Molecular body guards for neuronsMarch 02, 2016
In the brain, patterns of neural activity are perfectly balanced. The interplay between activating and inhibitory neurotransmitters ensures that the level of activity stays within the physiological range. During an epileptic attack excitation gains the upper hand resulting in the death of neurons. Researchers of the Bonn University Medical School have now discovered a key player in a signal transduction cascade, which protects neurons from hyperexcitation-induced cell death. These results open a new direction for the development of novel therapy options. The results are now published in „The Journal of Neuroscience".
Pathophysiological activity often triggers neuronal cell death. This can for example be observed after an epileptic insult. The cause for this hyperexcitation is excessive release of the signaling molecule glutamate. "This neurotransmitter can switch on signaling cascades that act neurotoxic", says Prof. Dr. Schoch McGovern of the Institute of Neuropathology and the Department of Epileptology at the University Clinic Bonn. However, neurons try to protect themselves and prevent the damaging hyperexcitation.
The molecular nature of these "body guards" is so far unresolved. Accumulating evidence shows transcription factors to play an essential role in the processes by which neurons protect themselves. These factors switch on certain genes, which then via signal transduction cascades result in the production of neuroprotective substances. These in turn counteract the damaging glutamate-induced hyperexcitability.
Increased neuronal cell death in the absence of Syt10
The team of Prof. Dr. Schoch McGovern could now show that the protein Synaptotagmin 10 (Syt10) is an integral part of this protective shield. If rats for example experience an epileptic seizure, the amount of Syt10 in the hippocampal formation of the brain strongly increases. The researchers used neurons from mice, in which the Syt10 gene had been ablated, and stimulated them with a glutamate like substance. This treatment resulted in substantial neuronal death.
NPAS4 modulates the production of protective factors
The research team discovered, which transcription factor activates the gene for Syt10 in response to pathophysiological neuronal activity. This essential member of the neuronal body guard is called NPAS4. The researchers cultured rodent neurons and added several transcription factors. NPAS4 activated the Syt10 gene and required Syt10 to exert its neuroprotective function. "NPAS4 triggers a signaling cascade that results in the production of neuroprotective factors", says Prof. Dr. Schoch McGovern.
Search for novel therapy approaches
The molecular identity of the neuroprotective substances is still unknown. "A potential candidate, the insulin-like growth factor IGF-1, was not able to reverse the increased neuronal cell death in the absence of Syt10", reports the neurobiologist. The next step therefore is to test other substances. Once the identity of the neuroprotective body guards is revealed, novel avenues for therapy development open up, for example for stroke and epilepsy patients. "The goal would be to administer these protective substances from the outside in order to prevent neuronal cell death in the brain", says Prof. Dr. Albert Becker, a medical doctor, who was part of the study. However, there is still a long road ahead.
University of Bonn
Related Neurons Articles:
One of the big challenges in the Neuroscience field is to understand how connections and communications trigger our behavior.
In a new study published in Neuron, investigators report on a transcription factor that they have found that can help certain neurons regenerate, while simultaneously killing others.
When many individual neurons collect data, how do they reach a unanimous decision?
Individual neurons can learn not only single responses to a particular signal, but also a series of reactions at precisely timed intervals.
Putting a turbo engine into an old car gives it an entirely new life -- suddenly it can go further, faster.
Turning the theory of how the human brain perceives time on its head, a novel analysis in mice reveals that dopamine neuron activity plays a key role in judgment of time, slowing down the internal clock.
Researchers have identified a large population of previously unrecognized young neurons that migrate in the human brain during the first few months of life, contributing to the expansion of the frontal lobe, a region important for social behavior and executive function.
For decades, scientists have struggled to develop a comprehensive census of cell types in the brain.
In the brain, patterns of neural activity are perfectly balanced.
University of Alberta researchers have developed a method of connecting neurons, using ultrashort laser pulses -- a breakthrough technique that opens the door to new medical research and treatment opportunities.
