Overlooked cells hold keys to brain organization and disease

April 28, 2014

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 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 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 , and in , 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 are believed to be responsible for certain psychiatric disorders.

"The immediate implications of this study are for diseases of , 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.

Explore further: Study identifies key player in motor neuron death in Lou Gehrig's disease

More information: Astrocyte-encoded positional cues maintain sensorimotor circuit integrity, DOI: 10.1038/nature13161

Related Stories

Study identifies key player in motor neuron death in Lou Gehrig's disease

March 26, 2014
Amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, is marked by a cascade of cellular and inflammatory events that weakens and kills vital motor neurons in the brain and spinal cord. The process is complex, ...

Toxin from brain cells triggers neuron loss in human ALS model

February 6, 2014
In most cases of amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease, a toxin released by cells that normally nurture neurons in the brain and spinal cord can trigger loss of the nerve cells affected in the disease, ...

Huntington's disease: Study discovers potassium boost improves walking in mouse model

March 30, 2014
Tweaking a specific cell type's ability to absorb potassium in the brain improved walking and prolonged survival in a mouse model of Huntington's disease, reports a UCLA study published March 30 in the online edition of Nature ...

Researchers generate new neurons in brains, spinal cords of living adult mammals

February 25, 2014
UT Southwestern Medical Center researchers created new nerve cells in the brains and spinal cords of living mammals without the need for stem cell transplants to replenish lost cells.

Eavesdropping on brain cell chatter: Novel tools learn how astrocytes listen in on neurons

April 16, 2014
Everything we do—all of our movements, thoughts and feelings – are the result of neurons talking with one another, and recent studies have suggested that some of the conversations might not be all that private. Brain ...

Recommended for you

CRISPR sheds light on rare pediatric bone marrow failure syndrome

July 27, 2017
Using the gene editing technology CRISPR, scientists have shed light on a rare, sometimes fatal syndrome that causes children to gradually lose the ability to manufacture vital blood cells.

Study finds harmful protein on acid triggers a life-threatening disease

July 27, 2017
Using an array of modern biochemical and structural biology techniques, researchers from Boston University School of Medicine (BUSM) have begun to unravel the mystery of how acidity influences a small protein called serum ...

Post-stroke patients reach terra firma with new exosuit technology

July 26, 2017
Upright walking on two legs is a defining trait in humans, enabling them to move very efficiently throughout their environment. This can all change in the blink of an eye when a stroke occurs. In about 80% of patients post-stroke, ...

Molecular hitchhiker on human protein signals tumors to self-destruct

July 24, 2017
Powerful molecules can hitch rides on a plentiful human protein and signal tumors to self-destruct, a team of Vanderbilt University engineers found.

Researchers develop new method to generate human antibodies

July 24, 2017
An international team of scientists has developed a method to rapidly produce specific human antibodies in the laboratory. The technique, which will be described in a paper to be published July 24 in The Journal of Experimental ...

New vaccine production could improve flu shot accuracy

July 24, 2017
A new way of producing the seasonal flu vaccine could speed up the process and provide better protection against infection.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.