Mar 26 2010
Neural Stem Cells and Plasticity
New research is expanding our knowledge of the nature of plasticity in the brain, creating the potential to treat a variety of neurological diseases and injury with transplanted stem cells.
At present the research is mostly in the proof of concept stage – doing animal studies to understand plasticity and the fate and function of neural stem cells. Plasticity is the ability of the brain to form new connections and pathways, even to change the pattern of its hardwiring. Plasticity is maximal when we are developing, and progressively declines with age. Although, even adults retain some plasticity and this likely results from the presence of neural stem cells (young cells capable of developing into new neurons) present even in the adult brain.
Further, all brain regions have a window of intense plasticity during which they are forming the majority of their connections. This development is closely tied to use, and if the brain is deprived of the appropriate sensory input or stimulation during this critical window of development, permanent deficits will develop. For examples, if children are not exposed to language by the age of 4 or so, their language window will close and they will never fully develop their language cortex. Or, if one eye is patched in young children, during the critical window in which binocular vision develops, they will never develop binocular vision.
University of California at San Francisco (UCSF) researchers, studying neural stem cell transplantation in mice, have been exploring the nature of these windows of high plasticity and have made some potentially useful discoveries. They isolated stem cells from the brain of embryonic mice and allowed them to age for various numbers of days. Meanwhile they patched one eye of other mice during their critical window of visual development, which results (due to the high degree of plasticity) in the visual cortex forming more connections to the open eye and fewer connections to the patched eye (called ocular dominance plasticity). This plasticity does not happen in more mature mice, after the critical window closes.
They then transplanted neural stem cells of various ages into mature mice, who were too old to display ocular dominance plasticity, to see if this would create a new period of such plasticity. They found that stem cells that were 33-39 days old (but not younger or older) resulted in ocular dominance plasticity. They also demonstrated that the stem cells distributed themselves throughout the cortex, matured, and formed connections.
What this likely means is that the period of increased plasticity is determined by the age of the neurons themselves, specifically inhibitory neurons that release the neurotransmitter GABA. If there are 33-39 day-old GABA producing neurons present, there is plasticity.
There are several important proofs of concept here: neural stem cells can be transplanted and will survive and make meaningful connections; the window of maximal plasticity is largely determined by factors intrinsic to the neurons themselves (rather than some other mechanisms of signaling); and the window of plasticity can be recreated by transplanting stem cells of the appropriate age.
This all bodes well for the potential of neural stem cells to treat a variety of conditions – traumatic brain injury, Parkinson’s disease, stroke, cortical blindness, and maybe even Alzheimer’s disease. Any traumatic, developmental, or degenerative neurological condition in which the problem is dying or damaged neurons could potentially benefit.
Of course, we need to extend this research to humans. The method of obtaining neural stem cells in this research would not be possible in humans, and so other methods would need to be developed. But there is already extensive and growing research showing the potential to derive stem cells from adult tissue.
Extrapolating technology is always tricky, but with the various proofs of concept already established by research we can easily imagine a future (once all the pesky technical details are worked out) in which a patient with one of the diseases I listed above or similar condition will have some of their fat cells (or some other cells) removed and then turned into stem cells. These stem cells will then be coaxed into forming neural stem cells and allowed to mature to the optimal age, and then transplanted back into the brain of the patient (either in a specific damaged location or more diffusely, as appropriate). Perhaps this treatment would have to be given multiple times. The stem cells will make connections, and due to plasticity will form the needed pathways, restoring function.
How long these new neurons will survive, and if they will fall prey to the original disease are important questions that later research will have to answer. Ideally, this type of treatment will result in young and vigorous brain cells that will last another lifetime.
This raises some further interesting, if speculative, questions. Would such treatments be useful for the brain atrophy and decline of function that most people (but interestingly not all) experience with normal aging? Will this technology make the “senior moment” a thing of the past?
Further, will such treatments be useful in making healthy young individuals smarter? Can an injection of neural stem cells before engaging in study or training enhance the benefits? Want to learn to speak a new language without an accent – no worries, just get an autologous transplant of neural stem cells in your language area and you are 3 years old again, ready to soak up a new language complete with all the phonemes.
Another interesting question is this – what if someone with severe Alzheimer’s disease, in which the brain steadily atrophies until more than half of the brain cells are lost (and this would continue if the patient did not eventually die first), were treated with neural stem cells. The new cells replace the old, making connections, and restoring and maintaining cognitive function. After years of such treatment, most of the brain’s original neurons will have died and been replaced by new neurons. Will this still be the same person?
