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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 11 of 11. This is the beginning of the thread.
Posted by Phillipa on September 27, 2013, at 18:28:10
What Not to Prescribe: APA List Aims to Make Patients Safer
Medscape Medical News > PsychiatryBone Protein May Influence Age-Related Cognitive Decline
Megan Brooks
Sep 26, 2013
Osteocalcin, a bone-specific protein, may influence brain development and cognitive function, a finding that could lead to new approaches to the prevention and treatment of age-related cognitive decline, including Alzheimer's disease, a new animal study suggests.In what one expert described as "potentially groundbreaking research," a series of studies by researchers at Columbia University Medical Center in New York City showed that osteocalcin crosses the blood-brain barrier and influences neurotransmitter synthesis and neurogenesis, as well as spatial learning and memory.
"As we age, bone mass decreases, and the production of osteocalcin probably does too. It is not inconceivable that treatments that boost osteocalcin levels or stimulate osteocalcin receptors could help counter the cognitive effects of aging and aging-related diseases such as Alzheimer's," team leader Gerard Karsenty, MD, PhD, chair of the Department of Genetics and Development, Columbia University Medical Center, said in a statement.
The research was published online September 26 in the journal Cell.
Therapeutic Potential?
The "powerful regulation" of bone mass exerted by the brain points to the existence of bone-derived signals modulating this regulation or other functions of the brain, the investigators note.
They conducted a series of studies in mice to flush out the role of osteocalcin in the brain. They showed that osteocalcin crosses the blood-brain barrier, binds to neurons in the brainstem, midbrain, and hippocampus, which is responsible for learning and memory, promotes neurogenesis, and increases the synthesis of several neurotransmitters, including serotonin, dopamine, and catecholamine.
They also observed that mice that were genetically engineered to lack osteocalcin have abnormally small hippocampi and exhibit increased anxiety and depressionlike behavior, as well as impaired learning and memory, relative to wild-type mice.
When osteocalcin-null mice are infused with osetocalcin, their anxiety and depression decreases, but there is no effect on learning and memory or hippocampal size, the researchers note.
The investigators also found evidence that osteocalcin acts during development. It crosses the placenta from mother to fetus, and this maternal pool of osteocalcin is necessary for formation of the hippocampus and the establishment of memory. They observed that injections of osteocalcin in osteocalcin-null mothers during pregnancy prevent the development of behavioral abnormalities in their offspring.
Dr. Gerard Karsenty
The "therapeutic potential" of this research is 2-fold, said Dr. Karsenty "One could envision that osteocalcin should prevent the decrease in cognitive functions during aging; the second one is that in countries where women are undernourished (a third of the world), osteocalcin injections prevent appearance of metabolic and psychiatric disorders in their offspring," he explained.
The next research step, Dr. Karsenty said, is to "extend the work to other animal models, to better define the molecular signaling of osteocalcin in the brain."
"Novel, Potentially Groundbreaking"
Commenting on the findings for Medscape Medical News, Clifford J. Rosen, MD, director of the Center for Clinical and Translational Research, Maine Medical Center Research Institute in Scarborough, who was not involved in the study, said the research is "novel and potentially groundbreaking, as it opens up an entirely new aspect of skeletal control over whole-body homeostasis."
He added that there are "several major questions and implications" that arise from this research.
"Since there is age-related bone loss in virtually all individuals, it is conceivable that this process directly influences cognitive function through release of undercarboxylated osteocalcin," he noted.
"It is well established that falls and fractures are commonly associated in cognitively impaired elders, but this would be the first to suggest that the 2 processes are tightly linked in a causal manner."
These studies also point to osteocalcin as a "potentially important modulator of mammalian aging, since it has been shown to regulate glucose homeostasis, male fertility, and cognitive function," Dr. Rosen said.
He added that it is logical that osteocalcin, a bone-specific protein, could have endocrine activities, because its circulating levels are relatively high.
"Moreover, nerves and their dendritic and axonic processes resemble the structure of the osteocyte, the most common cell type in the skeleton. Many investigators have started to find common developmental switches in both neurons and osteoblasts/osteocytes, suggesting there is a potentially shared series of regulatory loops," said Dr. Rosen.
"Notwithstanding the enormous opportunities this work may provide in terms of testable hypotheses, studies in humans will have to be foremost to validate that the regulatory actions of osteocalcin in mice have relevance in the development and aging of humans," he added.
Another POV
Peter R. Schofield, PhD, executive director and chief executive officer of Neuroscience Research Australia, who was not involved in the study, described the research as a "nice fundamental study showing the complexity of signaling molecules and brain development."
"I don't think you have to conclude that the skeleton is important for brain development, as there are many molecules that have multiple effects in the body; it's just that while the brain effect was not known, the skeletal one was," Dr. Schofield said.
The study was supported by grants from the National Institute on Aging, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, Sanofi Aventis, the Human Frontier Scientific Program, and by a National Institute of Health Directors Pioneer Award and an Ellison Medical Foundation Senior Scholar Award. Columbia University has filed for patents relating to osteocalcin and its use to treat a variety of conditions. The authors, Dr. Rosen, and Dr. Schofield report no relevant financial relationships.
Posted by Tomatheus on September 27, 2013, at 23:53:15
In reply to Bone Protein May Influence Cognitive Decline, posted by Phillipa on September 27, 2013, at 18:28:10
It seems that a metabolite of vitamin D3 (1,25-(OH)2D3) can increase the synthesis of osteocalcin:
http://www.ncbi.nlm.nih.gov/pubmed/3873510
http://www.jbc.org/content/260/15/8706.full.pdf
This evidence that osteocalcin may influence brain health seems like it could very well be yet one more reason to supplement with vitamin D and/or increase sun exposure (sensibly, of course), especially for those whose blood levels of the vitamin are deficient or insufficient. It would at least make sense that if one is low in vitamin D that one is also probably going to be low in both 1,25-(OH)2D3 and osteocalcin. It also makes sense that increasing one's vitamin D intake should likely reverse these problems.
