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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HGH / IGF-1: Growth Factor Stimulates Rapid Extension Of Key Motor Neurons In Brain