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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 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.


HUMAN GROWTH HORMONE AFTER SURGERY


Written by Dr. Welsh, Published on 09 October 2018

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Human Growth Hormone May Improve Physical Therapy Outcomes in the Elderly

Human Growth Hormone Replacement Therapy has been shown to both increase Bone Mineral Density and Increase Lean Muscle in elderly patients. New evidence shows that HGH Hormone Replacement may offer another benefit: Increased healing capacity.

Dr. Robert Costa, professor of molecular genetics and biochemistry at the University of Illinois at Chicago, says that he and his staff have discovered that Human Growth Hormone has the ability to switch on a gene that is responsible for tissue to regenerate and heal more quickly. This function of HGH may help to explain one critical factor of the aging process: The older that we get, the harder that it is to recover from injury or tissue damage.

Aging is the Result of Ongoing Physical Breakdown

It is believed that one of the ways that the body physiologically ages is through a slow process of degradation, resulting from the body's reduced ability to heal efficiently. HGH Levels appear to have a distinct correlation with the speed at which our bodies can heal. Dr. Costa explains that the gene Foxm1b plays a critical role in the human body's ability to undergo repair. Foxm1b is turned on directly by Human Growth Hormone secretion, and as the body releases less HGH, Foxm1b loses its ability to efficiently restore tissue to a healthy state after damage or injury.

HGH Study in Hepatology

The study in which Dr. Costa participated in was released in the medical journal Hepatology. Although this study was conducted with animals, there is sufficient evidence to extrapolate the results of this animal research to human patients. Dr. Costa's study revolved around liver regeneration in both young and aging mice. The study compared two month old mice with twelve month old mice in regard to their capacity to recover from tissue damage in the liver.

The reason why the liver was chosen for this study is because of a particular unique trait: The liver can completely restore itself simply from a collection of mature liver cells. No other organ in the human body can completely rebuild itself with such a sparse set of resources.

The Importance of Foxm1b

Foxm1b is an important gene which plays a role in every aspect of the development of all mammalian cells. Foxm1b is active within all cells upon cell division, throughout the development of the cell, and until the cell finally surrenders to apoptosis at the end of its life cycle. Early in life, the Foxm1b gene is highly active, but as mammals age, the gene becomes less and less responsive.

Foxm1B Activation Heals Organs

In earlier research, scientists added the human form of Foxm1b into aging mice with livers which had been partially destroyed. Humans and mice have Foxm1b genes that are functionally identical, and serve nearly the exact same set of purposes within the body. Researchers found that adding the Foxm1b gene to damaged livers increased the speed at which the liver recovered from damage. The rate at which recovery occurred was similar to that of younger mice.

Upon further analysis, the study also showed exactly how the Foxm1b regulates the health and function of cells throughout the lifespan, encouraging them to undergo the process of cellular division more efficiently and more quickly.

The Correlation between HGH Exposure and Foxm1b Activation

In this study, the goal was to test the effect of HGH upon the rate at which cell division occurs in aging organisms. The previous study already made it clear that activated Foxm1b has the ability to increase regenerative capacity, and researchers hypothesized that Human Growth Hormone may have the capability to activate dormant Foxm1b cells, thus encouraging increased healing capacity later in the aging process.

What is the Role of HGH?

Human Growth Hormone is one of the most important hormones which regulate health and function throughout the lifespan. Earlier in life, HGH is recognized primarily for its ability to spur growth and adolescent development, but later in life, the role of Growth Hormone is primarily to maintain optimal health balance and regulate cellular metabolism.

As the aging process continues, the body is less able to self-regulate and repair itself, and this is believed to be at least partially the result of declining levels of Human Growth Hormone released by the Human Pituitary.

HGH Makes Cells Regenerate More Quickly

Dr. Costa says that there is evidence in the body of endocrinological research that HGH Hormone Replacement Therapy likely has the capacity to increase rates of cellular regeneration in aging patients. This is one of the primary reasons why changes in physical composition occur as a result of HGH Injections.

Increased cellular metabolism leads to increased lean muscle mass, increased bone mineral density, and stronger skin, because the body is repairing and replacing dying cells quickly and more effectively. Dr. Costa claims that the ultimate goal of his study is to discover how Human Growth Hormone functions at the molecular level, in order to uncover new medical purposes for HGH Replacement Therapy.

Foxm1b HGH Study Results

The results of the study were fairly dramatic. When the year old mice were administered HGH Injection, multiple tests showed that Foxm1b drastically increased in activity. In addition to this, other proteins and enzymes responsible for the process of cell division also became more active as well. At the organ level, the mice experienced physiological regeneration as a result of Human Growth Hormone Stimulation.

The damaged livers repaired more quickly as a result of treatment, healing at a rate which was comparable to that of healthy, youthful mice. The rate of efficiency of cellular division reached its peak after only 2 short days, and the liver was completely rehabilitated after only a single week. As opposed to aging mice in the experimental group, control mice which were not administered HGH did not experience total regeneration until at least one month after the damage occurred.

This means that, in the case of mice, HGH Hormone Replacement has the capacity to increase the rate at which liver rehabilitation takes place by over 400%. Of course, mice have metabolic processes which are much faster than our own (and thus, live shorter lifespans), but this study is proof of concept. Human Growth Hormone HRT can, and likely does, have the capacity to increase rate of healing in aging patients.

In mice that did not receive supplemental HGH, the Foxm1b gene stayed relatively dormant, limiting the rate at which cellular regeneration could take place. Without the rapid increase in cell regeneration spurred by Human Growth Hormone, the liver could only repair itself at a slow and limited pace.

