DAYTON, Ohio, Oct. 24 (AScribe Newswire) -- Wright State
University announced today that is has received a
prestigious Program Project Grant (PPG) from the National
Institute of Neurological Disorders and Stroke (NINDS). The
$4.8 million grant is the first Program Project Grant Wright
State University has received. Five university scientists
will use the grant to further their research into why full
recovery is not always achieved after damaged nerves have
regenerated.
"These grants are extremely competitive, and this award underscores
the high caliber of neuroscience research being conducted at Wright
State," said David R. Hopkins, president of Wright State. "In this
research arena we are successfully competing at a national level. We
are extremely proud that Wright State has taken a leadership role by
bringing this Program Project Grant to the region."
Program Project Grants are designed to "encourage multidisciplinary
research approaches to a diverse array of nervous system disorders,"
according to NINDS, one of the 27 institutes and centers that
comprise the National Institutes of Health, and the guidelines
require at least three interrelated projects that contribute to the
program objective. Five collaborative projects, each led by a Wright
State NIH-funded investigator, will work together to better
understand the recovery - or lack of it - from neurotrauma.
The team of Wright State investigators - Drs. Francisco Alvarez,
Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich - are
accomplished researchers in fields covering developmental biology,
synaptic function and sensorimotor behavior of the spinal cord and
Peripheral nervous system. The diversity of their analytical
viewpoints will, through this grant, create a synergy of research
information focused on a common interest. (see sidebar on the five
projects)
When the Connections No Longer Work: Nerve Regeneration
Our wired communication system sends and receives electrical impulses
from the Central Nervous System (CNS) through a highly specialized
Peripheral Nervous System (PNS), which transmits sensory information
and controls movement. The PNS relays messages from the body to the
brain and regulates internal processes. When the PNS is damaged,
nerve activity may be blocked, interrupted or completely disrupted,
depending on the severity of the injury.
Damage to the PNS, peripheral neuropathy, includes more than 100
classifications, each unique in its presenting symptoms, based upon
the type of nerves damaged - Motor, sensory, or autonomic, or a
combination of these. The most common cause of peripheral neuropathy
is trauma. But, chemotherapy and a wide range of systemic diseases,
including diabetes mellitus, vascular disease, and kidney disorders,
also damage nerves and neuronal cells. Unlike the CNS, the PNS can
regenerate both neurons and nerve circuitry.
"We know that damaged peripheral nerves regenerate, but regeneration
is not synonymous with recovery," said Timothy Cope, Ph.D., professor
and chair of the Department of Neuroscience, Cell Biology, and
Physiology in WSU's Boonshoft School of Medicine, director of the
school's new Comprehensive Neuroscience Center, and principal
investigator on the PPG. "Neither sensation nor movement return to
pre-injury levels after nerve regeneration. Although regeneration of
the PNS is necessary to restore voluntary movement, injury initiates
changes in the spinal cord that do not reverse with regeneration.
Problems remain in timing and strength of muscle contraction,
problems that are essential to normal movement."
The goal of Wright State's Program Project Grant is "to understand
how injury, regeneration and alterations in neural activity affect
synaptic and network function and to explore the mechanisms that
either promote or impede recovery," said Cope. "The wide array of
approaches and expertise that we have as a team is likely to
accelerate our understanding because we can attack the problem of
limits on regeneration with greater insight and technical expertise
than any one of us could achieve alone."
Cutting-edge methodologies will be shared across the five projects.
Studies will examine neurons and synapses using electrophysiological
tools to evaluate their function. Microscopy and associated imaging
techniques will assess structure and changes in protein expression.
"Collaboration with the other team members is critical to placing our
findings in the context of Functional and structural changes that are
occurring in the CNS and PNS after nerves regenerate," adds Dr.
Fyffe, Ph.D., associate dean for research affairs.
"Essential details about the mechanisms underlying changes following
PNS injury are largely unknown and must be obtained in order to
develop clinical applications to many common human conditions,
including spinal cord injury," adds Dr. Cope. "How can we get these
neural circuits to operate normally, to communicate the way they used
to? Our research niche focuses on the limits to recovery after nerve
regeneration."
Affirming our goals, our resources and our expertise
"Getting this grant places us in an elite category," says Howard M.
