Posts tagged glial cells
Articles and news from the latest research reports.
(Image caption: This microscope image of tissue from deep inside a normal mouse ear shows how ribbon synapses (red) form the connections between the hair cells of the inner ear (blue) and the tips of nerve cells (green) that connect to the brain. Credit: Corfas Lab, University of MIchigan)
Scientists Restore Hearing in Noise-Deafened Mice, Pointing Way to New Therapies
Scientists have restored the hearing of mice partly deafened by noise, using advanced tools to boost the production of a key protein in their ears.
By demonstrating the importance of the protein, called NT3, in maintaining communication between the ears and brain, these new findings pave the way for research in humans that could improve treatment of hearing loss caused by noise exposure and normal aging.
In a new paper in the online journal eLife, the team from the University of Michigan Medical School’s Kresge Hearing Research Institute and Harvard University report the results of their work to understand NT3’s role in the inner ear, and the impact of increased NT3 production on hearing after a noise exposure.
Their work also illustrates the key role of cells that have traditionally been seen as the “supporting actors” of the ear-brain connection. Called supporting cells, they form a physical base for the hearing system’s “stars”: the hair cells in the ear that interact directly with the nerves that carry sound signals to the brain. This new research identifies the critical role of these supporting cells along with the NT3 molecules that they produce.
NT3 is crucial to the body’s ability to form and maintain connections between hair cells and nerve cells, the researchers demonstrate. This special type of connection, called a ribbon synapse, allows extra-rapid communication of signals that travel back and forth across tiny gaps between the two types of cells.
“It has become apparent that hearing loss due to damaged ribbon synapses is a very common and challenging problem, whether it’s due to noise or normal aging,” says Gabriel Corfas, Ph.D., who led the team and directs the U-M institute. “We began this work 15 years ago to answer very basic questions about the inner ear, and now we have been able to restore hearing after partial deafening with noise, a common problem for people. It’s very exciting.”
Using a special genetic technique, the researchers made it possible for some mice to produce additional NT3 in cells of specific areas of the inner ear after they were exposed to noise loud enough to reduce hearing. Mice with extra NT3 regained their ability to hear much better than the control mice.
Now, says Corfas, his team will explore the role of NT3 in human ears, and seek drugs that might boost NT3 action or production. While the use of such drugs in humans could be several years away, the new discovery gives them a specific target to pursue.
Corfas, a professor and associate chair in the U-M Department of Otolaryngology, worked on the research with first author Guoqiang Wan, Ph.D., Maria E. Gómez-Casati, Ph.D., and others in his former institution, Harvard. Some of the authors now work with Corfas in his new U-M lab. They set out to find out how ribbon synapses – which are found only in the ear and eye – form, and what molecules are important to their formation and maintenance.
Anyone who has experienced problems making out the voice of the person next to them in a crowded room has felt the effects of reduced ribbon synapses. So has anyone who has experienced temporary reduction in hearing after going to a loud concert. The damage caused by noise – over a lifetime or just one evening – reduces the ability of hair cells to talk to the brain via ribbon synapse connections with nerve cells.
Targeted genetics made discovery possible
After determining that inner ear supporting cells supply NT3, the team turned to a technique called conditional gene recombination to see what would happen if they boosted NT3 production by the supporting cells. The approach allows scientists to activate genes in specific cells, by giving a dose of a drug that triggers the cell to “read” extra copies of a gene that had been inserted into them. For this research, the scientists activated the extra NT3 genes only into the inner ear’s supporting cells.
The genes didn’t turn on until the scientists wanted them to – either before or after they exposed the mice to loud noises. The scientists turned on the NT3 genes by giving a dose of the drug tamoxifen, which triggered the supporting cells to make more of the protein. Before and after this step, they tested the mice’s hearing using an approach called auditory brainstem response or ABR – the same test used on humans.
The result: the mice with extra NT3 regained their hearing over a period of two weeks, and were able to hear much better than mice without the extra NT3 production. The scientists also did the same with another nerve cell growth factor, or neurotrophin, called BDNF, but did not see the same effect on hearing.
