When the Connections No Longer Work: Nerve Regeneration -- Prestigious $4.8 Mill

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When the Connections No Longer Work: Nerve Regeneration --

Prestigious $4.8 Million Grant Advances Neuroscience Research at

State University

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DAYTON, Ohio, Oct. 24 (AScribe Newswire) -- 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 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 State, " said R. Hopkins, president of

State. " In this research arena we are successfully competing

at a national level. We are extremely proud that 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 State NIH-funded investigator, will work

together to better understand the recovery - or lack of it - from

neurotrauma.

The team of State investigators - Drs. Francisco

Alvarez, Cope, Kathrin Engisch, 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 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 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

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 Boonshoft family. "

Grants received from these sources helped coordinate

neuroscience research and recruit additional outstanding research

faculty to 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

Boonshoft, a local philanthropist and long-time supporter, gave

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

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, Cope, Kathrin Engisch, 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

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

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. "