gpbullock
08-14-2001, 09:48 AM
EMBARGOED FOR RELEASE
Sunday, July 1, 2001
12:01 a.m. EST
Contact:
Natalie Frazin
301-496-5751
Manipulating A Single Gene Dramatically Improves Regeneration in Adult Neurons
Finding May Lead to New Approaches for Treating Brain and Spinal Cord Damage
Increasing the expression of a single gene that is important during development dramatically improves the ability of adult neurons to regenerate, a new study shows.
The finding suggests that intrinsic properties of neurons play an important role in controlling neuronal regeneration and may lead to new approaches for treating
damage from stroke, spinal cord injury, and other neurological conditions.
The study examined how genetically engineering adult neurons to produce larger amounts of a type of protein called integrin affects nerve fiber growth. This
approach is one of the first to examine "the critical missing half of the regeneration equation: the properties of adult neurons, rather than the environment of the adult
brain," says study investigator Maureen L. Condic, Ph.D., of the University of Utah School of Medicine in Salt Lake City. The work was supported by the National
Institute of Neurological Disorders and Stroke (NINDS) and will appear in the July 1, 2001, issue of the Journal of Neuroscience1.
Most neural regeneration studies in the past have manipulated factors in the environment of the adult nervous system to try to influence neuron growth. Studies have
shown that nerve fibers can regenerate in the brain and spinal cord of newborn animals, but regeneration does not normally occur in the brain or spinal cord of older
animals. Recent studies have linked neuronal regeneration to integrin proteins, which function as receptors that enable neurons to interact with specialized molecules
in the surrounding environment during development. Neurons taken from developing animals typically have very high levels of integrin, but neurons from adult animals
have very little of this protein.
In this study, Dr. Condic used a modified adenovirus to insert extra copies of a gene for one kind of integrin protein into sensory neurons taken from adult rats. A
second group of neurons received extra copies of a different integrin gene. The additional genes produced levels of integrin in the adult neurons that were
comparable to those in newborn animals. The neurons were cultured in conditions similar to those of the adult central nervous system. Dr. Condic then measured the
amount of nerve fiber growth displayed by the adult neurons with extra integrin genes and compared it to the growth of neurons from newborn rats and of adult
neurons that had received a non-integrin gene. She found that increasing the amount of either of the integrin proteins dramatically increased the amount of nerve fiber
growth in the adult neurons. The increase in growth was more than ten times greater than that in any other published study of regeneration by adult neurons. The
adult neurons with the extra integrin genes were able to extend nerve fibers profusely even when growth-inhibiting proteins were present in the culture. The amount of
growth was indistinguishable from that of neurons from newborn animals.
The magnitude of the integrin proteins' effects on the adult neurons was very surprising, Dr. Condic says. In the past, many scientists believed that the inherent
limitations on growth of nerve fibers from adult neurons were too complex to be significantly affected by altering a few genes. In this study, however, the effect of
increasing just one gene was striking. "It's as though you have a '57 Chevy on blocks in the front yard, and it has all the necessary components except for its wheels,"
says Dr. Condic. "If you give the wheels back, which are the car's usual way of interacting with the environment, it's ready to go." Integrin proteins are like the tires
of the car - they connect with the surrounding surface to enable neurons to extend nerve fibers, she explains.
The finding complements studies of factors in the nervous system environment that improve regeneration. Effective therapies will probably employ a multi-pronged
approach that alters environmental factors as well as the inherent properties of the neurons, Dr. Condic says. However, it should be much easier to regulate gene
expression in specific neurons than to change the environment of the brain. "The nervous system is a very big place, and right now we don't have the technology to
modulate the total environment of the brain," Dr. Condic explains. Because the nervous system is so complex, there is also a risk that changes to the environment of
the brain could inadvertently harm neurons outside of the damaged area and result in problems such as epilepsy or increased sensitivity to pain.
It may eventually be possible to modify integrin genes with a type of "switch" that is controlled by drugs or other chemicals and inject those genes into a damaged
area of the brain, says Dr. Condic. Doctors could then add and subtract the chemical to turn the genes on and off, allowing them to precisely control the amount of
nerve fiber growth in that region of the brain. However, an approach of this type is still theoretical, and more research is needed before scientists can predict whether
such a technique might work in humans.
Dr. Condic and colleagues are now planning to study integrin gene expression in an animal model with a type of spinal cord injury that is common in humans. "This is
the next critical step," she says. "At this point, all systems look 'go' with blazing green lights - but in animals, it's much more complicated."
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous
system. The NINDS is now celebrating its 50th anniversary.
University of Utah Public Relations: Lee Siegel, ph: (801) 581-8993.
This release will be posted on EurekAlert! at http://www.eurekalert.org and on the NINDS website at http://www.ninds.nih.gov/news_and_events/index.htm.
1.Condic, M. L. "Adult Neuronal Regeneration Induced by Transgenic Integrin Expression." Journal of Neuroscience, Vol. 21, No. 13, July 1, 2001, pp.