Next steps
Now that NT3’s role in making and maintaining ribbon synapses has become clear, Corfas says the next challenge is to study it in human ears, and to look for drugs that can work like NT3 does. Corfas has some drug candidates in mind, and hopes to partner with industry to look for others.
Boosting NT3 production through gene therapy in humans could also be an option, he says, but a drug-based approach would be simpler and could be administered as long as it takes to restore hearing.
Corfas notes that the mice in the study were not completely deafened, so it’s not yet known if boosting NT3 activity could restore hearing that has been entirely lost. He also notes that the research may have implications for other diseases in which nerve cell connections are lost – called neurodegenerative diseases. “This brings supporting cells into the spotlight, and starts to show how much they contribute to plasticity, development and maintenance of neural connections,” he says.
(Image caption: Neurons (blue) which have absorbed exosomes (green) have increased levels of the enzyme catalase (red), which helps protect them against peroxides. Credit: Institute of Molecular Cell Biology)
Vesicles influence the function of nerve cells
Tiny vesicles containing protective substances which they transmit to nerve cells apparently play an important role in the functioning of neurons. As cell biologists at Johannes Gutenberg University Mainz (JGU) have discovered, nerve cells can enlist the aid of mini-vesicles of neighboring glial cells to defend themselves against stress and other potentially detrimental factors. These vesicles, called exosomes, appear to stimulate the neurons on various levels: they influence electrical stimulus conduction, biochemical signal transfer, and gene regulation. Exosomes are thus multifunctional signal emitters that can have a significant effect in the brain.
The researchers in Mainz already observed in a previous study that oligodendrocytes release exosomes on exposure to neuronal stimuli. These exosomes are absorbed by the neurons and improve neuronal stress tolerance. Oligodendrocytes are a type of glial cell and they form an insulating myelin sheath around the axons of neurons. The exosomes transport protective proteins such as heat shock proteins, glycolytic enzymes, and enzymes that reduce oxidative stress from one cell type to another, but also transmit genetic information in the form of ribonucleic acids.
"As we have now discovered in cell cultures, exosomes seem to have a whole range of functions," explained Dr. Eva-Maria Krämer-Albers. By means of their transmission activity, the small bubbles that are the vesicles not only promote electrical activity in the nerve cells, but also influence them on the biochemical and gene regulatory level. "The extent of activities of the exosomes is impressive," added Krämer-Albers. The researchers hope that the understanding of these processes will contribute to the development of new strategies for the treatment of neuronal diseases. Their next aim is to uncover how vesicles actually function in the brains of living organisms.
Study Identifies Unexpected Clue to Peripheral Neuropathies
New research shows that disrupting the molecular function of a tumor suppressor causes improper formation of a protective insulating sheath on peripheral nerves – leading to neuropathy and muscle wasting in mice similar to that in human diabetes and neurodegeneration.
Scientists from Cincinnati Children’s Hospital Medical Center report their findings online Sept. 26 in Nature Communications. The study suggests that normal molecular function of the tumor suppressor gene Lkb1 is essential to an important metabolic transition in cells as peripheral nerves (called axons) are coated with the protective myelin sheath by Schwann glia cells.
“This study is just the tip of the iceberg and a fundamental discovery because of the unexpected finding that a well-known tumor suppressor gene has a novel and important role in myelinating glial cells,” said Biplab Dasgupta PhD, principal investigator and a researcher at the Cincinnati Children’s Cancer and Blood Diseases Institute (CBDI). “Additional study is needed, as the function of Lkb1 may have broader implications – not only in normal development, but also in metabolic reprogramming in human pathologies. This includes functional regeneration of axons after injury and demyelinating neuropathies.”
The process of myelin sheath formation (called myelination) requires extraordinarily high levels of lipid (fat) synthesis because most of myelin is composed of lipids, according to Dasgupta. Lipids are made from citric acid which is produced in the powerhouse of cells called mitochondria. Success of this sheathing process depends on the cells shifting from a glycolytic to mitochondrial oxidative metabolism that generates citric acid, the authors report.
