(Press-News.org) Contact information: Barbara K. Kennedy
science@psu.edu
81-488-634-682
Penn State
Brain repair after injury and Alzheimer's disease
Technology developed to regenerate functional neurons (In vivo reprogramming of reactive glial cells into functional neurons)
Researchers at Penn State University have developed an innovative technology to regenerate functional neurons after brain injury, and also in model systems used for research on Alzheimer's disease. The scientists have used supporting cells of the central nervous system, glial cells, to regenerate healthy, functional neurons, which are critical for transmitting signals in the brain.
Gong Chen, a professor of biology, the Verne M. Willaman Chair in Life Sciences at Penn State, and the leader of the research team, calls the method a breakthrough in the long journey toward brain repair. "This technology may be developed into a new therapeutic treatment for traumatic brain and spinal cord injuries, stroke, Alzheimer's disease, Parkinson's disease, and other neurological disorders," Chen said. The research will be posted online by the journal Cell Stem Cell on 19 December 2013.
When the brain is harmed by injury or disease, neurons often die or degenerate, but glial cells become more branched and numerous. These "reactive glial cells" initially build a defense system to prevent bacteria and toxins from invading healthy tissues, but this process eventually forms glial scars that limit the growth of healthy neurons. "A brain-injury site is like a car-crash site," Chen explained. "Reactive glial cells are like police vehicles, ambulances, and fire trucks immediately rushing in to help -- but these rescue vehicles can cause problems if too many of them get stuck at the scene. The problem with reactive glial cells is that they often stay at the injury site, forming a glial scar and preventing neurons from growing back into the injured areas," he explained.
So several years ago, Chen's lab tested new ways to transform glial scar tissue back to normal neural tissue. "There are more reactive glial cells and fewer functional neurons in the injury site," Chen said, "so we hypothesized that we might be able to convert glial cells in the scar into functional neurons at the site of injury in the brain. This research was inspired by the Nobel prize-winning technology of induced pluripotent stem cells (iPSCs) developed in Shinya Yamanaka's group, which showed how to reprogram skin cells into stem cells," Chen recalled.
Chen and his team began by studying how reactive glial cells respond to a specific protein, NeuroD1, which is known to be important in the formation of nerve cells in the hippocampus area of adult brains. They hypothesized that expressing NeuroD1 protein into the reactive glial cells at the injury site might help to generate new neurons -- just as it does in the hippocampus. To test this hypothesis, his team infected reactive glial cells with a retrovirus that specifies the genetic code for the NeuroD1 protein. "The retrovirus we used is replication-deficient and thus cannot kill infected cells like other viruses found in the wild," Chen said. "More importantly, a retrovirus can infect only dividing cells such as reactive glial cells, but it does not affect neurons, which makes it ideal for therapeutic use with minimal side effect on normal brain functions."
In a first test, Chen and his team investigated whether reactive glial cells can be converted into functional neurons after injecting NeuroD1 retrovirus into the cortex area of adult mice. The scientists found that two types of reactive glial cells -- star-shaped astroglial cells and NG2 glial cells -- were reprogrammed into neurons within one week after being infected with the NeuroD1 retrovirus. "Interestingly, the reactive astroglial cells were reprogrammed into excitatory neurons, whereas the NG2 cells were reprogrammed into both excitatory and inhibitory neurons, making it possible to achieve an excitation-inhibition balance in the brain after reprogramming," Chen said. His lab also performed electrophysiological tests, which demonstrated that the new neurons converted by the NeuroD1 retrovirus could receive neurotransmitter signals from other nerve cells, suggesting that the newly converted neurons had successfully integrated into local neural circuits.
In a second test, Chen and his team used a transgenic-mouse model for Alzheimer's disease, and demonstrated that reactive glial cells in the mouse's diseased brain also can be converted into functional neurons. Furthermore, the team demonstrated that even in 14-month-old mice with Alzheimer's disease -- an age roughly equivalent to 60 years old for humans -- injection of the NeuroD1 retrovirus into a mouse cortex can still induce a large number of newborn neurons reprogrammed from reactive glial cells. "Therefore, the conversion technology that we have demonstrated in the brains of mice potentially may be used to regenerate functional neurons in people with Alzheimer's disease," Chen said.