Part, M.D., dean for the Boonshoft School of Medicine. "Our team's
impressive accomplishment reflects the hard work and dedication of
our outstanding scientists, as well as the continued support of our
community, especially from The Kettering Fund and from the Oscar
Boonshoft family."
Grants received from these sources helped coordinate neuroscience
research and recruit additional outstanding research faculty to
Wright State. The Kettering Fund has supported biomedical research at
the Boonshoft School of Medicine since 1998 and was instrumental in
advancing several key research areas at the medical school.
In February, the school announced the formation of a Comprehensive
Neuroscience Center (CNC) for improving research of neurological,
developmental, cognitive, psychiatric and trauma-induced nervous
system disorders. The CNC was made possible through a grant from the
Boonshoft Innovation Fund, established when Oscar Boonshoft, a local
philanthropist and long-time supporter, gave Wright State University
School of Medicine a gift of $28.5 million dollars in 2005. His goal
was to provide new resources to spur innovative ideas and programs
that would propel the school to national leadership in medical
education, patient care and research.
The newly established center integrates teams of scientists and
clinicians across several disciplines - on and off campus - to
collaboratively address fundamental issues in both basic science and
clinical neuroscience research. Actively involved are faculty in the
fields of biochemistry, cell biology, molecular biology,
neuroscience, pharmacology, physiology, psychiatry, psychology and
toxicology.
"The CNC will advance our research of the nervous system at levels
ranging from cellular and molecular mechanisms to behavior," said Cope.
"The Program Project Grant has, in effect, affirmed our goals, our
resources and our expertise. The vision for this collaborative center
is to continue to build upon our core strengths and infrastructure as
well as leverage strategic resources," said Part. "We see
neuroscience research as a significant growth area and an important
component in educating our students and advancing patient care."
The five interrelated projects
Detailed scientific information available at med.wright.edu/cnc/ppg
The Program Project Grant recently awarded to five Wright State
University researchers by the National Institute of Neurological
Disorders and Stroke reaffirms that there is strength in numbers in
scientific endeavors. It is the power of shared experience, shared
expertise, technology, equipment and resources that are at the
foundation of a Program Project Grant. Drs. Francisco Alvarez,
Timothy Cope, Kathrin Engisch, Robert Fyffe and Mark Rich bring
decades of combined expertise to the pursuit of their common
interest. Following are specifics about the researchers' five
individual projects by which they endeavor to better understand the
recovery - or lack of it - from neurotrauma.
Project One: Circuit Plasticity
Timothy Cope, Ph.D.
Professor and Chair of Neuroscience, Cell Biology and Physiology
Director, Comprehensive Neuroscience Center
Program Project Grant principal investigator
"After nerve damage and regeneration, we lose the stretch Reflex in
affected muscles, adversely affecting our ability to control
movement. We theorize that damage to the PNS creates problems in
spinal/neural circuits which do not reverse after nerve regeneration."
Project Two: Excitatory/Inhibitory Balance
Francisco J. Alvarez, Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
Director of Imaging Core Facilities
"Motoneurons control the activity in our muscles, but their function
is in turn modulated by a fine balance between excitatory and
inhibitory influences. We suspect that deficits in reacquiring this
balance following nerve injury and regeneration are partly
responsible for the incomplete restoration of motor function."
Project Three: Synaptic Plasticity
Mark Rich, M.D., Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
"Injury changes how the synapses transmit at the neuromuscular
junction and we theorize that reduced cellular activity at the time
of injury adversely impacts signaling strength."
Project Four: Molecular Regulation of Release
Kathrin Engisch, Ph.D.
Associate Professor of Neuroscience, Cell Biology and Physiology
"We are examining the underlying molecular mechanism caused by the
change of cellular activity. The process at the molecular level
indicates that the protein Rab3A plays a major regulatory role."
Project Five: Postsynaptic Excitability
Robert E. W. Fyffe, Ph.D.
Associate Dean for Research Affairs
"Our laboratory will use new imaging techniques to help determine how
the excitability and electrical properties of motoneurons are
regulated after nerve injury."
For more information or to arrange for interviews, please contact
Judi Engle, Director of Strategic Communications and Public
Relations, Wright State University Boonshoft School of Medicine,
937-775-2951 or judith.engle@wright.edu.