reported on, influenced, and researched current and future innovations in health for the past decade.
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An avid campaigner in the fight against child sex abuse and trafficking, Michelle is a passionate humanist striving for a better quality of life for all humans by helping to provide traction for new technologies and techniques within healthcare.