Summary: Researchers identified a specific type of cell that sits on top of the brain’s smallest blood vessels that sense when their region of the brain is in need of energy.
Source: University of Maryland
When we smell hot dogs, it may trigger memories of backyard barbeques or attending baseball games during childhood. During this process, the areas of the brain that control smell and long-term memory are rapidly firing off impulses. To fuel these signals from neurons, the active brain regions need oxygen and energy in the form of blood sugar glucose, which is quickly delivered through blood vessels.
Now, University of Maryland School of Medicine’s researchers have discovered that a certain type of cell that sits on top of the brain’s smallest blood vessels senses when their brain region needs energy. When glucose levels are low, these cells signal blood vessels to dilate, increasing the blood flow regionally and allowing more energy to fuel that part of the brain.
These findings from experiments in mice were published on Dec. 27, 2022, in Cell Reports.
“These fluctuations in blood flow help direct the brain’s energy resources to support everyday functions,” said study leader Thomas Longden, PhD, Assistant Professor of Physiology at UMSOM. “As I am speaking now, the blood flow in my brain will be diverted to the language areas and the motor (or movement) areas that control my vocal cords to fuel these processes.”
In 2022, Dr. Longden’s laboratory showed that signals in the form of calcium—shaped by electrical impulses through the blood vessels—cause certain brain capillaries to relax controlling blood flow, through a paper published in Science Advances.
In their newest study, his team demonstrated that a specific type of cell located along the outside of the capillaries, known as pericytes, direct these electrical pulses based on their perception of local energy needs.
The researchers directly observed this process playing out in mouse brains using advanced microscopy, and then dissected out the capillaries with their attached pericytes. They then measured electrical signals given off by the pericytes when glucose levels were adjusted. They found that the pericytes rapidly generated electrical signals when the sugar levels were low, but not when the levels were high.
“If adequate energy is not supplied by the brain blood vessels to the neurons in a timely manner, there can be a mismatch of energy supply and demand. This causes the brain’s neurons to undergo stress, which can lead to impaired protein metabolism, changes in how the neurons fire, and even eventually cell death,” said study co-author Ashwini Hariharan, PhD, Postdoctoral Fellow in Physiology at UMSOM.
“This energetic failure in blood vessel function of the brain has been shown to occur during the aging process, in certain neurodegenerative diseases, like Alzheimer’s, and in stroke,” said Dean of UMSOM Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor.
Dr. Longden added, “By studying how this process functions normally, researchers may be able to gain further insight into what happens in aging or in neurodegenerative diseases, so they can develop better therapies.”
Funding: This study was funded by the National Institutes of Health’s National Institute on Aging and National Institute of Neurological Disorders and Stroke (1R01AG066645, 5R01NS115401, and 1DP2NS121347-01), the American Heart Association, and the D.C. Women’s Board.
About this neuroscience research news
Author: Vanessa McMains
Source: University of Maryland
Contact: Vanessa McMains – University of Maryland
Image: The image is credited to University of Maryland
Original Research: Open access.
“Brain capillary pericytes are metabolic sentinels that control blood flow through a KATP channel-dependent energy switch” by Ashwini Hariharan et al. Cell Reports
Abstract
Brain capillary pericytes are metabolic sentinels that control blood flow through a KATP channel-dependent energy switch
Highlights
- Focal activation of thin-strand pericyte KATP channels dilates the upstream arteriole
- Brain capillary thin-strand pericytes monitor local glucose levels
- A pericyte KATP channel energy switch couples glucose changes with hyperemia
- This pericyte electro-metabolic signaling may protect neuronal health and function
Summary
Despite the abundance of capillary thin-strand pericytes and their proximity to neurons and glia, little is known of the contributions of these cells to the control of brain hemodynamics.
We demonstrate that the pharmacological activation of thin-strand pericyte KATP channels profoundly hyperpolarizes these cells, dilates upstream penetrating arterioles and arteriole-proximate capillaries, and increases capillary blood flow.
Focal stimulation of pericytes with a KATP channel agonist is sufficient to evoke this response, mediated via KIR2.1 channel-dependent retrograde propagation of hyperpolarizing signals, whereas genetic inactivation of pericyte KATP channels eliminates these effects.
Critically, we show that decreasing extracellular glucose to less than 1 mM or inhibiting glucose uptake by blocking GLUT1 transporters in vivo flips a mechanistic energy switch driving rapid KATP-mediated pericyte hyperpolarization to increase local blood flow.
Together, our findings recast capillary pericytes as metabolic sentinels that respond to local energy deficits by increasing blood flow to neurons to prevent energetic shortfalls.
