Overlooked Cells Hold Keys to Brain Organization and Disease


May 1, 2014
Brain & Behavior

Scientists studying brain diseases may need to look beyond nerve cells and start paying attention to the star-shaped cells known as “astrocytes,” because they play specialized roles in the development and maintenance of nerve circuits and may contribute to a wide range of disorders, according to a new study by UC San Francisco researchers.

In a study published online April 28, 2014 in Nature, the researchers report that malfunctioning astrocytes might contribute to neurodegenerative disorders such as Lou Gehrig’s disease (ALS), and perhaps even to developmental disorders such as autism and schizophrenia.

David Rowitch, MD, PhD, UCSF professor of pediatrics and neurosurgery and a Howard Hughes Medical Institute investigator, led the research.

The researchers discovered in mice that a particular form of astrocyte within the spinal cord secretes a protein needed for survival of the nerve circuitry that controls reflexive movements. This discovery is the first demonstration that different types of astrocytes exist to support development and survival of distinct nerve circuits at specific locations within the central nervous system.

Astrocytes vastly outnumber signal-conducting neurons, and make up the majority of cells in the brain. But where neuroscientists are accustomed to seeing only vanilla when it comes to astrocytes – viewing all of them as similar despite their different locations in brain and spinal cord –they now will have to imagine “31 flavors” or more.

There might even be hundreds of distinctive varieties of astrocytes performing specific functions in different locations, according to Rowitch, chief of neonatology for UCSF Benioff Children’s Hospital San Francisco.

“Our study shows roles for specialized astrocytes that function to support particular kinds of neurons in their neighborhood,” Rowitch said.

Led by Rowitch lab postdoctoral fellow Anna Molofsky, MD, PhD, the researchers studied the spinal cord sensory motor circuit, which allows both mice and humans to react without thought – to jerk a limb away from something hot, for instance.

The team discovered that a protein called Sema3a is produced much more abundantly by astrocytes close to motor neurons than by astrocytes from other regions in the spinal cord.  They concluded that motor neurons required this source of Sema3a from the local astrocytes, because when Sema3a production was blocked, the motor neurons failed to form normal connections, and half of them died.

Motor neurons also die in ALS, a fatal neurodegenerative disease, and in spinal muscular atrophy, a disease that can affect newborn infants.  In other studies, scientists have found that abnormal astrocytes can have toxic effects on motor neurons.

Molofsky is a psychiatrist who studies how astrocytes organize nerve circuits, and how disruptions of these nerve circuits during development or disease may involve abnormal astrocyte function. Disrupted neural circuits are believed to be responsible for certain psychiatric disorders.

“The immediate implications of this study are for diseases of motor neurons, like ALS, but I think our findings might also apply more generally to diseases of neural-circuit formation in the brain such as autism, schizophrenia and epilepsy,” Molofsky said. “To achieve a comprehensive understanding of how neural circuits form and are maintained, it seems important that we integrate knowledge of how astrocytes support that process.”

Rowitch agrees. “To the extent that psychiatric or neurological disease is localized to a specific part of the brain, we should now be considering the potentially specialized type of astrocytes regulating nerve connections in that region and their contributions to disease,” he said.

The research was funded by the National Institute for Neurological Diseases and Stroke, the National Institute of Mental Health and the Howard Hughes Medical Institute.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes top-ranked graduate schools of dentistry, medicine, nursing and pharmacy, a graduate division with nationally renowned programs in basic biomedical, translational and population sciences, as well as a preeminent biomedical research enterprise and two top-ranked hospitals, UCSF Medical Center and UCSF Benioff Children’s Hospital San Francisco.



Overlooked Cells Hold Keys to Brain Organization and Disease

9 Responses to Overlooked Cells Hold Keys to Brain Organization and Disease

  1. Miche' May 3, 2014 at 2:47 pm #

    This research is really interesting. To think that there is a part of our brains that are overlooked and that have the potential to help solve many of the problems associated with the brain is amazing and scary at the same time. It shows that even the smallest part of a well oiled machine is important.

    These astrocytes seem to have great potential and such research is important in figuring out whether there are specific “things” in the brain that cause certain diseases, besides those that are already known. Astrocytes might ,even be the part of the brain that help us find out how the mind works and we can go further from there, and even discover more parts of the brain, and body, that could help us solve many more questions.

    By knowing that astrocytes play an important part in development and maintenance in nerve circuits, according to this research, is it possible that by more studies that astrocytes could find cures to many brain diseases such as autism, and even memory loss due to old age or Alzheimer’s disease?

