Lifelong Neuronal Rebirth

Neuronal regeneration in the human adult brain is more widespread than previously thought. 

By | February 20, 2014

WIKIMEDIA, LIFE SCIENCE DATABASECertain neurons in the human striatum—a brain region involved in movement and cognition—are renewed throughout life, according to a study published today (February 20) in Cell. At one time, researchers thought that human neurons regenerated in fewer brain regions than in rodents and nonhuman primates. Now it appears that regenerated neurons simply show up in different brain regions in humans compared with other mammals—a findings that has potential implications for the origins of learning and other higher-order cognitive processes.

“New neurons are integrated in another part of the brain in humans,” said Jonas Frisén, a neuroscientist at the Karolinska Institute in Sweden and a coauthor of the paper. “There’s a unique pattern of neurogenesis in humans compared to other animals.”

“This is the clearest demonstration that [adult neurogenesis in the striatum] is happening in humans,” said Arnold Kriegstein, a developmental neurobiologist at the University of California, San Francisco, who was not involved in the study. “It reenergizes the notion that . . . in the future, it would be possible to harness these cells in some way to repair the injured brain.”

Previously, it had been shown that nonhuman mammals undergo adult neurogenesis in two brain regions: the hippocampus, which is involved in memory, and the olfactory bulb, which processes smells. Neuronal progenitor cells, or neuroblasts, destined for the olfactory bulb are born in the subventricular zone (SVZ) of the brain. Humans also produce neuroblasts in the SVZ, but these cells never make it to the olfactory bulb. Frisén and his colleagues hypothesized that, rather than heading to the olfactory bulb, human SVZ neuroblasts integrate in the nearby striatum.

“It is clear that we are much less dependent on olfaction—and have a less developed sense of smell—than most other mammals,” Frisén explained in an e-mail to The Scientist. “In contrast, we of course have much more advanced cognitive plasticity and adaptability, and it is tempting to consider the possibility that new neurons in the striatum may contribute to such functions.”

Frisén’s team used several techniques to determine whether neurons in the striatum were present from birth or arose during adulthood. First, the researchers analyzed published human brain transcriptome data, as well as postmortem brains, finding that markers of neuroblasts were elevated in the striata in brains of a various ages, as well as in the SVZ and hippocampus. The researchers also analyzed postmortem neurons for accumulation of lipofuscin, a pigment that builds up in neurons as they age. They found that cells with neuroblast-related markers tended to have little to no pigment buildup, confirming their newness.

The researchers also analyzed tissue from the brains of deceased cancer patients. Cancer patients are sometimes given iododeoxyuridine (IdU), a molecule that is incorporated into DNA, in an attempt to sensitize malignant cells to radiation therapy. The researchers found elevated IdU levels in parts of the striatum and the hippocampus, indicating that some cells in these brain regions had originated during cancer therapy.

Finally, the researchers analyzed postmortem brains using nuclear-bomb-test-derived 14C dating, a technique Frisén and colleagues pioneered around a decade ago. Above-ground nuclear testing proceeded rapidly in the 1950s and early 1960s, spewing 14C into the atmosphere. Following a ban of above-ground nuclear testing in 1963, concentrations of 14C have declined at a predictable rate. Assessing the concentration of 14C incorporated into genomic DNA can determine a cell’s time of birth. The 14C data from brains of a range of ages indicated that interneurons in the striatum were regularly replaced. Exceptions to this phenomenon were found in the postmortem brains of people who had advanced Huntington’s disease, a neurodegenerative disease affecting the striatum. These organs displayed few or no neurons in the striatum that were formed during adulthood.

Taken together, the team’s results are convincing, said Hongjun Song, a neuroscientist at Johns Hopkins University in Baltimore, Maryland. “They’re actually using many technologies which are not easy to do and they’ve done it in one study, which is quite extraordinary.”

Kriegstein suggested that researchers should next look more closely at neuronal renewal in the striata of other animals. “It will be important to take a look at the striatum of nonhuman primates, which presumably would have a similar thing going on in adulthood,” he said. If widespread neuronal regeneration in the striatum is found in experimental animals, they might prove to be fruitful tools for studying the phenomenon. If it turns out that neuronal replacement in the striatum shows a unique pattern in humans, it could help explain cognitive differences between humans and other species.

Eventually, Frisén and his colleagues’ findings could impact regenerative medicine research and the treatment of neurodegenerative diseases. Kriegstein noted that researchers might even manipulate the SVZ to produce a greater variety of cells than just striatal interneurons. Perhaps someday progenitor neurons produced in the SVZ could be prodded to migrate in various directions and repair a variety of brain injuries and degenerations.

For now, the researchers seek an improved understanding of striatal interneurons and the role adult neurogenesis might play in the function of the brain, Frisén said.

“I think it will be a very important study for the whole field,” said Song.

A. Ernst et al., “Neurogenesis in the striatum of the adult human brain,” Cell, doi:10.1016/j.cell.2014.01.044, 2014.

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Avatar of: James V. Kohl

James V. Kohl

Posts: 194

February 22, 2014

The perceptual logic of smell "...growing recent evidence for expression of olfactory receptors in non-chemosensory tissue" implies that "..the complexity of the olfactory genome may hold secrets for more than understanding olfaction alone."

This model details how chemical ecology drives adaptive evolution via: (1) ecological niche construction, (2) social niche construction, (3) neurogenic niche construction, and (4) socio-cognitive niche construction. This model exemplifies the epigenetic effects of olfactory/pheromonal conditioning, which alters genetically predisposed, nutrient-dependent, hormone-driven mammalian behavior and choices for pheromones that control reproduction via their effects on luteinizing hormone (LH) and systems biology.

Pheromones and the luteinizing hormone for inducing proliferation of neural stem cells and neurogenesis links my atoms to ecosystems approach from food odors and pheromones to neurogenic niche construction, neurodegenerative diseases and to morphological and behavioral phenotypes in species from roundworms to humans. 

For example, see: System-wide Rewiring Underlies Behavioral Differences in Predatory and Bacterial-Feeding Nematodes "We uncover a massive rewiring in a complex system of identified neurons, all of which are homologous based on neurite anatomy and cell body position."

No experimental evidence suggests that "...we are much less dependent on olfaction—and have a less developed sense of smell—than most other mammals...." That is an ecologically invalidated opinion, which Dr. Frisen's work helps to expose in the context of neurogenic niche construction.

It is also an opinion that is biologically implausible. Like other opinions about cause and effect, it must be placed into the context of the ecological adaptations that enable neurogenic niche construction. Clearly, we cannot be any less dependent on olfaction for nutrient acquisition or the nutrient-dependent pheromone-controlled physiology of our reproduction than any other organism with conserved molecular mechanisms. And those mechanisms link the epigenetic landscape to the physical landscape of DNA in the organized genomes of species from microbes to man.

In that context, opinions about the relative salience of different types of sensory input, which epigenetically effect the molecular mechanisms that affect behavior, and opinions about the primacy of our sense of smell defy The perceptual logic of smell. Ernst et al., tells us it is time for our opinions to become acquainted with biological facts.

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