Repairing Injured Neurons With Optogenetics

Regeneration of injured neurons in living fish has been achieved by scientists at Helmholtz Zentrum München. To this end, they employed optogenetics, i.e. light inducible protein activation.

The nervous system is built to last a lifetime, but diverse diseases or environmental insults can overpower the capacity of neurons to maintain function or to repair after trauma. A team led by Dr. Hernán López-Schier, head of the Research Unit Sensory Biology and Organogenesis at Helmholtz Zentrum München, now succeeded in promoting the repair of an injured neural circuit in zebrafish.

Key for the researchers’ success was the messenger molecule cAMP, which is produced by an enzyme called adenylyl cyclase.

For their experiment, the scientists used a special form of this enzyme which is inducible by blue light. They are thus able to specifically modulate the production of cAMP in cells expressing this enzyme by the use of blue light.

Larval Zebrafish

Larval Zebrafish by CSIRO

The researchers used this system in zebrafish larvae which had interrupted sensory lateralis nerves.

Larvae of zebrafish are particularly well suited for optogenetic approaches, since their skin in transparent/translucent. Thus, the light can reach the respective target cells easily.

“However, when blue light was shone on severed nerves that expressed a photoactivatable adenylyl cyclase, their repair was dramatically increased,” said first author and PhD student Yan Xiao. “While untreated nerve terminals only made synapses again in five percent of the cases, about 30% did after photostimulation.”

In other words, the scientists were able to stimulate the repair of a neuronal circuit by elevating cAMP with blue light.

“Optogenetics have revolutionized neurobiology, since the method has already been used to modify for instance the electrical activity of neurons. However, our results show for the first time how the repair of a complex neural circuit in a whole animal can be promoted remotely by the use of light”, explains López-Schier.

But the head of the study thinks that this is only the beginning:

“Our results are a first step. Now we would like to investigate, whether these results can be extrapolated beyond single neurons in zebrafish, to more complex neuronal circuits of higher animals.”

López-Schier envisions using this method for future therapeutic approaches for the treatment of neuropathies like those occurring in the wake of diabetes and other diseases.

Yan Xiao et al.
Optogenetic stimulation of neuronal repair
Current Biology (2015). DOI: 10.1016/j.cub.2015.09.038

Photo: Nguyen Tan Tin/Flickr

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