Scientists sniff out unexpected role for stem cells in the brain

Scientists sniff out unexpected role for stem cells in the brain
Making “scents” of new cells in the brain’s odor-processing area Adult-born cells travel through the thin rostral migratory stream before settling into the olfactory bulb, the large structure in the upper right of the image. Credit: Belluscio Lab, NINDS.

For decades, scientists thought that neurons in the brain were born only during the early development period and could not be replenished. More recently, however, they discovered cells with the ability to divide and turn into new neurons in specific brain regions. The function of these neuroprogenitor cells remains an intense area of research. Scientists at the National Institutes of Health (NIH) report that newly formed brain cells in the mouse olfactory system—the area that processes smells—play a critical role in maintaining proper connections. The results were published in the October 8 issue of the Journal of Neuroscience.

"This is a surprising new role for brain stem cells and changes the way we view them," said Leonardo Belluscio, Ph.D., a scientist at NIH's National Institute of Neurological Disorders and Stroke (NINDS) and lead author of the study.

The is located in the front of the brain and receives information directly from the nose about odors in the environment. Neurons in the olfactory bulb sort that information and relay the signals to the rest of the brain, at which point we become aware of the smells we are experiencing. Olfactory loss is often an early symptom in a variety of neurological disorders, including Alzheimer's and Parkinson's diseases.

In a process known as neurogenesis, adult-born neuroprogenitor cells are generated in the subventricular zone deep in the brain and migrate to the olfactory bulb where they assume their final positions. Once in place, they form connections with existing cells and are incorporated into the circuitry.

Dr. Belluscio, who studies the olfactory system, teamed up with Heather Cameron, Ph.D., a neurogenesis researcher at the NIH's National Institute of Mental Health, to better understand how the continuous addition of new influences the circuit organization of the olfactory bulb. Using two types of specially engineered mice, they were able to specifically target and eliminate the stem cells that give rise to these new neurons in adults, while leaving other olfactory bulb cells intact. This level of specificity had not been achieved previously.

In the first set of mouse experiments, Dr. Belluscio's team first disrupted the organization of olfactory bulb circuits by temporarily plugging a nostril in the animals, to block olfactory sensory information from entering the brain. His lab previously showed that this form of causes certain projections within the olfactory bulb to dramatically spread out and lose the precise pattern of connections that show under normal conditions. These studies also showed that this widespread disrupted circuitry could re-organize itself and restore its original precision once the sensory deprivation was reversed.

However, in the current study, Dr. Belluscio's lab reveals that once the nose is unblocked, if new neurons are prevented from forming and entering the olfactory bulb, the circuits remain in disarray. "We found that without the introduction of the new neurons, the system could not recover from its disrupted state," said Dr. Belluscio.

To further explore this idea, his team also eliminated the formation of adult-born neurons in mice that did not experience sensory deprivation. They found that the olfactory bulb organization began to break down, resembling the pattern seen in animals blocked from receiving sensory information from the nose. And they observed a relationship between the extent of stem cell loss and amount of circuitry disruption, indicating that a greater loss of led to a larger degree of disorganization in the olfactory bulb.

According to Dr. Belluscio, it is generally assumed that the circuits of the adult brain are quite stable and that introducing new neurons alters the existing circuitry, causing it to re-organize. "However, in this case, the circuitry appears to be inherently unstable requiring a constant supply of new neurons not only to recover its organization following disruption but also to maintain or stabilize its mature structure. It's actually quite amazing that despite the continuous replacement of cells within this olfactory bulb circuit, under normal circumstances its organization does not change," he said.

Dr. Belluscio and his colleagues speculate that new neurons in the olfactory bulb may be important to maintain or accommodate the activity-dependent changes in the system, which could help animals adapt to a constantly varying environment.

"It's very exciting to find that new neurons affect the precise connections between neurons in the olfactory bulb. Because new neurons throughout the brain share many features, it seems likely that neurogenesis in other regions, such as the hippocampus, which is involved in memory, also produce similar changes in connectivity," said Dr. Cameron.

The underlying basis of the connection between neurological disease and changes in the olfactory system is also unknown but may come from a better understanding of how the sense of smell works. "This is an exciting area of science," said Dr. Belluscio, "I believe the olfactory system is very sensitive to changes in neural activity and given its connection to other brain regions, it could lend insight into the relationship between olfactory loss and many disorders."

Explore further

Map of brain connections provides insight into olfactory system

More information: "Adult Neurogenesis Is Necessary to Refine and Maintain Circuit Specificity." Journal of Neuroscience, 8 October 2014, 34(41): 13801-13810; DOI: 10.1523/JNEUROSCI.2463-14.2014
Journal information: Journal of Neuroscience

Citation: Scientists sniff out unexpected role for stem cells in the brain (2014, October 13) retrieved 22 August 2019 from
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Oct 13, 2014
Made possible by the founding mother of neurogenesis in the year 2000:

The Schering Stiftung awards the 2014 Ernst Schering Prize to Prof. Dr. Magdalena Götz, director of the Institute of Stem Cell Research at the Helmholtz Zentrum München, for her groundbreaking research on the molecular underpinnings of brain development.

For decades scientists thought...

...and now her research is accepted.

Oct 13, 2014
From Fertilization to Adult Sexual Behavior http://www.hawaii...ion.html

"Molecular epigenetics. It is now understood that certain genes undergo a process called "genomic or parental imprinting." Early in embryonic development attached methyl groups become removed from most genes. Several days later, methyl groups are reattached in appropriate sites. Fascinatingly, some such genes reestablish methylation patterns... "

The link from ecological variation to nutrient-dependent RNA-directed DNA methylation via pheromone-controlled RNA-mediated events and cell type differentiation was clear in 1996.

Nothing about the conserved molecular mechanisms in species from microbes to man has changed. RNA-mediated amino acid substitutions differentiate all cell types of all individuals of all species. For examples, see:

Nutrient-dependent/pheromone-controlled adaptive evolution: a model. http://www.ncbi.n...24693353

Oct 14, 2014
Your commentary is not saved to your account.
Ratings as well.
Who or what is NOM?

Oct 14, 2014
@NOM Mutual feedback (commentary) is valuable.
One way commentary makes no sense.

Oct 14, 2014

1) "Unless you've been living under a rock the past two years, you've heard of CRISPR/Cas9, an RNA-guided nuclease that's redefining synthetic biology and genome engineering."

2) "The authors propose several additional applications as well, including... altering pre-mRNA splicing, and transcript tracking in live cells."

Are you an evolutionary theorist or evolutionary theist who has continued to ignore everything known about RNA-mediated events that link nutrient-uptake to altered pre-mRNA splicing and cell type differentiation via amino acid substitutions? If so, you are among many who appear to have been living under a rock for nearly two decades.

In 1996, we wrote: "Small intranuclear proteins also participate in generating alternative splicing techniques of pre-mRNA and, by this mechanism, contribute to sexual differentiation in at least two species..."

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