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IGF-1 stimulates Corticospinal
Motor Neurons
ScienceDaily
November 4, 2006
In a new scientific study, a growth factor known
as Insulin-like Growth Factor 1 (IGF) has been shown to encourage the
rapid growth of corticospinal motor neurons (CSMN). These neurons are
vitally important because they connect the brain to the spinal cord,
allowing the brain to interact and send signals throughout the body.
Although these neurons are necessary for the brain to control the
human body, these cells are highly susceptible diseases such as Lou
Gehrigs disease, also known as amyotrophic lateral sclerosis.
What is ALS?
ALS is a disease in which the neurons in the
corticospinal region of the brain and spinal cord atrophy and die.
Over time, this leads to muscle tissue breakdown and neurological
misfires by the brain. The muscles twitch as a result of incomplete
connections. Eventually, ALS leads to a total breakdown of these
neuron passage ways which inevitably completely paralyze the arms and
legs and eventually the torso as well. ALS becomes ultimately fatal
as the chest muscles lose contact and the patient is no longer able
to breathe on his or her own. Strangely, ALS only effects motor
movement, and has no effect on the brain or perception, although the
effects on the body prove fatal over time.
IGF-1 Catalyses Axon Growth
In a recent publication of Nature Neuroscience, 2
researchers stationed at the Harvard Stem Cell Institute and the
Massachusetts General Hospital have developed an accurate description
of how IGF-1 leads to significant growth increases in the axons of
corticospinal motor neurons in in vitro testing. Axons are long, thin
strands that protrude from neurons, connecting them to other cells
and allowing them to send messages via electrical signal. When these
axons atrophy, it reduces the ability of neurons to connect with one
another and form sufficient circuits in order to efficiently deliver
messages.
The Devastating Effects of CSMN Atrophy
Although in vitro testing is a long way from
applicable medical theory, it is proof of concept and shows how vital
IGF-1 is to the human body and how future medical breakthroughs may
be able to treat patients who suffer from illnesses which endanger
CSMN cells. Corticospinal motor axons are responsible for sending
messages from the brain to the body in order to control the muscles.
If there is a breakdown in these cells, the brain will no longer be
able to control the muscles and paralysis and eventual death results.
Researchers in this study found that IGF-1 is
essential for the growth of CSM axons. If motor neurons are not
provided sufficient IGF-1, their axons will not grow sufficiently in
vitro. In addition to this, IGF-1 has been proven vitally important
in motor neuron maintenance in animal research as well. When IGF-1
production was suspended in laboratory mice, it was found that
Corticospinal motor axons did not grow as long or connect to adjacent
cells as efficiently.
IGF-1 Proven Vital to CSMN Axon Growth
Jeffrey Macklis is the director of the Center for
Nervous System Repair at Harvard Medical School. He is also the
primary author of the study. He says that the research conducted by
his team proves that IGF-1 has the ability to rapidly increase both
the rate at which corticospinal motor axons grow and the length at
which they grow. Axons are well known for their ability to extend
themselves long distances in comparison to the core cell. This study
is the first piece of evidence that directly shows that IGF-1
encourages the growth of corticospinal motor neurons.
Why is this Important?
Discovering this link is encouraging to Dr.
Macklis, because it adds to the body of knowledge regarding how CSMN
cells function and what stimuli help them develop. In addition to
that, this knowledge may lead to future breakthroughs involving
either IGF-1 or Human Growth Hormone in which we may eventually be
able to treat injuries of the spinal cord and neuron disorders such
as ALS more effectively. Today, the range of options are quite small,
but as the breadth of options increases with advances in medical
knowledge, it is almost inevitable that new techniques will arise
that will provide improved outcomes for these patients.
What makes Corticospinal Motor Neurons unique?
CSMN cells are unique among neuron cells within
the body. Their central bodies are located in the brain, but their
axons reach all the way from the brain to their target neuron in the
spinal cord. Some axons extend all the way to the tip of the spinal
cord, which in humans can be as long as three feet. Like most neurons
of the brain and spinal cord, these cells have an incredibly limited
capability to reproduce, and for this reason they are incredibly at
risk when severe spinal trauma or particular medical disorders
destroy their tissue.
Damage to these cells directly leads to paralysis
of the corresponding areas of the body which are controlled by the
particular group of Corticospinal Neurons. Although these axons are
incredibly long, they have been very difficult to study until quite
recently, because of the huge number of other types of neurons
occupying the same space within the cerebral cortex. There are
literally hundreds of kinds on neurons embedded within the tissue
contained by the spinal cord. As a result, we do not know a
significant amount about how CSMN cells grow and develop, although we
are keenly aware of their function and the effects of their atrophy.