Of course, the simple answer is yes. But I am interested in neurological function. It’s possible that if the process were slow enough there could conceivably be no cognitive changes – all the memories, personality, and talents will still be present. But that is the question – could this process slowly change the person neurologically, so that after 10 years and most of the brain being replaced the patient will actually be a different person in some meaningful respects. Will they have still lost some of their memories, will their personality and abilities change? Will they be almost like a newborn person (although with a very slow birth process)?
I don’t think we will know unless and until we achieve this kind of treatment.
In any case, the research into neural stem cells is consistently moving in a very encouraging direction. So far, so good. It certainly would be a good thing if this technology ushers in a new age of restoring damaged brains. Right now treatments are mostly limited to treating symptoms, compensating for damage, or maybe slowing down the progression of degenerative diseases. In some cases we can support the limited self-repair potential of brains (relevant to injuries but not degenerative disorders). But there is no way to directly repair damaged brains. That would be a welcome addition to our repertoire.
16 Responses to “Neural Stem Cells and Plasticity”
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Wow, very fascinating. As someone who has witnessed family members suffer from Parkinson’s disease this is exciting news, even though only preliminary.
I can see how this could help restore localized areas of the brain that have been damaged, however, I am unsure how this process would work when attempting to restore a function that requires connections across multiple areas. It seems a tall order to implant cells in all the right places and the connections to be established just right.
If only Philip K Dick were still around, I see some good sci-fi opportunities from the new brain/new person scenario.
The proliferation of neural stem cells that migrate to the dentate gyrus/hippocampus from the lateral ventricles decreases as we age. One of the things I’ve always wished someone would try is to stimulate the multipotent cells there to start increasing their numbers, closer to that of a previous state. This may be a new way to accomplish the same goal. Very elegant in design too!
question: When a hemispherectomies is performed, does the patient lose memories prior to the surgery?
If I got Philip Dick’s stem cells, would I start writing creepy science fiction stories?
This is a very interesting post discussing an exciting area of research, thanks!
Being a linguist (well, linguist-in-training I guess, I’m a grad student), I’d like to comment on the points about language acquisition. It is a common hypothesis that there is a critical, or sensitive, period for first language acquisition, with the upper limit of that period ranging from 4 to young adolescence. However, there is no conclusive evidence for this hypothesis. Why? Because it’s highly unethical to deprive babies and children of exposure to language just to see if they can go on to later acquire language! There have been some cases where this has actually happened though, the two most famous cases being the ‘Wild Child’ found in France in the late 18th century, and Genie, the young girl found by authorities in California in the ’70s. In both of these cases, the children were presumed not to have been exposed to any language prior to their discovery, and subsequent attempts to teach them language were not very successful. This fact goes some way to supporting the critical period hypothesis, but there are confounds in both cases. In the case of the ‘Wild Child’ he was described as having a large scar on his head, possibly indicative of head trauma. So it’s possible that he suffered from some form of brain damage which was responsible for his inability to acquire language. In the case of Genie, this young girl was subjected to both physical and psychological abuse prior to being found, which undoubtedly had profound psychological effects on her, which could have in turn affected her ability to acquire language. Still, the critical period hypothesis gets some support from the fact that second language acquisition, especially as an adult, is a very different kettle of fish to first language acquisition.
I also agree with the point made by CrookedTimber that his process could be very difficult when multiple brain areas are involved, which is definitely the case for language. But I hope this new research in neural plasticity will eventually help expand our knowledge concerning the fascinating (yes, I know I’m biased!) topic of language.
http://www.medicalnewstoday.com/articles/183708.php
Arnold Kriegstein at UCSF just came out with another paper today quickly firming up your speculations about therapeutic use of stem cells for treatment in Parkinsons etc… (see above link). He showed that transmission of embryonic neural progenitors into parkinsonian rats showed extensive migration into the striatum and differentiation into GABAergic internuerons… Its is amazing, they know just where to go and just what to do!
I think you’re right about the potential revolution in medicine around iPSc’s (induced pluripotent stem cells) from fats, neurons and other tissue but I suspect you’ll see this sooner than you think. Even if we don’t, a paper just came out showing neuron differentiation and regrowth in the cortex after ischemic stroke, isolating the genetic pathway for this event could induce the same end at cheaper means with native hippocampal pluripotent populations (less mess).
typos?
“a patient with one of the diseases…will have some of their fat cells…removed and then turned into stem cells. These stem cells will then be coaxed into forming neural stem cells and allowed to mature to the optimal age, and then transplanted BACK into the brain of the patient.”
The word “back” should be removed.
The cells did not come from the brain, but from fat cells.
