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 scientist used a special form of this enzyme which is inducible by blue light. Therefore, the scientists are able to specifically modulate the production of cAMP in cells expressing this enzyme by the use of blue light.
The researchers used this system in zebrafish larvae which had interrupted sensory lateralis nerves. “However, when blue light was shone on severed nerves that expressed a photoactivatable adenylyl cyclase, their repair was dramatically increased,” remembers PhD student Yan Xiao who is the first author of the study. “While untreated nerve terminals only made synapses again in five percent of the cases, about 30% did after photostimulation.” In simple terms: 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.” The scientist could think of using this method for future therapeutic approaches for the treatment of neuropathies like those occurring in the wake of Diabetes and other diseases.
Further information
Background
- Optogenetics: As the name indicates, this cutting-edge technology combines elements of Optics and Genetics. Scientists make use of proteins which are sensitive to certain wavelengths of light. These are brought into the target cells with certain genetic methods. The so treated cells then change their respective phenotype depending on the exposure to light.
- 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.
- These nerves normally communicate external sensory signals to the brain, but cannot normally repair after injury.
Source: Hernán López-Schier – Helmoltz Zentrum München
Image Credit: The image is credited to Helmholtz Zentrum München
Original Research: Abstract for “Optogenetic stimulation of neuronal repair” by Yan Xiao, Weili Tian, and Hernán López-Schier in Current Biology. Published online November 17 2015 doi:10.1016/j.cub.2015.09.038
Abstract
Optogenetic stimulation of neuronal repair
Environmental insult, disease or trauma can affect the physical integrity of neuronal circuits, and the inability of many neurons to regenerate injured axons invariably leads to irreversible neural dysfunction [1] . The conserved second messenger cyclic adenosine monophosphate (cAMP) can promote axonal re-growth [2–5] . Widely used pharmacological or genetic approaches to increase intracellular levels of cAMP are often inadequate for precise neural-circuit reconstruction because their activity cannot be easily timed to specific target cells. These shortcomings have prevented the controlled repair of pre-defined neurons at selected time points in whole specimens. Thus, technologies to guide neuronal repair in time and space would enable studies of neural-circuit recovery with unprecedented resolution. Towards this aim, we have implemented a proof-of-principle optogenetic method to promote the selective regeneration of refractory axons in a living vertebrate.
“Optogenetic stimulation of neuronal repair” by Yan Xiao, Weili Tian, and Hernán López-Schier in Current Biology. Published online November 17 2015 doi:10.1016/j.cub.2015.09.038