T.
Posted by Phillipa on September 28, 2013, at 9:39:25
In reply to Re: Bone Protein May Influence Cognitive Decline, posted by Tomatheus on September 27, 2013, at 23:53:15
How did you learn all of this. Until this article I'd never heard of this bone protein. Just knew osteoclasts and osteoblasts. Since I have osteoporosis of spine, hips and it seems the thoracic spine is the worst any idea how to slow it down or is there a way to "fix" it? Seriously as been doing PT and seeing spinal neurosurgeon for almost two years now. Started with all the pain from osteoarthritis all over my spine? Phillipa
Posted by Tomatheus on September 28, 2013, at 13:08:30
In reply to Re: Bone Protein May Influence Cognitive Decline » Tomatheus, posted by Phillipa on September 28, 2013, at 9:39:25
Given what the article said about osteocalcin being a bone-specific protein that may influence brain health, I was curious as to how this protein might be related to vitamin D, so I just did some Googling and found the articles that I linked to in my previous post.
As far as osteoporosis is concerned, here's a snippet of what Michael F. Holick, Ph.D., M.D., had to say about it as it relates to vitamin D: "Vitamin D deficiency can cause osteoporosis, and it can make it worse. Even when people are consuming enough calcium, numerous studies have shown that they still will not build and maintain bone mass if they are deficient in vitamin D. And even more studies have shown that people who suffer from osteoporosis often have vitamin D deficiency. (Holick, 2010, pp. 59-60)."
Have you had your vitamin D blood level tested any time recently? If you haven't, doing so might be a good idea, because of the role that vitamin D might play both in bone health and brain health.
T.
==
REFERENCE
Holick, M.F. (2010). The Vitamin D Solution. New York: Hudson Street Press.
Posted by Phillipa on September 28, 2013, at 20:13:45
In reply to Re: Bone Protein May Influence Cognitive Decline » Phillipa, posted by Tomatheus on September 28, 2013, at 13:08:30
Last time Vita D levels checks over 55 which was supposed to be good ? Phillipa
Posted by Tomatheus on September 28, 2013, at 20:56:20
In reply to Re: Bone Protein May Influence Cognitive Decline » Tomatheus, posted by Phillipa on September 28, 2013, at 20:13:45
> Last time Vita D levels checks over 55 which was supposed to be good ? Phillipa
Yes, both Dr. Michael F. Holick and Dr. Soram Khalsa (author of "The Vitamin D Revolution") would consider a vitamin D level of 55 ng/mL to be in the optimal or ideal range.
Given your background, you probably have a much better understanding of osteoporosis than I do, so I'm not sure that there's much else that I could say that might be of some help. I've been doing a lot of reading on vitamin D lately, and so I've been trying to get the word out about the role that vitamin D may play in various health conditions, but with a vitamin D level of 55, it would seem that you're getting enough of the vitamin (or hormone, to be more accurate).
I'm sorry that I couldn't be of more help.
T.
Posted by Tomatheus on September 28, 2013, at 21:00:44
In reply to Re: Bone Protein May Influence Cognitive Decline » Phillipa, posted by Tomatheus on September 28, 2013, at 13:08:30
> REFERENCE
>
> Holick, M.F. (2010). The Vitamin D Solution. New York: Hudson Street Press.
>I'm correcting the above reference so the title is hyperlinked. Here's the corrected version:
REFERENCE
Holick, M.F. (2010). "The Vitamin D Solution". New York: Hudson Street Press.
T.
Posted by Phillipa on September 28, 2013, at 21:12:22
In reply to Re: Bone Protein May Influence Cognitive Decline » Phillipa, posted by Tomatheus on September 28, 2013, at 20:56:20
From various research I've also done and from what the PT guy and neurosurgeon say "Thank my genetics, and then I over used my body with all the running, and teaching Aerobic Dance, and all the bedside nursing. Bending, lifting dead weight of who knows how many pounds at times. But evidently there are now clinical trials of harvesting ones own stem cells and injecting into the most affected part of spinal column. Also having breasts lifted or reduced was told would hold off further degeneration of thoracic spine. Trying to make one of these work. If push comes to shovel and can't get medicaire to help I guess somehow get the surgery done and be broke. Rather be broke money wise than broke body wise. Phillipa
Posted by Tomatheus on September 28, 2013, at 21:51:55
In reply to Re: Bone Protein May Influence Cognitive Decline » Tomatheus, posted by Phillipa on September 28, 2013, at 21:12:22
The stem-cell treatment sounds interesting. I wish you much luck in finding a treatment option that will work out well for you.
T.
Posted by Phillipa on September 29, 2013, at 20:00:52
In reply to Re: Bone Protein May Influence Cognitive Decline » Phillipa, posted by Tomatheus on September 28, 2013, at 21:51:55
Google Carolina neurosurgery & Spine Charlotte Nc a video on the newest trials. The stem cell one is done and now another taking place. The doc conducting the trials is the video speaker. Phillipa
Posted by Tomatheus on September 29, 2013, at 22:27:32
In reply to Re: Bone Protein May Influence Cognitive Decline » Tomatheus, posted by Phillipa on September 29, 2013, at 20:00:52
Thanks, Phillipa. I'll take a look at it.
T.
This is the end of the thread.
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