Dasgupta’s research team used Lkb1 mutant mice in the current study. Because the mice did not express Lkb1 in myelin forming glial cells, this allowed scientists to analyze its role in glial cell metabolism and formation of the myelin sheath coating.
When the function of Lkb1 was disrupted in laboratory mice, it blocked the metabolic shift from glycolytic to mitochondrial metabolism, resulting in a thinner myelin sheath (hypomyelination) of the nerves. This caused muscle atrophy, hind limb dysfunction, peripheral neuropathy and even premature death of these mice, according to the authors.
Peripheral neuropathy involves damage to the peripheral nervous system – which transmits information from the brain and spinal cord (the central nervous system) to other parts of the body, according to the National Institute of Neurological Disorders and Stroke (NINDS). There are more than 100 types of peripheral neuropathy, and damage to the peripheral nervous system interferes with crucial messages from the brain to the rest of the body.
The scientists also reported that reducing Lkb1 in Schwann cells decreased the activity of critical metabolic enzyme citrate synthase that makes citric acid. Enhancing Lkb1 increased this activity.
They tested the effect of boosting citric acid levels in the Lbk1 mutant Schwann cells. This enhanced lipid production and partially reversed myelin sheath formation defects in Lbk1 mutant Schwann cells. Dasgupta said this further underscores the importance of Lbk1 and the production of citrate synthase.
Dasgupta and his colleagues are currently testing whether increasing the fat content in the Lbk1 mutant mice diet improves hypomyelination defects. The researchers emphasized the importance of additional research into the laboratory findings to extend their relevance more directly to human disease.
(Source: cincinnatichildrens.org)
Mouse model for epilepsy, Alzheimer’s gives window into the working brain
University of Utah scientists have developed a genetically engineered line of mice that is expected to open the door to new research on epilepsy, Alzheimer’s and other diseases.
The mice carry a protein marker, which changes in degree of fluorescence in response to different calcium levels. This will allow many cell types, including cells called astrocytes and microglia, to be studied in a new way.
"This is opening up the possibility to decipher how the brain works," said Petr Tvrdik, Ph.D., a research fellow in human genetics and a senior author on the study.
The research was published Aug. 14, 2014, in Neuron, a world-leading neuroscience journal. The work is the result of a three-year study involving multiple labs connected with The Brain Institute at the University of Utah. The lead author is J. Michael Gee, who is pursuing both a medical degree and a graduate degree in bioengineering at the university.
"We’re really in the era of team science," said John White, Ph.D., professor of bioengineering, executive director of the Brain Institute and the study’s corresponding author.
With the new mouse line, scientists can use a laser-based fluorescence microscope to study the calcium indicator in the glial cells of the living mouse, either when the mouse is anesthetized or awake. Calcium is studied because it is an important signaling molecule in the body and it can reveal how well the brain is functioning.
Using this method, the scientists are essentially creating a window into the working brain to study the interactions between neurons, astrocytes and microglia.
"We believe this will give us new insights for treatments of epilepsy and for new views of how the immune system of the brain works," White said.
About one-third of the 3 million Americans estimated to have epilepsy lack adequate treatment to manage the disease.
Describing a long-standing collaboration with fellow university researcher and professor of pharmacology and toxicology Karen Wilcox, Ph.D., White said, “We believe the glial cells are malfunctioning in epilepsy. What we’re trying to do is find out in what ways astrocytes participate in the disease.”
This research is expected to lead to new classes of drugs.
The ability to track calcium changes in microglial cells will also open up the possibility of studying inflammatory diseases of the brain. Every neurological disease, including Multiple Sclerosis and Alzheimer’s, appears to include components of inflammation, the scientists said.
"Live imaging and monitoring microglial activity and responses to inflammation was not possible before," said Tvrdik, particularly in living animals. In the past, researchers studied post-mortem tissue or relied on invasive approaches using synthetic dyes.
