Regenerating damaged brain tissue is one of the long-sought holy grails of medicine. And while the ambitious quest to grow brand new neurons inside the brains of living patients may never come to pass, a team of Chinese researchers has just demonstrated proof-of-concept success with a brilliant workaround: convert pre-existing cells whose function is to support neurons into neurons themselves. The technique, which is similar in principle to converting adult cells into pluripotent stem cells, could open a new path for unprecedented regenerative therapies for dementia and traumatic brain injuries – if it makes it through the many steps that lie between animal experiments and human trials. “Our study is the first to demonstrate that defined combinations of small molecules can induce the in vivo chemical reprogramming of astrocytes into functional mature neurons with electrophysiological characteristics. Importantly, these in situ-generated [chemically induced neurons] could functionally interact with resident neurons in the brain,” lead author Hongkui Deng and his colleagues at Peking University Health Science Center wrote in a pre-print manuscript. Exemplifying just how complex and difficult to study the brain is, despite decades of neuroscience investigations backed by cutting-edge brain imaging technology, experts are still up in arms about whether or not the human brain is capable of growing new neurons once childhood development has ended. On the other hand, astrocytes, a type of cell found curled intimately around synapses in high numbers throughout the brain, are produced during adulthood. “There are 10 times more astrocytes than neurons, and while neurons die in stroke, the astrocytes around them survive,” Deng told New Scientist. On top of their ubiquity and close association with neurons, Deng and his team decided astrocytes are the ideal target for conversion among all the non-neuron cell types because new ones naturally flock to areas of injury and/or neuron death. A cultured astrocyte showing the hallmark "star" shape that gives the cells their name. The blue dots are stained nuclei of this astrocyte and surrounding cells. In the current study, the small-molecule cocktail was continuously transfused directly into mouse forebrains for two weeks using a small drug pump. Brain samples taken eight weeks later showed that a high percentage of the astrocytes near the transfusion site had morphed into the telltale neuron shape and began producing neuron-specific proteins. And critically, samples taken from mice that lived for one-year post-infusion proved that the astrocyte-to-neuron conversion could last long-term, without retreatment. A series of experiments then confirmed that the CiNs could generate electrical nerve impulses, or action potentials, that underlie neuron-to-neuron communication as quickly as six weeks after injection and formed synapses with neighboring neurons. Though it is impossible to know what the mice’s subjective side effects were, the authors note that no tumors or other detectable health issues arose. Of course, the prospect of adding new neurons into a human brain is mired in both practical and philosophical concerns that cannot currently be answered. What subtypes of neurons can these astrocytes form? How will their interactions with surrounding neurons compare with the neurons they are meant to replace? Will it change a patient’s personality or memories? “If it holds up it’s absolutely amazing, and has a lot of potential applications and exciting consequences,” developmental neurobiologist Matthew Grub told New Scientist. “[But the] chance of this being dangerous is greater than the potential benefits,” says Grubb. “You’d have to have extremely good control over what cells you’re programming, where they’re going to go, and which cells they’ll connect to.” ASTROCYTES, STAINED GREEN, ARE SEEN INTERTWINED WITH MANY SURROUNDING NEURONS IN THIS MICROGRAPH OF A CELL CULTURE. Source