Isolating CSMN Cells for Study
Because of the difficulty of studying living
Corticospinal Motor Neurons, Dr. Macklis and his post-doc research
fellow Dr. Hande Ozdinler had to come up with an innovative way to
remove CSMN cells from their natural environment and isolate them in
solitary populations in vitro. Through a mixture of biological
hypothesis and trial-and-error, Dr. Macklis discovered that IGF-1 was
one of the primary candidates which seemed to facilitate the growth
of CSMN cells.
By utilizing these isolated neurons, the duo was
able to prove in a laboratory environment that it was possible to
encourage the growth of Corticospinal Motor Neurons with the
application of IGF-1. They proved this in two ways. One way that they
achieved this growth was by directly applying IGF-1 to the purified
cultures. The second way was by applying IGF-1 to the purified
culture via microbeads coated in the hormone.
They found that CSMN axons grew by fifteen to
twenty times in length as a direct result of IGF-1 stimulation. In a
living system, this growth rate had only been observed during the
initial growth of the axons. When IGF-1 was removed from the system,
CSMN axons again only grew at the pace they did during the control
stage. This proves that IGF-1 is central to the complete development
of the Corticospinal Motor Axons.
A number of different experiments were conducted
after they had made the connection between IGF-1 and CSMN
development. In these experiments they tested the effect of IGF-1 on
another form of neuron and discovered that it had no appreciable
effect. They also tested other types of Human Growth Factor, applying
them to CSMN cells in order to see if any other hormones could
produce a similar effect. Only IGF-1 was able to rapidly increase the
rate at which CSMN cells developed.
IGF-1 only effects the CSMN Axon
Dr. Macklis and Dr. Ozdinler were also able to
show that IGF-1 did not play an active role in the survival
mechanisms of the core of the cell. It appears that IGF-1 only
encourages the rapid lengthening of CSMN axons rather than having any
influence on the central development of the cell. The duo performed
tests on living laboratory mice in which they blocked the pathway
which routed IGF-1 to the spinal cord. This alteration had no effect
on general cellular health but retarded the development of the CSMN
axons. This animal test proved that the in vitro evidence could be
applied to the biology of a living subject.
Understanding the Role of IGF-1 in
Corticospinal Motor Cells
Dr. Macklis says that fully revealing IGF-1s
role in the development of Corticospinal Motor Axons is vital to
fostering a more complete understanding about both how CSMN cells
function and how we can prevent or cure spinal disorders which
prevent CSMN Neurons from performing their necessary task of muscle
control.
Although it may still be a long ways off, studies
such as these represent the initial steps in creating treatments
which can alleviate degenerative disorders such as Lou Gehrigs
disease. In addition to this, if scientists can unlock the mechanism
by which the hormone IGF-1 develops CSMN axons, we may one day be
able to regenerate CSMN cells utilizing a mixture of IGF-1 therapy
and neuronal stem cells.
Dr. Macklis research was fostered by grants
from that Harvard Center for Neurodegeneration and Repair, the ALS
Association, and the National Institutes of Health.
This information was collected from information
released by Massachusetts General Hospital
The New and Exciting World of
Human Growth Hormone Research
We are just beginning to learn about the
fascinating ways in which hormones such as Human Growth Hormone and
IGF-1 maintain proper health and development. IGF-1 is an incredibly
versatile hormone which is derived from Human Growth Hormone. HGH is
secreted by the pituitary gland and converted into IGF-1 in the
liver. After converting into IGF-1, the hormone is distributed
throughout the body to perform various tasks.
We have long known that IGF-1 directly leads to
the breakdown of fatty tissue, enhancing weight loss and providing
energy and nutrients required for muscle development. There are many
other purposes of IGF-1 which we are just now discovering, and we
will likely be learning more about its fantastic physiological
benefits for decades to come. IGF-1 plays a central role in
anti-aging and long-term health maintenance as a result of its
interaction with fat and muscle tissue. Over time and as a result of
these studies, Hormone Replacement Therapy will become even more
popular as the litany of benefits continues to be unearthed.
The future of IGF-1 Treatments
What Dr. Macklis research shows is that IGF-1
also plays a significant role in regenerative medicine. Eventually,
IGF-1 will likely play a central role in genetic enhancement. This
study is perfect proof of that. There is a significant chance that
stem cells will be able to be repurposed as CSMN cells in the brain
and spinal cord.
If surgical implantation is possible, IGF-1 will
play a central role in restoring motor function to paralyzed
patients. Imagine a world where the paralyzed can walk again. Imagine
a world where diseases such as ALS are treatable, rather forces which
can only be stopped, not slowed. This is the future of Anti-Aging
Medicine, and HGH and IGF-1 will be key players in the race to 150.
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