(Source: eurekalert.org)
Stem Cell Therapies Hold Promise, But Obstacles Remain
In an article appearing online today in the journal Science, a group of researchers, including University of Rochester neurologist Steve Goldman, M.D., Ph.D., review the potential and challenges facing the scientific community as therapies involving stem cells move closer to reality.
The review article focuses on pluripotent stem cells (PSCs), which are stem cells that can give rise to all cell types. These include both embryonic stem cells, and those derived from mature cells that have been “reprogrammed” or “induced” – a process typically involving a patient’s own skin cells – so that they possess the characteristics of stem cells found at the earliest stage of development. These cells can then be differentiated, through careful manipulation of chemical and genetic signaling, to become virtually any cell type found in the body.
While the process of making induced PSCs is relatively new in scientific terms – it was first demonstrated that skin cells could be successfully reprogrammed in 2007 – one of the reasons that these cells are viewed with promise by the scientific community is because they are derived from the patient’s own tissue. Consequently, cells used for transplant can be a genetic match and far less likely to be rejected, thereby potentially mitigating the need to use immune system suppressing drugs.
The article addresses the current state of efforts to apply PSCs to treat a number of diseases, including diabetes, liver disease, and heart disease. Goldman, a distinguished professor and co-director of the University of Rochester School of Medicine and Dentistry Center for Translational Neuromedicine, reviewed the current state of therapies for neurological diseases.
While progress has been made over the last several years, the authors point out that significant challenges remain. Scientists must be able to obtain the precise cell populations required to treat the target disease, and once transplanted, make sure that these cells get to where they are needed and integrate into existing tissue. The cells that are transplanted must also first be checked for purity and screened for unwanted cells that could give rise to tumors.
Goldman and his co-authors contend that “the brain is arguable the most difficult of the organs in which to employ stem cell-based therapeutics.” The complex connections and interdependency between neurons and the myriad of other support cells found in central nervous mean that a precise reconstruction of damaged areas of the brain is often impractical. Also, many degenerative neurological disorders, including Alzheimer’s, involve more than one cell type, making them difficult targets for stem cell therapies, at least in the near future.
Instead, Goldman argues that neurological diseases that involve a single cell type – at least at the early stages – are more promising targets for PSC-based therapies. These include Parkinson’s disease and Huntington’s disease, which are characterized by the loss of dopamine-producing neurons and medium spiny neurons, respectively. In particular, diseases that involved support cells found in the brain known as glia – such as multiple sclerosis, white matter stroke, cerebral palsy, and pediatric leukodystrophies – are especially strong candidates for stem cell therapies. These diseases are characterized by the loss of a specific glial cell type called the oligodendrocyte, which makes myelin, the insulation that allows electrical signals to travel between nerve cells. In multiple sclerosis, the body’s own immune system attacks and destroys these cells and, over time, communication between cells is disrupted or even lost.
Oligodendrocytes are the offspring of another cell called the oligodendrocyte progenitor cell, or OPC. Scientists have long speculated that, if successfully transplanted into the diseased or injured brain, OPCs might be able to produce new oligodendrocytes capable of restoring lost myelin, thereby reversing the damage caused by these diseases.
Goldman’s group has already shown that OPCs produced from PSCs obtained from human skin cells successfully restore myelin in the brains and spinal cords of myelin-deficient mice, and can rescue and restore function to mice that would have otherwise died. While this work demonstrated the promise of stem cell therapies, it also illustrated the challenges facing scientists. It took Goldman’s lab four years to establish the exact chemical signaling required to reprogram, produce, and ultimately purify OPCs in sufficient quantities for transplantation, and only recently has the group developed methods for producing the cells in purity and quantity sufficient to transplant into humans.
The authors contend that future progress will depend upon continued close collaboration between scientists and clinicians, and between academia, industry and regulatory bodies to overcome the remaining barriers to bringing new stem cell-based therapies to patients with these devastating diseases.
Molecular imbalance linked to brain tumour seizures
Researchers in France may have discovered why some patients with a type of brain tumour have epileptic seizures.
