Rabies causes acute inflammation of the brain, producing psychosis and violent aggression. The virus, which paralyzes the body's internal organs, is always deadly for those unable to obtain vaccines in time. Some 55,000 people die from rabies every year.
For the first time, Tel Aviv University scientists have discovered the exact mechanism this killer virus uses to efficiently enter the central nervous system, where it erupts in a toxic explosion of symptoms. The study, published in PLOS Pathogens, was conducted by Dr. Eran Perlson and Shani Gluska of TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience, in collaboration with the Friedrich Loeffler Institute in Germany.
"Rabies not only hijacks the nervous system's machinery, it also manipulates that machinery to move faster," said Dr. Perlson. "We have shown that rabies enters a neuron in the peripheral nervous system by binding to a nerve growth factor receptor, responsible for the health of neurons, called p75. The difference is that its transport is very fast, even faster than that of its endogenous ligand, the small molecules that travel regularly along the neuron and keep the neuron healthy."
Faster than a speeding train
To track the rabies virus in the nervous system, the researchers grew mouse sensory neurons in an observation chamber and used live cell imaging to track the path taken by the virus particles. The researchers "saw" the virus hijack the "train" transporting cell components along a neuron and drove it straight into the spinal cord. Once in the spinal cord, the virus caught the first available train to the brain, where it wrought havoc before speeding through the rest of the body, shutting it down organ by organ.
Nerve cells, or neurons, outside the central nervous system are highly asymmetric. A long protrusion called an axon extends from the cell body to another nerve cell or organ along a specific transmission route. In addition to rapid transmission of electric impulses, axons also transport molecular materials over these distances.
"Axonal transport is a delicate and crucial process for neuronal survival, and when disrupted it can lead to neurodegenerative diseases," said Dr. Perlson. "Understanding how an organism such as rabies manipulates this machinery may help us in the future to either restore the process or even to manipulate it to our own therapeutic needs."
Hijacking the hijacker
"A tempting premise is to use this same machinery to introduce drugs or genes into the nervous system," Dr. Perlson added. By shedding light on how the virus hijacks the transport system in nerve cells to reach its target organ with maximal speed and efficiency, the researchers hope their findings will allow scientists to control the neuronal transport machinery to treat rabies and other neurodegenerative diseases.
Disruptions of the neuron train system also contribute to neurodegenerative diseases, like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). According to Dr. Perlson, "An improved understanding of how the neuron train works could lead to new treatments for these disorders as well."
Explore further: From bite site to brain: How rabies virus hijacks and speeds up transport in nerve cells
Medical Xpress on facebook
Related Stories
From bite site to brain: How rabies virus hijacks and speeds up transport in nerve cells
Aug 28, 2014
Rabies (and rabies virus, its causative agent) is usually transmitted through the bite of an infected animal into muscle tissue of the new host. From there, the virus travels all the way to the brain where ...
Jefferson researchers' discovery may change thinking on how viruses invade the brain
Apr 19, 2007
A molecule thought crucial to ferrying the deadly rabies virus into the brain, where it eventually kills, apparently isn’t. The surprising finding, say researchers at Jefferson Medical College in Philadelphia, may change ...
Discovery of new pathways controlling the serotonergic system
Aug 08, 2014
With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific ...
Mouse model sheds light on role of mitochondria in neurodegenerative diseases
Sep 19, 2014
A new study by researchers at the University of Utah School of Medicine sheds light on a longstanding question about the role of mitochondria in debilitating and fatal motor neuron diseases and resulted in a new mouse model ...
Report documents organ transplantation as source of fatal rabies virus case
Jul 23, 2013
An investigation into the source of a fatal case of raccoon rabies virus exposure indicates the individual received the virus via a kidney transplant 18 months earlier, findings suggesting that rabies transmitted by this ...
Recommended for you
Oxycodone may be more dangerous than other addictive pain medication
10 minutes ago
While all prescription opioids can be abused, oxycodone may be more potent in its ability to promote changes in the brain relevant to addiction.
A glimpse into the 3D brain: How memories form
3 hours ago
People who wish to know how memory works are forced to take a glimpse into the brain. They can now do so without bloodshed: RUB researchers have developed a new method for creating 3D models of memory-relevant ...
Zapping the brain with tiny magnetic pulses improves memory
4 hours ago
The practice of physically stimulating the brain in order to alleviate symptoms of illness and injury has been around since the early 20th century. For example, electroconvulsive therapy (ECT) is still used ...
The spatial and temporal dynamics of specific glutamate receptors in the brain
5 hours ago
Dr. Uwe Schulte, Dr. Jochen Schwenk, Prof. Dr. Bernd Fakler, and their team have elucidated the enormous spatial and temporal dynamics in protein composition of the AMPA-type glutamate receptors, the most ...
Trio win Nobel medicine prize for brain's 'GPS' (Update)
6 hours ago
British-American researcher John O'Keefe on Monday won the Nobel Medicine Prize with a Norwegian couple, May-Britt and Edvard Moser, for discovering an "inner GPS" that helps the brain navigate.
Stroke researchers explore implications of ipsilateral spatial neglect after stroke
Oct 03, 2014
Stroke researchers have confirmed that damage to the right frontal-subcortical network may cause ipsilateral spatial neglect. Among individuals with ipsilateral neglect, a much greater proportion had frontal ...
User comments
© Medical Xpress 2011-2014, Science X network
Rabies causes acute inflammation of the brain, producing psychosis and violent aggression. The virus, which paralyzes the body's internal organs, is always deadly for those unable to obtain vaccines in time. Some 55,000 people die from rabies every year.