Related Neurons Reading:
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The Fourth Edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The book begins with properties of the many newly discovered ion channels that have emerged through mapping of the genome. These channels shape the way a single neuron generates varied patterns of electrical activity. Covered next are the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The following section examines the biochemical pathways that are linked to the action of... View Details
The Neuron: Cell and Molecular Biology
by Irwin B. Levitan (Author), Leonard K. Kaczmarek (Author)
The third edition of The Neuron provides a comprehensive first course in the cell and molecular biology of nerve cells. The first part of the book covers the properties of the many ion channels that shape the way a single neuron generates varied patterns of electrical activity, as well as the molecular mechanisms that convert electrical activity into the secretion of neurotransmitter hormones at synaptic junctions between neurons. The second part covers the biochemical pathways that are linked to the action of neurotransmitters and can alter the cellular properties of neurons or... View Details
The 7 Secrets of Neuron Leadership: What Top Military Commanders, Neuroscientists, and the Ancient Greeks Teach Us about Inspiring Teams
by W. Craig Reed (Author), Gordon R. England (Foreword)
Leadership techniques backed by the world's most effective teams
The 7 Secrets of Neuron Leadership offers a diverse collection of wisdom and practical knowledge to help you build and lead your most effective team yet. Written by a former U.S. Navy diver, this book draws from the author's experiences and beyond to reveal key truths about the nature of teamwork, and expose the core of effective team leadership. You'll go back to ancient Greece to discover the nine personality types and the seven types of love that form the foundation of human interaction, and learn how... View Details
Molecular and Cellular Physiology of Neurons, Second Edition
by Gordon L. Fain (Author), Margery J. Fain (Illustrator), Thomas O'Dell (Illustrator)
Molecular and Cellular Physiology of Neurons, Second Edition is a comprehensive, up-to-date introduction to essential concepts of cellular neuroscience. Emphasizing experimental approaches and recent discoveries, it provides an in-depth look at the structure and function of nerve cells, from protein receptors and synapses to the biochemical processes that drive the mammalian nervous system.
Starting with the basics of electrical current flow across cell membranes, Gordon Fain covers voltage gating and receptor activation in the context of... View Details
From Neurons to Neighborhoods : The Science of Early Childhood Development
by Committee on Integrating the Science of Early Childhood Development (Author), Youth, and Families Board on Children (Author), National Research Council (Author), Committee on Integrating the Science of Early Childhood Development (Author), Jack P. Shonkoff (Editor), Deborah A. Phillips (Editor)
How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media.
How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a... View Details
From Neuron to Brain
by John G. Nicholls (Author), A. Robert Martin (Author), David A. Brown (Author), Mathew E. Diamond (Author), David A. Weisblat (Author), Paul A. Fuchs (Author)
From Neuron to Brain, Fifth Edition, provides a readable, up-to-date book for use in undergraduate, graduate, and medical school courses in neuroscience. As in previous editions, the emphasis is on experiments made by electrical recordings, molecular and cellular biological techniques, and behavioral studies on the nervous system, from simple reflexes to cognitive functions. Lines of research are followed from the inception of an idea to new findings being made in laboratories and clinics today.
A major change is that this edition begins with the anatomy and physiology of the... View Details
From Photon to Neuron: Light, Imaging, Vision
by Philip Nelson (Author)
A richly illustrated undergraduate textbook on the physics and biology of light
Students in the physical and life sciences, and in engineering, need to know about the physics and biology of light. Recently, it has become increasingly clear that an understanding of the quantum nature of light is essential, both for the latest imaging technologies and to advance our knowledge of fundamental life processes, such as photosynthesis and human vision. From Photon to Neuron provides undergraduates with an accessible introduction to the physics of light and offers a unified view... View Details
Neuron: A Tutorial Study Guide
by Nicoladie Tam, Ph.D.
“Neuron” is a part of the college-level Principles of Biology course series and the Neuropsychopharmacology course series textbooks. It is a tutorial written in questions and answers format to describe the anatomy and physiology of the neurons in the brain.
It is a study guide with in-depth explanations. Each section is a modular unit that is self-contained for easy reading. The principles and concepts are introduced systematically so students can learn and retain the materials intuitively.
The Myth of Mirror Neurons: The Real Neuroscience of Communication and Cognition
by Gregory Hickok (Author)
An essential reconsideration of one of the most far-reaching theories in modern neuroscience and psychology.In 1992, a group of neuroscientists from Parma, Italy, reported a new class of brain cells discovered in the motor cortex of the macaque monkey. These cells, later dubbed mirror neurons, responded equally well during the monkey’s own motor actions, such as grabbing an object, and while the monkey watched someone else perform similar motor actions. Researchers speculated that the neurons allowed the monkey to understand others by simulating their actions in its... View Details
From Neuron to Brain: A Cellular and Molecular Approach to the Function of the Nervous System, Fourth Edition
by John G. Nicholls (Author), A. Robert Martin (Author), Bruce G. Wallace (Author), Paul A. Fuchs (Author)
In the 25 years since From Neuron to Brain was first published, the authors' aim has remained constant—to describe how nerve cells go about their business of transmitting signals, how the signals are put together, and how, out of this integration, higher functions emerge. The new Fourth Edition, while maintaining this focus, has been completely reformatted and updated.
The emphasis, as before, is on experiments, and on the way they are carried out. Using a narrative approach, the authors follow a line from the original inception of a new idea to an account of research being done today.... View Details