“This small study is interesting and shows that glioma-linked epilepsy may be connected to certain channels found in the membranes of nerve cells” - Dr Robin Grant, Edinburgh Cancer Research UK Centre
Their study, published in Science Translational Medicine, suggests that seizures in patients with glioma may be linked to an imbalance of chloride – which is involved in nerve activity – in certain brain cells.
Whether a patient has seizures is linked to how aggressive their tumour is – with less aggressive cases being more prone to epilepsy as tumour cells slowly progress and alter brain tissue.
It is hoped that further research could explore treatments for glioma-linked epilepsy by controlling chloride levels in the brain.
Glioma develops from specialised brain cells known as ‘glial cells’ that usually help to keep brain nerve cells in place, providing support and protection to ensure correct brain function.
In the latest study, scientists from Sorbonne University studied brain tissue samples from 47 glioma patients and found that nerve tissue infiltrated by glioma cells behaves in similar ways to other forms of epilepsy.
Looking at the patient samples, the team found that a particular type of nerve cell – called a pyramidal cell – released excessive amounts of chloride from inside the cells when exposed to a molecule called GABA, which is also involved in transmitting nerve signals.
GABA was released by other neighbouring nerve cells called ‘interneurons’. And the researchers believe that the release of chloride through specialised molecular channels in the membrane of nerve cells, may be responsible for the seizures experienced in some glioma patients.
Dr Robin Grant, an expert in epilepsy and glioma from the Edinburgh Cancer Research UK Centre, who was not involved in the research, said that the channels may make good drug targets for further investigation, but a finer understanding of the involvement of other processes is still needed.
“This small study is interesting and shows that glioma-linked epilepsy, as with other types of epilepsy, may be connected to certain channels found in the membranes of nerve cells.
“More research will be needed to understand the finer details of this process in glioma and whether these channels, along with other similar channels found in nerve cells, could be good targets for drugs to help control the condition.”
Study shows how brain tumor cells move and damage tissue, points to possible therapy
Researchers at the University of Alabama at Birmingham have shed new light on how cells called gliomas migrate in the brain and cause devastating tumors. The findings, published June 19, 2014 in Nature Communications, show that gliomas — malignant glial cells — disrupt normal neural connections and hijack control of blood vessels.
The study provides insight into the mechanisms of how glioma cells spread throughout the brain as a devastating form of brain cancer, and potentially offers a tantalizing opportunity for therapy.
A hallmark of gliomas is that the cells can migrate away from a central tumor, invading healthy brain tissue. Even if a tumor mass is surgically removed, malignant cells that have migrated are left behind, and can grow into a new tumor.
To grow, glioma cells need access to nutrients in the blood supply, and it is known that gliomas travel along blood vessels within the brain. Now, researchers in the lab of neuroscientist Harald Sontheimer, Ph.D., professor in the UAB Department of Neurobiology, have discovered that, as they move, gliomas dislodge astrocytic endfeet, which play a critical role in regulating blood flow in the brain.
Astrocytes are star-shaped cells in the brain that surround blood vessels and connect to them through projections called endfeet, which extend from the astrocyte and latch onto the vessel wall. The surface of nearly every blood vessel in the brain is covered by endfeet, which regulate the smooth muscle cells on the walls of blood vessels. Through that connection, instructions can be given to the muscle cells to constrict the blood vessel and limit blood flow, or dilate the vessel and increase blood flow.
Sontheimer, director of the UAB Center for Glial Biology in Medicine, says that, as a person performs different neurological functions, blood flow needs to be increased to the areas responsible for that function and correspondingly decreased in other areas to maintain balance.
The arrival of a glioma cell changes all that.
“Glioma cells traveling along blood vessels literally cut the connection of astrocytic endfeet with the vessels and push them out of the way,” said Sontheimer. “By disrupting this important neural connection, adverse cognitive effects could be expected. Additionally, our study showed that gliomas then take control of the blood vessels for their own ends. And those ends are primarily to obtain nutrients from blood so that they can continue to grow and spread.”