To ensure that the glial cell-to-neuron conversion method is not limited to rodent animals, Chen and his team further tested the method on cultured human glial cells. "Within 3 weeks after expression of the NeuroD1 protein, we saw in the microscope that human glial cells were reinventing themselves: they changed their shape from flat sheet-like glial cells into normal-looking neurons with axon and dendritic branches," Chen said. The scientists further tested the function of these newly converted human neurons and found that, indeed, they were capable of both releasing and responding to neurotransmitters.
"Our dream is to develop this in vivo conversion method into a useful therapy to treat people suffering from neural injury or neurological disorders," Chen said. "Our passionate motivation for this research is the idea that an Alzheimer's patient, who for a long time was not able to remember things, could start to have new memories after regenerating new neurons as a result of our in vivo conversion method, and that a stroke victim who could not even move his legs might start to walk again."
INFORMATION:
In addition to Chen, other scientists who contributed to this research include Ziyuan Guo, Lei Zhang, Zheng Wu, Yuchen Chen, and Fan Wang, all from Penn State.
The research was funded by Penn State University and the National Institutes of Health.
CONTACTS
Gong Chen: 814-865-2488, gongchen@psu.edu
Barbara Kennedy (PIO): 814-863-4682, science@psu.edu
PHOTO
A high-resolution image is online at http://www.science.psu.edu/news-and-events/2013-news/Chen12-2013 , which is where text will be posted after the journal's news embargo lifts.
PHOTO CAPTION
Researchers at Penn State University led by biologist Gong Chen have developed an innovative technology to regenerate functional neurons after brain injury, and also in model systems used for research on Alzheimer's disease. This technology may be developed into a new therapeutic treatment for traumatic brain and spinal-cord injuries, stroke, Alzheimer's disease, Parkinson's disease, and other neurological disorders. The scientists have used supporting cells of the central nervous system, glial cells, to regenerate healthy and functional neurons, shown in green in this image in the brain of a mouse with Alzheimer's disease. The red areas are the stained nuclei of neuron cells. More information is online at http://www.science.psu.edu/news-and-events/2013-news/Chen12-2013.
GRANT NUMBERS
National Institutes of Health (NIMH083911, MH092740) and Penn State University Eberly College of Science Stem Cell Fund.
Brain repair after injury and Alzheimer's disease
Technology developed to regenerate functional neurons (In vivo reprogramming of reactive glial cells into functional neurons)
2013-12-19
ELSE PRESS RELEASES FROM THIS DATE:
Research linking autism symptoms to gut microbes called 'groundbreaking'
2013-12-19
Research linking autism symptoms to gut microbes called 'groundbreaking'
A new study showing that feeding mice a beneficial type of bacteria can ameliorate autism-like symptoms is "groundbreaking," according to University of Colorado Boulder Professor ...
Modern caterpillars feed at higher temperatures in response to climate change
2013-12-19
Modern caterpillars feed at higher temperatures in response to climate change
Caterpillars of two species of butterflies in Colorado and California have evolved to feed rapidly at higher and at a broader range of temperatures in the past 40 ...
Healthier Happy Meals
2013-12-19
Healthier Happy Meals
Small changes to familiar combo meals can help cut calorie consumption
What would happen if a fast-food restaurant reduces the calories in a children's meal by 104 calories, mainly by decreasing the portion size of French fries? Would children ...
Renegades of cell biology: Why K-Ras gene mutations prove so deadly in cancer
2013-12-19
Renegades of cell biology: Why K-Ras gene mutations prove so deadly in cancer
SALT LAKE CITY—Cells with a mutation in the gene called K-Ras—found in close to 30 percent of all cancers, but mostly those with worst prognosis, such as pancreatic cancer, colon cancer, and lung ...