4782-4788
Sunday, July 1, 2001
12:01 a.m. EST
Contact:
Natalie Frazin
301-496-5751
Manipulating A Single Gene Dramatically Improves Regeneration in Adult Neurons
Finding May Lead to New Approaches for Treating Brain and Spinal Cord Damage
Increasing the expression of a single gene that is important during development dramatically improves the ability of adult neurons to regenerate, a new study shows.
The finding suggests that intrinsic properties of neurons play an important role in controlling neuronal regeneration and may lead to new approaches for treating
damage from stroke, spinal cord injury, and other neurological conditions.
The study examined how genetically engineering adult neurons to produce larger amounts of a type of protein called integrin affects nerve fiber growth. This
approach is one of the first to examine "the critical missing half of the regeneration equation: the properties of adult neurons, rather than the environment of the adult
brain," says study investigator Maureen L. Condic, Ph.D., of the University of Utah School of Medicine in Salt Lake City. The work was supported by the National
Institute of Neurological Disorders and Stroke (NINDS) and will appear in the July 1, 2001, issue of the Journal of Neuroscience1.
Most neural regeneration studies in the past have manipulated factors in the environment of the adult nervous system to try to influence neuron growth. Studies have
shown that nerve fibers can regenerate in the brain and spinal cord of newborn animals, but regeneration does not normally occur in the brain or spinal cord of older
animals. Recent studies have linked neuronal regeneration to integrin proteins, which function as receptors that enable neurons to interact with specialized molecules
in the surrounding environment during development. Neurons taken from developing animals typically have very high levels of integrin, but neurons from adult animals
have very little of this protein.
In this study, Dr. Condic used a modified adenovirus to insert extra copies of a gene for one kind of integrin protein into sensory neurons taken from adult rats. A
second group of neurons received extra copies of a different integrin gene. The additional genes produced levels of integrin in the adult neurons that were
comparable to those in newborn animals. The neurons were cultured in conditions similar to those of the adult central nervous system. Dr. Condic then measured the
amount of nerve fiber growth displayed by the adult neurons with extra integrin genes and compared it to the growth of neurons from newborn rats and of adult
neurons that had received a non-integrin gene. She found that increasing the amount of either of the integrin proteins dramatically increased the amount of nerve fiber
growth in the adult neurons. The increase in growth was more than ten times greater than that in any other published study of regeneration by adult neurons. The
adult neurons with the extra integrin genes were able to extend nerve fibers profusely even when growth-inhibiting proteins were present in the culture. The amount of
growth was indistinguishable from that of neurons from newborn animals.
The magnitude of the integrin proteins' effects on the adult neurons was very surprising, Dr. Condic says. In the past, many scientists believed that the inherent
limitations on growth of nerve fibers from adult neurons were too complex to be significantly affected by altering a few genes. In this study, however, the effect of
increasing just one gene was striking. "It's as though you have a '57 Chevy on blocks in the front yard, and it has all the necessary components except for its wheels,"
says Dr. Condic. "If you give the wheels back, which are the car's usual way of interacting with the environment, it's ready to go." Integrin proteins are like the tires
of the car - they connect with the surrounding surface to enable neurons to extend nerve fibers, she explains.
The finding complements studies of factors in the nervous system environment that improve regeneration. Effective therapies will probably employ a multi-pronged
approach that alters environmental factors as well as the inherent properties of the neurons, Dr. Condic says. However, it should be much easier to regulate gene
expression in specific neurons than to change the environment of the brain. "The nervous system is a very big place, and right now we don't have the technology to
modulate the total environment of the brain," Dr. Condic explains. Because the nervous system is so complex, there is also a risk that changes to the environment of
the brain could inadvertently harm neurons outside of the damaged area and result in problems such as epilepsy or increased sensitivity to pain.
It may eventually be possible to modify integrin genes with a type of "switch" that is controlled by drugs or other chemicals and inject those genes into a damaged
area of the brain, says Dr. Condic. Doctors could then add and subtract the chemical to turn the genes on and off, allowing them to precisely control the amount of
nerve fiber growth in that region of the brain. However, an approach of this type is still theoretical, and more research is needed before scientists can predict whether
such a technique might work in humans.
Dr. Condic and colleagues are now planning to study integrin gene expression in an animal model with a type of spinal cord injury that is common in humans. "This is
the next critical step," she says. "At this point, all systems look 'go' with blazing green lights - but in animals, it's much more complicated."
The NINDS, part of the National Institutes of Health in Bethesda, Maryland, is the nation's leading supporter of research on the brain and nervous
system. The NINDS is now celebrating its 50th anniversary.
University of Utah Public Relations: Lee Siegel, ph: (801) 581-8993.
This release will be posted on EurekAlert! at http://www.eurekalert.org and on the NINDS website at http://www.ninds.nih.gov/news_and_events/index.htm.
1.Condic, M. L. "Adult Neuronal Regeneration Induced by Transgenic Integrin Expression." Journal of Neuroscience, Vol. 21, No. 13, July 1, 2001, pp.
4782-4788