Immature astroglia, rather than neurons, may be targets for epilepsy treatment

We all lose brain cells over time, but the results of a study led by scientists at the University of Southern California (USC) stem cells and the USC Neurorepair Center show that adults lose new brains. Cells that suggest that at least some of the sickness can be replenished, and this process changes dramatically in patients with long-term epilepsy. Results may indicate a new approach to antiepileptic therapy.

“Our study is the first to detail the presence of newborn neurons in patients with epilepsy and the immature version of the associated cell type known as astroglia,” said an assistant professor of stem cell biology and regenerative medicine. Dr. Michael Bonaguidi said. Gerontology, and USC Biomedical Engineering. “Our findings provide amazing new insights into how immature astroglia contribute to epilepsy and are unexplored for the development of new antiepileptic drugs for millions of people. Pave the way for. “

Bonaguidi and colleagues Nature Neuroscience“Changes in adult neurogenesis and glioma formation in patients with mesial temporal epilepsy.. “

The authors explained that adult neurogenesis is a “dramatic form of brain plasticity” in which neonatal neurons and astrocytes modify existing neural circuits. “This process occurs in the dentate gyrus (DG) of the hippocampus, where neonatal cells actively contribute to the regulation of memory and emotion.” However, the team said the rodents of epilepsy. The model pointed out that changes in adult hippocampal neurogenesis can be detrimental. “In rodents, increased cell proliferation, migration, and the formation of abnormal synaptic hippocampal connections can cause seizures.”

The role of adult stem cells in newborns is less clear in humans with epilepsy, and there is evidence of pros and cons of the presence of adult hippocampal neurogenesis in healthy individuals and patients with epilepsy, the researchers continued. “In addition, there are no studies documenting their effects on the prevalence and seizure phenotype of human neonatal neurons with ongoing epilepsy and immature astroglia.”

BonaguidiLab postdoctoral fellow Aswathy Ammothumkandy and her colleagues collaborated with USC neurosurgeons Charles Liu, MD, and Jonathan Russin, MD. They often treat patients with seizures that cannot be controlled by medication. Drug resistance is particularly common in mesial temporal lobe epilepsy, or MTLE, and affects one-third of all patients with this form of disease. As a result, some patients need surgery to remove part of their brain.

For their newly reported study, the team studied tissue from age- and gender-matched controls with adult MTLE patients and conducted cell culture experiments with MTLE to change neurogenesis and stellate formation. I investigated.

“Many patients bravely and generously donate surgical specimens for research to better understand epilepsy and develop new and better treatments,” said USC Neurology, assistant professor of neurosurgery. Russin, Deputy Director of the Restoration Center, said. “These patients are better aware of the trade-offs associated with current treatment options, which often do not provide adequate seizure control or have very serious cognitive side effects.”

Surgical specimens provided a unique opportunity for researchers to study the living brain tissue of epilepsy patients and compare their structure with postmortem samples of people without known neurological disorders. The results confirm the presence of neonatal neurons in samples from individuals with and without epilepsy and are compelling new to the ongoing scientific debate as to whether adults retain the ability to generate these cells. Added evidence.

However, examination of surgical specimens has shown that the longer a patient experiences a seizure, the fewer of these neonatal neurons. Even more surprising, the surgical specimens contained a persistent population of immature astroglia that was not observed in the disease-free sample.

Scientists were able to use the live brain tissue of surgical specimens to test their ability to grow stem cells in the laboratory and form neonatal neurons and immature astrocytes. The results of these experiments, consistent with direct observations by a team of surgical specimens, confirmed that longer disease periods reduced the ability to form neonatal neurons and increased the production of immature astroglia. Their overall result states: Astrogenesis. “

Scientists have individually studied the electrical activity associated with seizures. They found a correlation between where the electrical activity was localized in the surgical sample and the location and behavior of the astroglia.

To summarize their results, the researchers concluded that adult neurogenesis occurs in both healthy humans and epilepsy, but neuronal production declines with the duration of MTLE disease and epilepsy-like activity in DG. “This reduction in neurogenesis can cause some cognitive and emotional deficits that increase in MTLE patients during the course of the disease,” they suggested. However, they further noted that MTLE immature neurons were largely inactive and were not seen in the case of local epilepsy-like activity. Conversely, immature astroglia were present in all MTLE cases, and their location and activity depended on epilepsy-like activity. “Therefore, immature astroglia, rather than neonatal neurons, represent a potential target for continuously regulating hyperactivity in adult human neurons.”

Ammothumkandy said: “Usually, astroglia are thought to support cells because their job is to create an environment in which neurons can thrive. However, in patients who have lived for many years with epilepsy, the onset of chronic seizures. It may be immature astroglia that contribute to both and regulation. ”In this case, immature astroglia are effective in targeting by developing a whole new class of antiepileptic drugs. Can have a different cell type.

“Because currently available seizure drugs tend to target neurons, drugs that act on immature astroglia have the potential to significantly expand patient options,” neurosurgery, neurology, and neurology, and Liu, a professor of biomedical engineering and director of the USC Neurorepair Center, added. Director of the USC Epilepsy Care Consortium. “A new class of medicines is combined with current medical and surgical strategies to control seizures without actively surgically removing parts of the brain that are critical to learning, memory and emotional regulation. can do.”

The authors further pointed out that the remaining important question is whether patients with MTLE retain the potential to regain neurogenesis once lost. “Future studies will define the potential for nerve regeneration in the adult hippocampus,” they said.