Summary: Researchers have identified a surprising link between blood circulation and the movement of newly formed neurons in the adult brain. Using advanced imaging in mice, the team found that neuron migration is faster along blood vessels with higher blood flow, and that the hunger hormone ghrelin amplifies this migration by activating internal cell movement. Calorie restriction, which raises blood ghrelin levels, further accelerated migration to the olfactory bulb. These results reveal how vascular dynamics and metabolic signals shape neuroregeneration and point to potential strategies for treating stroke and neurodegenerative disorders.
This study demonstrates that blood flow and circulating hormones work together to guide neuronal migration in the adult mammalian brain, with implications for olfactory function and recovery after brain injury.
Key Facts
- Flow-driven migration: New neurons travel faster along blood vessels that carry stronger blood flow.
- Hormonal modulation: Ghrelin, a hormone elevated by hunger, enhances neuronal movement by stimulating cytoskeletal activity.
- Therapeutic promise: Understanding blood flow–dependent migration could inform treatments for stroke, vascular dementia, and other neurological conditions.
Source: eLife
Researchers have discovered how newly generated neurons rely on blood flow to reach their destinations in the adult brain.
Published in eLife, the study by Takashi Ogino, Akari Saito and colleagues provides strong experimental evidence that newly formed neurons in the rostral migratory stream (RMS) align closely with blood vessels and that their migration speed correlates with the amount of blood flow along those vessels.
Adult neurogenesis involves the birth of new neurons that must migrate from their origin to their functional locations. In rodents, many neurons born in the subventricular zone (SVZ) travel along the RMS to the olfactory bulb, a structure responsible for processing smell. Previous work showed that blood vessels can act as scaffolds for migrating cells, but it remained unclear whether blood flow itself directly influences migration dynamics.
To clarify this, the research team used high-resolution 3D imaging and two-photon laser scanning microscopy in adult mice (6–12 weeks old) to map the spatial relationship between new neurons and blood vessels and to measure the movement of neurons and red blood cells in real time. These methods allowed precise quantification of migration speed in different vascular environments.
Their imaging revealed that newborn neurons often travel in close contact with blood vessels along the entire migratory route, from the RMS to the granule cell layer (GCL) of the olfactory bulb. Notably, neurons associated with vessels exhibiting higher blood flow showed significantly greater maximum migration speeds than those along low-flow vessels. This observation supports a model in which circulation not only provides physical guidance but also promotes neuronal migration.
The team then investigated whether blood-borne factors contribute to this effect. They focused on ghrelin, a hormone known to increase with hunger and circulate in the bloodstream. Fluorescently labeled ghrelin administered into the circulation accumulated in vascular endothelial cells and in parenchymal tissue of the RMS and olfactory bulb, demonstrating that ghrelin crosses the vascular wall and reaches newly born neurons.
Functional experiments showed that ghrelin signaling promotes somal translocation—the step in which the neuron’s cell body moves forward—by activating contraction of the actin cytoskeleton at the rear of the soma. This cytoskeletal activation provides a mechanistic explanation for how ghrelin enhances migration speed.
To test physiological relevance, authors examined the effect of calorie restriction, a condition known to elevate circulating ghrelin. Mice subjected to controlled calorie reduction exhibited increased migration of neurons to the olfactory bulb, consistent with ghrelin-mediated enhancement of neuronal movement. The authors suggest this mechanism may improve olfactory sensitivity for food-seeking during hunger.
The study also indicates that other blood-derived factors, in addition to ghrelin, might support vessel-guided migration. Blood flow inhibition reduced vessel-associated migration, implying that circulation delivers beneficial molecules that help cells move. Identifying these factors could open new avenues for therapies that harness blood flow or circulating signals to promote repair after stroke or slow degeneration in vascular dementia.
Key Questions Answered:
Q: How does blood flow affect the migration of new neurons?
A: Neurons migrate more rapidly along vessels with stronger blood flow, indicating that circulation directly supports their movement through brain tissue.
Q: What role does the hormone ghrelin play in this process?
A: Ghrelin crosses from the bloodstream into brain tissue, accumulates near migrating neurons, and activates actin-mediated somal translocation to speed migration.
Q: Why does this discovery matter?
A: It reveals that metabolic signals and vascular dynamics collectively regulate brain regeneration, suggesting new strategies to boost recovery after injury and to treat neurovascular conditions.
About this neuroscience research news
Author: Emily Packer
Source: eLife
Contact: Emily Packer – eLife
Image: Image credited to Neuroscience News
Original Research: Open access. “Neuronal migration depends on blood flow in the adult mammalian brain” by Takashi Ogino et al., eLife.
Abstract
Neuronal migration depends on blood flow in the adult mammalian brain
Several cell types in animal tissues migrate along blood vessels, suggesting that blood flow could influence cell migration. This study shows that blood flow promotes migration of newly formed olfactory-bulb neurons in the adult brain. Migration is facilitated near vessels with abundant flow, and inhibiting blood flow reduces vessel-guided neuronal migration—implying that blood carries factors that support movement. The hormone ghrelin, which rises during hunger, directly affects neuronal migration by promoting somal translocation through activation of actin contraction at the rear of the soma. New neurons that reach and mature in the olfactory bulb contribute to odor detection, particularly for food-seeking. Calorie restriction increases neuronal migration, a process involving ghrelin signaling. These findings indicate that blood flow and blood-derived ghrelin work together to enhance neuronal migration in the adult brain, a mechanism that may improve olfactory-driven behaviors during starvation and that could inform blood flow–based therapeutic strategies for neurological disease.