AsianScientist (Feb. 22, 2016) – Although damage to axons in the central nervous system (CNS) typically results in permanent functional deficits, scientists from the Hong Kong University of Science and Technology (HKUST) have demonstrated that regenerative capacity can be boosted with the right stimulants. Their findings have been published in the Proceedings of the National Academy of Science.
Led by the study’s senior author, Assistant Professor Liu Kai, the research team started the investigation on mice by overexpressing the photoreceptor melanopsin in retinal ganglion cells. After two weeks, axons were regenerated in response to light stimulation and neuronal firing, in a manner dependent on mTOR signaling.
To mimic the downstream pathway of melanopsin and also stimulate neuronal activity through a different method, the researchers took a chemogenetic approach by expressing DREADD-Gq in the eyes of the mice. DREADD, short for designer receptor exclusively activated by designer drugs (DREADD), are engineered G-protein coupled receptors that are widely used to non-invasively control neuronal signaling.
When DREADD-Gq was stimulated by the daily administration of the synthetic agonist clozapine-n-oxide, the researchers observed a significant increase in axonal growth, similar to the effect of melanopsin overexpression.
Credit: Division of Life Science, HKUST
“Our results show that melanopsin boosts axon regeneration by enhancing mTORC1 in a neuronal activity-dependent manner,” Liu said. “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.”
In his previous work, Liu had found that inhibition of the PTEN gene would activate mTOR and promote 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. This study suggests another role and a mechanism of neuronal activity in axon regeneration, and potentially provides a simple strategy to facilitate neural repair,” Liu said.
The article can be found at: Li et al. (2016) Promoting Axon Regeneration in the Adult CNS by Modulation of the Melanopsin/GPCR Dignaling.
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Source: Hong Kong University of Science and Technology; Photo: Shutterstock.
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