Sontheimer’s team says the glioma cells tend to congregate at blood vessel junctions, almost as if camping alongside a stream where it joins a river. The ready supply of nutrients would allow the cell to grow into a larger tumor mass.
By traveling on the outside of a blood vessel, glioma cells are able to access nutrients from the blood stream. As a side effect to that process, they damage the blood brain barrier. The barrier, a layer of endothelial cells, protects the brain by restricting passage of harmful substances from the blood stream into brain tissue.
“We found that, when gliomas push away the astrocytic endfeet, damage occurs to the integrity of the endothelial cells that make up the blood brain barrier,” said Stefanie Robel, Ph.D., a postdoctoral researcher in Sontheimer’s lab and co-first author of the study. “The barrier becomes weakened, and begins to leak. A leak across the barrier can cause severe damage to brain tissue.”
“That leakage appears to be a consequence of glioma cells’ migrating along the blood vessels in their search for nutrients,” said Stacey Watkins, an M.D./Ph.D. student in Sontheimer’s lab and co-first author. “When glioma cells contact the vessels, they have direct access to nutrients.”
But amid the deleterious effects that Sontheimer’s team observed — shearing away the endfeet from their blood vessels, disrupting normal brain activity, hijacking control of blood vessels and causing leaks in the blood brain barrier — he says there may be a silver lining. The idea that gliomas cause the blood brain barrier to become porous and leak might open up a new avenue to kill the malignant cells as they migrate.
Chemotherapy, usually delivered intravenously, is not considered an effective strategy for killing gliomas. Chemotherapeutic agents are very effective in killing cancer cells elsewhere in the body, but the predominant belief is that such drugs will not pass the blood brain barrier and thus will not reach their target.
“Chemotherapy is typically not tried in cases of glioma until after other therapies such as surgery and radiation have been employed,” Sontheimer said. “Our findings, which suggest that gliomas actually weaken the blood brain barrier and cause leakage, might indicate that high-dose, intravenous chemotherapy used early on following a diagnosis of brain cancer would be beneficial.”
The study, funded by the National Institutes of Health and the American Brain Tumor Association, was conducted on a clinically relevant mouse model of human malignant glioma.
Sontheimer says logical next steps would be to further examine the cognitive impact of severing the astrocytic endfeet connection to blood vessels.
Unexpected origin for important parts of the nervous system
A new study from Karolinska Institutet shows that a part of the nervous system, the parasympathetic nervous system, is formed in a way that is different from what researchers previously believed. In this study, which is published in the journal Science, a new phenomenon is investigated within the field of developmental biology, and the findings may lead to new medical treatments for congenital disorders of the nervous system.
Almost all of the body’s functions are controlled by the autonomous, involuntary nervous system, for example the heart and blood vessels, liver and gastrointestinal system. At rest, the body is set up for energy saving functions, which is regulated by the parasympathetic part of the autonomous nervous system.
Current understanding is that many important types of cells, including the parasympathetic nerve cells in various organs, originate in early progenitor cells that move short distances while the embryo is still small. But this model does not explain how many of our organs – which develop relatively late, when the embryo is large – are furnished with cells that form the parasympathetic neurons.
This study alters a fundamental principal of our understanding of how the peripheral nervous system develops in the body. Researchers at Karolinska Institutet have made three-dimensional reconstructions of mouse embryos. These show that the parasympathetic neurons are formed from immature glial cells known as Schwann cell precursors that travel along the peripheral nerves out to the body’s tissues and organs. The immature cells have the properties of stem cells and may be the origin of several different types of cells. For example, the researchers behind this new study have previously demonstrated that the majority of our melanocytes (pigment cells) are born from these cells.
New principal of developmental biology
"Our study focuses on a new principal of developmental biology, a targeted recruitment of cells that are probably also used in the reconstruction of tissue. Despite the elegance, simplicity and beauty of this principal, it is still unclear how the number of parasympathetic neurons is controlled and why only some of the cells transported by nerves are transformed into that which becomes an important part of the nervous system", says Igor Adameyko at the Department of Physiology and Pharmacology who, together with Patrik Ernfors at the Department of Medical Biochemistry and Biophysics, is responsible for the study.