  2. Lesego(13125622) May 3, 2014 at 3:11 am #

    Its interesting how overlooked cells of the brains happen to be the most vital cells that can cause brain disorders. I believe by the discoveries made it will be able to assist neurosurgeons detect many disorders they could not be able to solve way back then in the past, such as Schizophrenia and many other disorders. David Rowitch and the Howard Hughes medical institute investigator really did a great job about the discovery and the only thing that would be left is to research the termination of such disorders from occurring or rather the solution to the abnormality of these astrocytes.With the help of many other available and future scientists I believe we can be able to conquer this issue.

  3. Iwan Sipsma (14067511) May 2, 2014 at 11:13 am #

    This new research is for me very interesting and it makes me smile to know that there is still ongoing research everyday and that doctors aren’t sitting back but still researching the human body. With this new discovery who knows what may follow next? This now may seem small but this can improve the way the medical sciences think forever.
    Whilst just looking at this new discovery of the so called “astrocytes” which is a mile stone discovery, we can use this to take an even deeper look into the amazing human body and understand it better. Now that we know more of the central nervous system we can maybe understand why certain unknown factors happen to us as humans. We can use this to develop newer and better operations to almost cure the harsh sicknesses that’s among us.
    This is an astonishing discovery and it excites me for my further studies in the future.

  4. Lourens Koekemoer, u14039517 May 2, 2014 at 8:19 am #

    In consideration of this research, it becomes clear that these astrocytes are of fundamental importance in our lives. This expanding field of science provides more than just understanding of how the human brain works. It is a total reflection of the future cure for neuro-degenerative disorders. If it is possible to culture these cells in a lab to produce sufficient amounts of the Sema3a protein, then diseases associated with motor neurons would be a thing of the past. Seeing that Alzheimer is associated with neuron degeneration, it may be possible to identify an astrocyte that can produce specific proteins to maintain or form new connections between neurons to fight the disease.

    Even if it is not possible to cure these disorders, it could be used as a form of prevention, to ensure that neurons and neuron connections are stable in the future (providing immunity of some sort). Therefore, if these specific astrocytes function to maintain particular neurons in the central nervous system, disorders associated with these individual neurons could be overcome. This research is truly intriguing!

  5. Kwando Shabalala (u14125651) May 2, 2014 at 8:15 am #

    WLRIIMjFQT04

  6. 14247594 May 2, 2014 at 4:47 am #

    The astrocytes provide neurons with some of the chemicals needed for proper functioning and help control the chemical composition of fluid surrounding neurons.So if there could be more clearity on how they can cause cancer.There also need a research to be conducted how these astrocytes can be preserved to perform their tusk and not be a health hazard at a later stage in life.

  7. 13120094 May 2, 2014 at 3:47 am #

    This scientific article is very interesting,it tells us the most important part of the central nervous system which is responsible for the movement and production of proteins that can be used in the reflect action of the central nervous system,this part is called an astrocyte,and it is very important to also know that it produces the protein that can be used by motor neurons during signal transmission.the article also explain the negative effects of exccess production of proteins by astrocyte and the insufficient production of hormones by this particular part .there i have learned that this astrocyte must be in balance because if it is in excess it can cause disease and when it is insufficient it can also lead to disease.
    from the article i also find that the astrocyte is also found in may different parts of brain.
    This article is benefitable because it explains the importance of astrocytes and also explains the negative impacts o abnormal astrocyte cells,which lead us to the conclusion that this cells must be in balance in order to promote normal functioning of central nervous system and a reflex action.

  8. 14003008 May 2, 2014 at 3:39 am #

    The research for factors that contribute to certain neurological disorders is exponentially expanding, astrocytes can provide crucial information that could lead to cures for such diseases and also to understand how the brain truly functions. The numerous astrocytes as describes in the article make up the majority of the cells in the brain and by understanding how they function, we can somehow find out how they influence signal-conducting neurons such as motor and sensory neurons.

  9. 14068720 May 2, 2014 at 1:18 am #

    This discovery is something I have never heard of before. These ”astrocytes” seem to play a great role in the functioning of the nervous system. If we can conduct further studies on how they work and the implications they might have on the body as a whole, we might discover a lot more cures to diseases associated with the nervous system. Who knows, maybe one day we might even be able to enhance normal reaction time and muscular functioning to an almost “superhuman” ability.

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