AsianScientist (Mar. 7, 2014) – Dr Su Zhida from the Second Military Medical University in Shanghai, along with collaborators at the University of Texas Southwestern (UTSW), has successfully turned scar-forming astrocytes in the spinal cords of adult mice into neurons. Their findings have been published in Nature Communications.
Spinal cord injuries can lead to an irreversible loss of neurons and scarring which ultimately leads to impaired motor and sensory functions. Scientists are hopeful that regenerating cells can repair damage, but adult spinal cords have limited ability to produce new neurons. Stem cell transplants to replace neurons have been attempted, but expose patients to the risk of developing tumors.
In this study, scientists have sought an alternative way to generate new neurons, by coaxing existing cells called astrocytes to turn into neurons.
“Astrocytes are abundant and widely distributed both in the brain and in the spinal cord. In response to injury, these cells proliferate and contribute to scar formation. Once a scar has formed, it seals the injured area and creates a mechanical and biochemical barrier to neural regeneration,” Dr. Zhang Chun-Li of UTSW explained.
“Our results indicate that the astrocytes may be ideal targets for in vivo reprogramming,” he said.
The scientists’ two-step approach first introduces a biological substance that regulates the expression of genes, called a transcription factor, into areas of the brain or spinal cord where that factor is not highly expressed in adult mice. Of 12 transcription factors tested, only SOX2 switched fully differentiated, adult astrocytes to an earlier neuronal precursor, or neuroblast, stage of development, Dr. Zhang said.
In the second step, the researchers gave the mice a drug called valproic acid (VPA) that encouraged the survival of the neuroblasts and their maturation into neurons. VPA has been used to treat epilepsy for more than half a century and also is prescribed to treat bipolar disorder and to prevent migraine headaches, he said.
They observed the formation of new neurons in the spinal cords of both adult and aged mice of both sexes, although the response was much weaker in the aged mice, Dr. Zhang said. Researchers now are searching for ways to boost the number and speed of neuron creation.
Although the research indicates it may someday be possible to regenerate neurons from the body’s own cells to repair traumatic brain injury or spinal cord damage or to treat conditions such as Alzheimer’s disease, the researchers stressed that it is too soon to know whether the neurons created in these initial studies resulted in any functional improvements, a goal for future research.
The article can be found at: Su Z et al. (2014) In vivo conversion of astrocytes to neurons in the injured adult spinal cord.
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Source: University of Texas Southwestern.
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