Researchers find a cause of aging that can be reversed
2013-12-19
Researchers find a cause of aging that can be reversed
Medical researchers have found a cause of ageing in animals that can be reversed, possibly paving the way for new treatments for age-related diseases including cancer, type 2 diabetes, muscle ...
Anti-epilepsy drugs can cause inflammations
2013-12-19
Anti-epilepsy drugs can cause inflammations
RUB physicians investigate how various substances affect glial cells
Physicians at the Ruhr-Universität Bochum (RUB) have been investigating if established anti-epilepsy drugs have anti-inflammatory or pro-inflammatory ...
Emotions in Parkinson's disease
2013-12-19
Emotions in Parkinson's disease
Is it the disease itself or the treatment that impairs the perception of emotions?
Patients affected by Parkinson's disease may experience, in addition to the more obvious motor symptoms (such as tremors ...
Evolution of plumage patterns in male and female birds
2013-12-19
Evolution of plumage patterns in male and female birds
Ducks, geese and swans are waterfowl, an order known to scientists as Anseriformes. Hens, pheasants, partridges and turkeys are game-birds (Galliformes). Both orders are famous not just for their flesh ...
Availability of food increases as countries' dependence on food trade grows
2013-12-19
Availability of food increases as countries' dependence on food trade grows
The figures come out in a study made at Aalto University in Finland examining developments in food availability and food self-sufficiency in 1965. Researchers of Aalto University examined ...
BCG vaccine more effective than previously thought
2013-12-19
BCG vaccine more effective than previously thought
The BCG vaccine has been found to be more effective against the most common form of tuberculosis than previously thought, according to a new study in Clinical Infectious Diseases.
Bacillus ...
LAST 30 PRESS RELEASES:
Premenstrual symptoms linked to increased risk of cardiovascular disease
Newly discovered remains of ancient river landscapes control ice flow in East Antarctica
Newly discovered interstellar object 'may be oldest comet ever seen'
Animal-inspired AI robot learns to navigate unfamiliar terrain
Underserved youth less likely to visit emergency department for concussion in Ontario, study finds
‘Molecular shield’ placed in the nose may soon treat common hay fever trigger
Beetles under climate stress lay larger male eggs: Wolbachia infection drives adaptive reproduction strategy in response to rising temperature and CO₂
Groundbreaking quantum study puts wave-particle duality to work
Weekly injection could be life changing for Parkinson’s patients
Toxic metals linked to impaired growth in infants in Guatemala
Being consistently physically active in adulthood linked to 30–40% lower risk of death
Nerve pain drug gabapentin linked to increased dementia, cognitive impairment risks
Children’s social care involvement common to nearly third of UK mums who died during perinatal period
‘Support, not judgement’: Study explores links between children’s social care involvement and maternal deaths
Ethnic minority and poorer children more likely to die in intensive care
Major progress in fertility preservation after treatment for cancer of the lymphatic system
Fewer complications after additional ultrasound in pregnant women who feel less fetal movement
Environmental impact of common pesticides seriously underestimated
The Milky Way could be teeming with more satellite galaxies than previously thought
New study reveals surprising reproductive secrets of a cricket-hunting parasitoid fly
Media Tip Sheet: Symposia at ESA2025
NSF CAREER Award will power UVA engineer’s research to improve drug purification
Tiny parasitoid flies show how early-life competition shapes adult success
New coating for glass promises energy-saving windows
Green spaces boost children’s cognitive skills and strengthen family well-being
Ancient trees dying faster than expected in Eastern Oregon
Study findings help hone precision of proven CVD risk tool
Most patients with advanced melanoma who received pre-surgical immunotherapy remain alive and disease free four years later
Introducing BioEmu: A generative AI Model that enables high-speed and accurate prediction of protein structural ensembles
Replacing mutated microglia with healthy microglia halts progression of genetic neurological disease in mice and humans
[Press-News.org] Brain repair after injury and Alzheimer's diseaseTechnology developed to regenerate functional neurons (In vivo reprogramming of reactive glial cells into functional neurons)