Somewhat surprisingly, the researchers found that the entire parasympathetic nervous system arises from these progenitor cells that travel along the peripheral nerves. The researchers hope that this discovery will open up the possibility of new ways to treat congenital disorders of the autonomous nervous system using regenerative medicine.
(Source: ki.se)
Brain cell find points to new therapies
Insights into how brain cells are produced could lead to treatments for brain cancer and other brain-related disorders.
Scientists have gained new understanding of the role played by a key molecule that controls how and when nerve and brain cells are formed - a process that allows the brain to develop and keeps it healthy.
Their findings could help explain what happens when cell production goes out of control, which is a fundamental characteristic of many diseases including cancer.
Regulatory systems
Researchers have focused on a RNA molecule, known as miR-9, which is linked to the development of brain cells, known as neurons and glial cells.
They have shown that a protein called Lin28a regulates the production of miR-9, which in turn controls the genes involved in brain cell development and function.
Scientists carried out lab studies of embryonic cells, which can develop into neurons, to determine how Lin28a controls the amount of miR-9 that is produced.
Complex pathways
They found that in embryonic cells, Lin28a prevents production of miR-9 by triggering the degradation of its precursor molecule.
In developed brain cells, Lin28a is no longer produced, which enables miR-9 to accumulate and function.
In cancer cells, Lin28a production is re-established, and as a result this natural process is disrupted.
Lab experiments
Researchers used a series of lab tests to unravel the complex processes that are directed by the Lin28a protein.
They say further studies could help explain fully the role of Lin28a and miR-9 in brain development, and pave the way to the development of novel therapies.
The study, published in Nature Communications, was supported by the Wellcome Trust and the Medical Research Council.
Understanding more of the complex science behind the fundamental processes of cell development will helps us learn more about what happens when this goes wrong – and what might be done to prevent it. -Dr Gracjan Michlewski (School of Biological Sciences)
(Image: iStock)
Anti-epilepsy drugs can cause inflammations
Glial cells play a crucial role in the nervous system
Hannes Dambach from the Department for Neuroanatomy and Molecular Brain Research, together with a team of colleagues, studied how anti-epilepsy drugs affect the survival of glial cells in cultures. Glial cells are the largest cell group in the brain; they are crucial for supplying neurons with nutrients and affect immune and inflammatory responses. The question of how glial cells are affected by anti-epilepsy drugs had previously not been studied in depth. The RUB work group Clinical Neuroanatomy, headed by Prof Dr Pedro Faustmann, analysed four substances: valproic acid, gabapentin, phenytoin and carbamazepine.
Four anti-epilepsy drugs affect glial cells in different ways
Glial cells treated by the researchers with valproic adic and gabapentin had better survival chances than those treated with phenytoin and carbamazepine. However, carbamazepine had a positive effect, too: it reduced inflammatory responses. Valproic acid, on the other hand, turned out to be pro-inflammatory. In how far the anti-epilepsy drugs affected inflammations was also determined by the applied dose. Consequently, different drugs affected glial cells – and hence indirectly the neurons – in different ways.
Inflammatory responses should be taken under consideration in clinical studies
“Clinical studies should focus not only on the question in how far anti-epilepsy drugs affect the severity and frequency of epileptic seizures,” says Pedro Faustmann. “It is also necessary to test them with regard to the role they play in inflammatory responses in the central nervous system.” Thus, doctors could take the underlying inflammatory condition under consideration when selecting the right anti-epilepsy drug.
Epilepsy may have different causes
In Germany, between 0.5 and 1 percent of the population suffer from epilepsy that requires drug treatment. The disease may have many causes: genetic predisposition, disorders of the central nervous system after meningitis, traumatic brain injury and stroke. Inflammatory responses may also be caused by damage to the brain.