“just get an autologous transplant of neural stem cells IN your language area and you are 3 years old again”
“in” should be “into”
CrookedTimber,
You just had a senior moment!
“I can see how this could help restore localized areas of the brain that have been damaged, however, I am unsure how this process would work when attempting to restore a function that requires connections across multiple areas. It seems a tall order to implant cells in all the right places and the connections to be established just right.”
From the article:
“They also demonstrated that the stem cells distributed themselves throughout the cortex, matured, and formed connections.”
I can’t see the value in adding neural stem cells to an aged brain,i.e., the elderly patient. The brain ages and becomes smaller. It would be like adding more make-up to Bozo the clown.
In response to Watcher’s comment: NSCs in the subventricular zone migrate rostrally to the olfactory bulb, not to the hippocampus. The dentate gyrus is the other major site of adult neurogenesis, with its own resident neural progenitors.
Steven, you referred to methods for making NSCs from other cell types (e.g., fat cells). Are you aware of iPS cells? I would assume you are. They’ve been all the rage the last few years in the stem cell community. They are genetically reprogrammed fibroblasts that are just the technology to which you refer. With the insertion of a handful of genes, fibroblasts (easily obtainable via biopsy) are induced into a state of pluripotency and offer potential avenues for patient-specific therapies. There would be no immune suppression necessary for transplants. Of course, like all new technologies, it’s important to wait for the hype to die down so that the science can be done to see what these cells are really capable of.
HHC:
The brain gets smaller with age partly because it loses neurons and possibly because the remaining ones are smaller. Somatic cells that don’t undergo mitosis accumulate mutations and metabolic gunk like altered products of fat and protein that the breakdown enzymes can’t deal with. So adding new neurons could lead to regaining the lost volume.
I’m not sure anyone has shown that the new cells will differentiate to replace all the types of neurons that are lost and replicate the little local networks of connections. It may require conditions and growth factors that are only present during normal development. If all the cell types are replaced this might lead to complete functional restoration of most of the brain. Memory would be interesting. Possibly there’s some kind of rehearsal or recall process that would transfer memories to the new neurons.
But practical stuff like that is boring, compared with the fantasy of getting stem cells from, say, Brad Pitt so you could get all the grrlz. And if only L. Ron weren’t deceased, you could become a Clear in a few weeks without all the auditing and E-meters and stuff. Or failing that, acquire the talent to start a lucrative cult.
Oh yeah? Well, using stem cells to repair half-decayed brains seems to be a very bad idea …
Perhaps neural stem cells could even be used to remove undesirable mental traits that have become hardwired and are close to impossible to elliminate in adults, such as a tendency to violence and antisocial behavior in delinquents that will spend most of their life in jail with one sentence after another, or the attraction to children in pedophiles. Of course, the idea comes to mind about whether it would be ethical or a misuse to change other hardwired traits that some consider undesirable and others don’t, such as homosexuality (which even today some pretend to “cure” but they actually don’t). And, of course, the technology could give “brainwashing” a whole new meaning. That does sound indeed like something out of a Philip K. Dick story.
The cells could also be used to make enhancements to the brain that make the electronic add-ons of cyberpunk SF look primitive by comparison. Imagine adding to your brain not only the capacity to learn new languages, but processing modules that make phenomena explained by quantum mechanics, relativity theory or string theories be understood intuitively the way we already do with Newtonian mechanics. Can you imagine the possibilities for new science theories and understanding reality?
As an avid fan of all things Novella, I’ve been expecting to wait a while for stem cell research to benefit humans. What then to make of this? http://brodiegolfclassic.org/
The claim made here is that NFL quarterback John Brodie suffered a stroke in 2000, got “stem cell treatment” and now he is back to talking and walking. Science or fiction?
Fiction.
People do recover partially or completely from stroke.
Medications can help but, as yet, there is no evidence to support the use of stem cells in any condition.
There are plenty of charlatans, though, willing to relieve people of their hard earned cash. There is a certain Dr. William Rader, for example, living in a mansion overlooking the pacific ocean bought with the blood of innocent people…
By chance, last night the ABC’s “Foreign Correspondent” did a sceptical piece on stem cell treatment available in places like Russia, Tijuana, and the Dominican Republic. They followed a family with a child with a rare disorder causing blindness. Their community raised the $20,000 to take her over to the last mentioned destination. On their return they were convinced their daughter could now see and the media proclaimed a miracle had occurred. The scientists tested her and found no difference in her vision. The parents remain convinced she can see.
http://www.abc.net.au/foreign/
Dr Joanne Kurtzberg at Duke has had some promising results with autologous, cord blood-derived, stem cell transplants for children.