Immature embryonic neurons are able to integrate and repair functionality in damaged brain regions in adult mice
The brain has a rather poor ability to regenerate itself for the most part, and damage frequently remains permanent following injury. Developing cell therapy methods to reconnect lost connections and repair lesions is therefore a major target of regenerative medicine today.
Using immature neurons
In a new study published in Nature, researchers have demonstrated that embryonic neurons are able to mature and become assimilated into neural circuits in damaged brain tissue. They began the research by using a laser to cause precise lesions in the visual cortex in mice. They then isolated immature neurons from the outer layer of mouse embryos; labelling them with a fluorescent tag to keep an eye on their behaviour and movement. Adult neurons are less 'plastic', and while the immature neurons were foreign, they are not immunogenic - meaning they don't create a damaging immune reaction.
The team then transplanted these neurons into the brain lesions they had formed in these adult mice. In order to view the implanted neurons, they removed a small square of skull above the site and inserted a transparent glass panel. Over a month, the neurons began sprouting branches typical of a cortical neuron type, which are present in the visual cortex. They also developed features called spines on their newly branching connections, which is a feature typical of normal brain development. Spines host synapses, which allow communication with other neurons.
To their surprise the researchers found that the implanted neurons were able to successfully form a large number of new connections, both nearby and across the entire brain. This pattern was extremely similar to the original neurons in the cortex that had been destroyed.
“To date, this is the most comprehensive study of the circuit integration of transplanted neurons into the adult brain, and the only study so far to follow the integration of individual cells throughout their life span in the new host”
Not only did these neurons prove able to rewire themselves into the existing brain tissue, they also mirrored the specific cell type they were designed to replace - V1 neurons. V1 is a region of the visual cortex that responds to very specific visual stimuli, such as the orientation of lines. WIthout this carefully orchestrated sensitivity, rogue neurons could mess up the entire system's signals. The implanted neurons were actually able to mimic these neuron types, responding in a similar manner to this stimuli as they should, by 15 weeks post-transplantation.
“These findings demonstrate that the implanted nerve cells have integrated with high precision into a neuronal network into which, under normal conditions, new nerve cells would never have been incorporated. This proof-of-principle study shows that…the lesioned adult brain is still capable of integrating new building blocks. Neuronal replacement therapies may be realistic, at least at times when a sufficient part of the pre-existing neuronal network is still available”
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