Scientists have discovered why a select few newborn neurons survive, while most die before they can help with cognition, memory, or the regulation of mood.
The findings have wide implications for people with neurodegenerative conditions, such as dementia or Alzheimer’s disease, and perhaps for patients with brain damage, researchers say.
Published in the journal, Nature Neuroscience, the new study shows how specific brain cells communicate with each other during adult neurogenesis—the creation of new neurons. One cell type—PV+ interneurons—can be stimulated to help baby neurons survive and thrive even as older neurons die.
“We now know how newborn neurons can be regenerated in specific regions of the brain,” says Juan Song, assistant professor of pharmacology at the University of North Carolina at Chapel Hill and the UNC Neuroscience Center.
“By showing how interneurons are a part of neurogenesis, we can see how it’s possible to regenerate cells in parts of the brain that are damaged, for example, because of a stroke.”
Neurogenesis, which occurs throughout the brain during pre-natal development, continues throughout adulthood in just two brain regions—the hippocampus and subventricular zone.
Neurons grow up
It works like this: neural stem cells produce progenitor cells, more than half of which die within four days. The progenitor cells don’t have axons or dendrites—the cell parts that adult neurons use to create and transmit signals to each other.
The surviving progenitor cells—also known as newborn or baby neurons—then turn into immature neurons; these do form axons and dendrites and evolve into mature neurons that connect with other neurons through synapses. These mature neurons then integrate into the complex neural networks involved in cognition, memory, and mood.
Previously, when Song was a postdoctoral fellow at Johns Hopkins University, she studied how stem cells create neurons. She showed how neural stem cells “sense” the transmission of chemical signals between mature neurons and PV+ interneurons.
Song’s team used words such as “sensed,” “listened,” and “eavesdropped” because they found that the stem cells did not form synaptic connections with either the mature neurons or the interneurons.
They somehow “heard” the chemical signaling between the two other cell types. And depending on the signal, the stem cells either stayed dormant or began creating progenitor cells.
Because Song found that the stem cells weren’t physically connected to interneurons or mature neurons, she thought that the stem cell progeny—the newborn neurons—might also “sense” the chemical communication between mature neurons and interneurons.
But that’s not what she found.
Using mouse models and electron microscopy, Song discovered that PV+ interneurons attach their tail-like axons to newborn progenitor cells to form a synapse. Across that synaptic connection, the interneurons send chemical signals.
When Song stimulated the interneurons with a beam of light or mild electrical signals, the baby neurons lived longer than they did without stimulation.
“The progenitors survived,” Song says. “They evolved into new neurons. So, this stimulation created more neurogenesis in the adult brains of mice.”
Role of exercise
It’s unclear how such stimulation translates into human activity. For instance, exercise has been found to trigger the creation of neurons in mice. And exercise in adults has shown to improve brain function.
But it isn’t clear that the creation of new neurons always causes improved brain function. Also, it isn’t clear that the lack of exercise—both physical and perhaps cognitive—slows down neurogenesis as we age.
Still, Song’s research is the first to show that simulating a specific cell type does indeed spur on neurogenesis. The finding underscores the importance of a specific cell type—PV+ interneurons—in the creation of new neurons, and it offers researchers another route to finding therapies for degenerative conditions and even brain disorders, such as schizophrenia.
“I think our study could be extended to look directly at behaviors in mouse models of neurological diseases. We would be able to see if behaviors are linked to interneurons and neurogenesis.”
For now, Song’s lab is still uncovering the mysteries of neurogenesis in normal animal models. For instance, scientists aren’t sure exactly how stem cells “sense” the communication between interneurons and mature neurons.
They also don’t know if simply stimulating interneurons causes stem cells to give birth to progenitor cells or if something more complicated is going on. Song is studying that now.
Her team also wants to study exactly how interneurons become attached to progenitor cells; how do interneurons “find” the baby neurons to communicate with them?
“Right now, we don’t know. Our working hypothesis is that new neurons are born into a mesh of interneuron terminals. And we think the newborn neurons possess chemical signals that guide the interneurons, which then attach to the newborn neurons.
“It would be interesting to see if the newborn neurons that lack this synaptic connection are the same ones that die before becoming mature neurons.”
Source: UNC-Chapel Hill