For the first time, Tel Aviv University scientists have discovered the exact mechanism this killer virus uses to efficiently enter the central nervous system, where it erupts in a toxic explosion of symptoms. The study, published in PLOS Pathogens, was conducted by Dr. Eran Perlson and Shani Gluska of TAU's Sackler Faculty of Medicine and Sagol School of Neuroscience, in collaboration with the Friedrich Loeffler Institute in Germany.
"Rabies not only hijacks the nervous system's machinery, it also manipulates that machinery to move faster," said Dr. Perlson. "We have shown that rabies enters a neuron in the peripheral nervous system by binding to a nerve growth factor receptor, responsible for the health of neurons, called p75. The difference is that its transport is very fast, even faster than that of its endogenous ligand, the small molecules that travel regularly along the neuron and keep the neuron healthy."
Faster than a speeding train
To track the rabies virus in the nervous system, the researchers grew mouse sensory neurons in an observation chamber and used live cell imaging to track the path taken by the virus particles. The researchers "saw" the virus hijack the "train" transporting cell components along a neuron and drove it straight into the spinal cord. Once in the spinal cord, the virus caught the first available train to the brain, where it wrought havoc before speeding through the rest of the body, shutting it down organ by organ.
Nerve cells, or neurons, outside the central nervous system are highly asymmetric. A long protrusion called an axon extends from the cell body to another nerve cell or organ along a specific transmission route. In addition to rapid transmission of electric impulses, axons also transport molecular materials over these distances.
"Axonal transport is a delicate and crucial process for neuronal survival, and when disrupted it can lead to neurodegenerative diseases," said Dr. Perlson. "Understanding how an organism such as rabies manipulates this machinery may help us in the future to either restore the process or even to manipulate it to our own therapeutic needs."
Hijacking the hijacker
"A tempting premise is to use this same machinery to introduce drugs or genes into the nervous system," Dr. Perlson added. By shedding light on how the virus hijacks the transport system in nerve cells to reach its target organ with maximal speed and efficiency, the researchers hope their findings will allow scientists to control the neuronal transport machinery to treat rabies and other neurodegenerative diseases.
Disruptions of the neuron train system also contribute to neurodegenerative diseases, like Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). According to Dr. Perlson, "An improved understanding of how the neuron train works could lead to new treatments for these disorders as well."
Explore further: From bite site to brain: How rabies virus hijacks and speeds up transport in nerve cells
Medical Xpress on facebook
Related Stories
From bite site to brain: How rabies virus hijacks and speeds up transport in nerve cells
Aug 28, 2014
Rabies (and rabies virus, its causative agent) is usually transmitted through the bite of an infected animal into muscle tissue of the new host. From there, the virus travels all the way to the brain where ...
Jefferson researchers' discovery may change thinking on how viruses invade the brain
Apr 19, 2007
A molecule thought crucial to ferrying the deadly rabies virus into the brain, where it eventually kills, apparently isn’t. The surprising finding, say researchers at Jefferson Medical College in Philadelphia, may change ...
Discovery of new pathways controlling the serotonergic system
Aug 08, 2014
With the aid of new methods, a research team at Karolinska Institutet have developed a detailed map of the networks of the brain that control the neurotransmitter serotonin. The study, published in the scientific ...
Mouse model sheds light on role of mitochondria in neurodegenerative diseases
Sep 19, 2014
A new study by researchers at the University of Utah School of Medicine sheds light on a longstanding question about the role of mitochondria in debilitating and fatal motor neuron diseases and resulted in a new mouse model ...
Report documents organ transplantation as source of fatal rabies virus case
Jul 23, 2013
An investigation into the source of a fatal case of raccoon rabies virus exposure indicates the individual received the virus via a kidney transplant 18 months earlier, findings suggesting that rabies transmitted by this ...
Recommended for you
Oxycodone may be more dangerous than other addictive pain medication
10 minutes ago
While all prescription opioids can be abused, oxycodone may be more potent in its ability to promote changes in the brain relevant to addiction.
A glimpse into the 3D brain: How memories form
3 hours ago
People who wish to know how memory works are forced to take a glimpse into the brain. They can now do so without bloodshed: RUB researchers have developed a new method for creating 3D models of memory-relevant ...
Zapping the brain with tiny magnetic pulses improves memory
4 hours ago
The practice of physically stimulating the brain in order to alleviate symptoms of illness and injury has been around since the early 20th century. For example, electroconvulsive therapy (ECT) is still used ...
The spatial and temporal dynamics of specific glutamate receptors in the brain
5 hours ago
Dr. Uwe Schulte, Dr. Jochen Schwenk, Prof. Dr. Bernd Fakler, and their team have elucidated the enormous spatial and temporal dynamics in protein composition of the AMPA-type glutamate receptors, the most ...
Trio win Nobel medicine prize for brain's 'GPS' (Update)
6 hours ago
British-American researcher John O'Keefe on Monday won the Nobel Medicine Prize with a Norwegian couple, May-Britt and Edvard Moser, for discovering an "inner GPS" that helps the brain navigate.
Stroke researchers explore implications of ipsilateral spatial neglect after stroke
Oct 03, 2014
Stroke researchers have confirmed that damage to the right frontal-subcortical network may cause ipsilateral spatial neglect. Among individuals with ipsilateral neglect, a much greater proportion had frontal ...
User comments
© Medical Xpress 2011-2014, Science X network
0 comments:
Post a Comment