Neural Plasticity and the Legions of Stem Cells in the Brain

Neural plasticity - the ability of the brain to generate new neurons and make good use of them in its circuitry - is a topic of growing interest in the research community. That adult brains continue to create and assimilate new neurons was a comparatively recent discovery, first made in the 1960s, but lacking conclusive proof until the 1990s. Unfortunately, the pace at which this happens declines with age. Neurogenesis, the creation of neurons, requires an active neural stem cell population, and as appears to be the case for all stem cell populations, those in the brain decline in their activities with age. At the high level this is generally thought to be an evolutionary adaptation related to cancer, a part of the evolved balance between maintaining tissues and suppressing those maintenance activities when cellular damage (which grows with age) raises the odds of spawning a cancer.

It is thought that there are benefits to be gained by boosting the pace at which new neurons are created in old individuals. Aims include restoring the general loss of cognitive function that occurs with aging, developing new types of treatment for the named neurodegenerative diseases, and so forth. This ties into much of the present ongoing work on stem cells and aging: why do they stop performing their tasks; do they decline in number or just stop working; what exactly are the biochemical cues involved? The answers are emerging piece by piece, probably broadly similar but different in detail for every different stem cell population. The best outcome we can hope for is that all stem cell declines are a reaction to growing levels of damage and disarray in cells and cellular machinery - and thus the development of therapies to repair that damage will lead stem cell populations to revert to youthful behaviors without the need for further intervention.

Here are a few recent articles from the research world on the topic of neural plasticity, starting with one that pulls the ever-important processes of autophagy into the picture:

Spring Cleaning in Your Brain's Stem Cells?

Deep inside your brain, a legion of stem cells lies ready to turn into new brain and nerve cells whenever and wherever you need them most. While they wait, they keep themselves in a state of perpetual readiness -- poised to become any type of nerve cell you might need as your cells age or get damaged. [New research reveals] a key way they do this: through a type of internal "spring cleaning" that both clears out garbage within the cells, and keeps them in their stem-cell state.

It is the first time that this cellular self-cleaning process, called autophagy, has been shown to be important to neural stem cells. The findings may help explain why aging brains and nervous systems are more prone to disease or permanent damage, as a slowing rate of self-cleaning autophagy hampers the body's ability to deploy stem cells to replace damaged or diseased cells. If the findings translate from mice to humans, the research could open up new avenues to prevention or treatment of neurological conditions.

Producing New Neurons Under All Circumstances

Improving neuron production in elderly persons presenting with a decline in cognition is a major challenge facing an aging society and the emergence of neurodegenerative conditions such as Alzheimer's disease. [Researchers] recently showed that the pharmacological blocking of the TGFβ molecule improves the production of new neurons in the mouse model. These results incentivise the development of targeted therapies enabling improved neuron production to alleviate cognitive decline in the elderly and reduce the cerebral lesions caused by radiotherapy.

Neither heavy doses of radiation nor aging are responsible for the complete disappearance of the neural stem cells capable of producing neurons (and thus the origin of neurogenesis). Those that survive remain localised in a certain small area of the brain (the sub-ventricular zone (SVZ)). They nevertheless appear not to be capable of working correctly. Additional experiments have made it possible to establish that in both situations, irradiation and aging, high levels of the cytokine TGFβ cause the stem cells to become dormant, increasing their susceptibility to apoptosis [and] reducing the number of new neurons. [Researchers then] demonstrated that pharmacological blocking of TGFβ restores the production of new neurons in irradiated or aging mice.

Assessing brain plasticity across the lifespan with transcranial magnetic stimulation

Sustaining brain and cognitive function across the lifespan must be one of the main biomedical goals of the twenty-first century. We need to aim to prevent neuropsychiatric diseases and, thus, to identify and remediate brain and cognitive dysfunction before clinical symptoms manifest and disability develops. [Therefore], assessing the mechanisms of brain plasticity across the lifespan is critical to gain insight into an individual's brain health.

Indexing brain plasticity in humans is possible with transcranial magnetic stimulation (TMS), which, in combination with neuroimaging, provides a powerful tool for exploring local cortical and brain network plasticity. [Ultimately], TMS measures of plasticity can become the foundation for a brain health index (BHI) to enable objective correlates of an individual's brain health over time, assessment across diseases and disorders, and reliable evaluation of indicators of efficacy of future preventive and therapeutic interventions.

Comments

"Deep inside your brain, a legion of stem cells lies ready to turn into new brain and nerve cells whenever and wherever you need them most."

When will popular science articles stop saying things like this that are manifestly untrue? Whenever an exciting discovery like adult neurogenesis happens, they start proclaiming an inaccurate cartoon version of it and confusing their lay readers. Now most of the "educated public" thinks that neurogenesis goes on all throughout the brain "whenever and wherever" needed, and they conflate neuroplasticity (of which there are many types) with neurogensis (a relatively minor contributor to neuroplasticity in adults). Sometimes I wonder if the the popular scientific press harms scientific literacy more than it helps.

Maybe it is possible to steer the migration and differentiation of neural stem cells so that they can be directed to restore function in many diverse brain areas, but if so that will be a feat of engineering and one for which the resources might be more forthcoming if the media weren't bent on luring people into complacency with falsehoods.

Posted by: José at April 10th, 2013 11:29 PM

@José: Where there are issues, I'm given to think that research center publicity groups bear at least as much fault as the press that make use of them. Most of these popular science research reports are essentially just reprints of materials provided by the universities, medical centers, etc, etc.

Posted by: Reason at April 11th, 2013 8:56 AM

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