Oligodendroglial Progenitor Cells Suddenly Sprout Neurons!

The study identified the new pyramidal neurons in a part of the brain not typically associated with neurogenesis, the piriform cortex. The piriform cortex receives not only olfactory information, but also inputs from regions of the brain that are involved in emotion regulation and memory formation. Because of its privileged access to diverse brain regions, the piriform cortex is capable of tying odor representations to other types of information that are important for a wide range of behaviors. In animals and humans, activation in the piriform cortex is linked to odor memory and the emotional qualities of odors. In rodents, activity in this region is related to sexual behavior. _HND

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Scientists from UC Davis have discovered that neurons are being created from non-neuron progenitor cells in the brains of mice in early adulthood. These new neurons can apparently go on to play an important role in transmitting signals to "widespread" parts of the brain.

"We used to think that the sole destiny of oligodendroglial progenitor cells was to become myelin-forming oligodendroglia," Pleasure said. "Later it was shown that they also can generate other kinds of glial cells as well. We now have demonstrated that these oligodendroglial progenitor cells, which are widely distributed in the brain, and persist throughout life, also give rise to a group of large cerebral cortical neurons. Thus, oligodendroglial progenitor cells are truly multipotent."

The researchers found that precursors of glial cells, called proteolipid promoter-expressing NG2 progenitors (PPEPs, pronounced Pee-peps), give rise to glutamatergic pyramidal neurons, an important type of brain cell that sends long-range excitatory signals. PPEPs belong to a class of glial precursor cells called oligodendroglial progenitor cells (OPCs). These cells have been discovered only recently, and they hold tremendous promise for stem-cell regenerative medicine. They are the largest proliferating population of cells in the mammalian brain and spinal cord, and they could replace or repair injured cells.

“This study shows very definitively that PPEPs generate new neurons, that these new neurons have all the morphological and structural features which suggest that they are functionally integrated into the existing circuitry,” said Fuzheng Guo, the study’s lead author and a postdoctoral fellow in the Department of Neurology in the UC Davis School of Medicine.

...The current study follows findings published in 2009 that PPEPs in the immature mouse brain generate neurons in multiple regions, including the hippocampus and piriform cortex, and that these neurons survive into adulthood. They also found that PPEPs produced GABA-ergic interneurons in the immature brain. Prior to that study, scientists had assumed that the general class of glial precursor cells, called oligodendroglial progenitor cells (OPCs), could produce only glial cells, which create insulating sheets that wrap around neuronal projections and ensure speedy and reliable signal transmission. Instead, their results showed that these cells generate all three major cell types in the brain and spinal cord.

“Whether or not OPCs could form new neurons was not at all clear until our prior study,” Pleasure said.

The researchers focused on the piriform cortex in the current study because it was found to be a “hot spot” for PPEPs in the earlier study. The study was conducted using a genetic fate-mapping technique to track the lineage, or cell fates, of OPCs in the young adult brains of genetically-engineered mice. _HND

The study was in mice, but if similar mechanisms are at play in late adolescent and early adult humans, they might explain more of the differences between the adolescent and the adult brain.

We know that pathways of the brain develop over time, and that full maturation and myelinisation does not complete until the mid-twenties or slightly later. Late development of the pre-frontal cortex is probably part of the explanation for emotional and mental maturation in adulthood, but the development in early adulthood of new pathways involved in memory formation, emotional regulation, and sexual behaviours -- as described in the above study -- may provide deeper explanations into human emotional maturation.

Scientists will now have to look more carefully -- cast a wider net -- to try to understand the many nuances of brain development and the origination of new neurons and neuronal pathways. A few new answers, a lot of new questions.