Foxm1B Deactivation Blunts the Effect of HGH

Further testing examined the function of HGH upon Foxm1b activation from the opposite perspective. In a second group of mice, the rodents were genetically altered so that their livers contained Foxm1b genes that were totally inactivated. In this second experiment, mice acted physiologically according to Dr. Costa's hypothesis. When the Foxm1b gene is inactivated, it prevents HGH injections from having any appreciable effect upon cellular metabolism and physiological recovery.

Dr. Costa explains that the results of the research conducted by his academic team show that Foxm1b is a necessary ingredient which is required to encourage the regeneration of the liver after damage occurs. There is also strong reason to believe that Human Growth Hormone Replacement Therapy has the capability to increase the rate of physiological response in other tissues throughout the body as well.

Future Research will Improve our Knowledge of Foxm1b

Although Dr. Costa finds the results of his study promising, he still urges caution regarding the use of Human Growth Hormone Replacement Therapy. He explains that his study only explores the short term benefits of HGH Injection, but does not offer any information regarding the long term benefits or consequences of Human Growth Hormone Usage.

This study increases our knowledge of the mechanisms by which Human Growth Hormone can benefit the body at a molecular level, but Dr. Costa encourages further research and evaluation to take place before his data can be extrapolated fully to human patients.

Human Growth Hormone May Be Useful in Encouraging Physical Rehabilitation in Aging Patients

In the future, many are confident that HGH Injections can be utilized in elderly patients to increase physiological healing capacity and resiliency. There is hope that Human Growth Hormone can be used in urgent care situations in order to increase the speed of the healing process in order to more fully preserve the health of the elderly patient.

The Future of HGH Hormone Replacement Therapy

Perhaps in the future, a combination of therapies will become available in order to preserve health into old age. Since older patients tend to be more sensitive to Human Growth Hormone, it may be found that Sermorelin Acetate Injections can be a long-term solution to Age-Related HGH Deficiency which minimizes the risk of overdose and side-effects, while Growth Hormone Injections can be utilized in a rehabilitation setting to increase the effectiveness of the healing process while also stimulating cellular metabolism more directly.

Although Human Growth Hormone cannot be prescribed as an Anti-Aging Solution, in the future, as our knowledge of the benefits of the hormone become more complete, many restrictions on the use of the hormone will likely be lifted, and HGH can be utilized more fully as a tool of health optimization.

HGH May Be Beneficial in the Physical Rehabilitation Outcomes of Patients of All Ages

Although this study is primarily concerned with the concept of Human Growth Hormone as a tool to improve rehabilitation outcomes for older patients with low levels of innate Human Growth Hormone, there are also studies which show that Human Growth Hormone has the potential to benefit adults of all ages that are going through the process of physical rehabilitation and therapy.

In the case of cartilage repair, for example, it appears that Human Growth Hormone and IGF-1 have the capability to restore healthy cartilage tissue, minimizing pain and limited range of movement which is sometimes associated with cartilage surgery and damage. In addition to this, HGH Hormone Injections may also benefit patients that have recently undergone surgery, whether they are suffering from HGH Deficiency or not. Side-effects of Human Growth Hormone use are primarily associated with long-term use at abusive levels.

There are some that hypothesize that patients of all ages may be able to directly benefit from short term therapy using Human Growth Hormone in order to spur tissue regeneration and shorten downtime from injury or surgery.

Time will only tell, but it appears that in future years, HGH will find increased acceptance as a medical treatment, and medical professionals will gradually uncover more and greater benefits of HGH Hormone Replacement Therapy as a legitimate medical treatment.


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Study Shows New Method Of Growth Hormone Dosing Improves Height
ScienceDaily (Jun. 7, 2005) A randomized UCLA study found that a new dosing paradigm can improve height outcomes in the treatment of children who have short stature due to growth hormone deficiency and idiopathic short stature.
The groundbreaking study, presented at The Endocrine Society 2005 meeting in San Diego, Calif., challenges traditional approaches to growth hormone (GH) administration based upon weight.
The authors described a new dosing approach based on the serum levels of insulin-like growth factor-I (IGF-I), the growth hormone GH-dependent hormone that mediates the actions of growth hormone on the growth of children.
In the study, Dr. Pinchas Cohen, lead investigator and professor and chief of pediatric endocrinology at UCLA's Mattel Children's Hospital, along with his UCLA colleagues and collaborators from four institutions, randomized pre-pubertal children with growth hormone deficiency or short stature to one of three treatment arms: a conventional dose of growth hormone according to weight, or to one of two dosing arms where the dose was adjusted to achieve an IGF-I level that was either at the mean for age and gender, or at the upper limit of normal.
Study results showed that the change in height in children whose growth hormone dosage was increased to achieve a higher IGF-I level grew 50 percent better than children receiving fixed doses of growth hormone or whose IGF was maintained at the mean. Furthermore, the higher IGF-I arm resulted in a substantial improvement in the growth of both growth-hormone deficiency patients and patients with idiopathic short stature.
"We feel confident that IGF-based growth hormone dosing could become a novel paradigm in treating growth hormone deficiency, resulting in improved height increases for these children. The growth hormone dose targeted to achieve the higher IGF-I level produced especially meaningful increases in height compared to conventional weight-based methods of determining doses," Cohen said. "Also, the dramatic range of sensitivity to growth hormone in the study population substantiated the rationale for IGF-based dosing. This approach has important implications for both the safety and efficacy of GH."
###
This study was supported by an unrestricted grant from Novo Nordisk. Cohen is an investigator for Novo Nordisk and has received speaking honorariums from the company.
Source Science Daily
Adapted from materials provided by University Of California - Los Angeles Health Sciences.

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