Neurons and glial cells are like dance partners in the brain, coordinating moves that shape how signals flow and how excitable neurons become. Astrocytes, star-shaped glial cells, can reshape themselves in response to various conditions, including high blood pressure. But the "how" behind this shape-shifting has remained a mystery.
To crack the code, McGill University researchers turned to a classic model: rats fed a high-salt diet. In these animals, astrocytes in a key brain region, the hypothalamus, lose some of their branching structures. This change isn't just cosmetic. It's part of a larger story where salt sparks brain inflammation, which in turn raises blood pressure.
This association flips the script on hypertension. Long blamed on the kidneys and blood vessels, it now seems the brain might be a silent instigator, especially in cases where standard treatments fail.
The study, published in Neuron, suggests that targeting brain mechanisms could play a role in developing treatments for stubborn cases of high blood pressure.
"This is new evidence that high blood pressure can originate in the brain, opening the door for developing treatments that act on the brain," said Masha Prager-Khoutorsky, associate professor in McGill's Department of Physiology.
To mimic a junk-food-heavy human diet, researchers gave rats salty water, about 2% salt, similar to what you'd get from daily doses of bacon, instant noodles, and processed cheese.
This salty shift didn't just affect the body; it lit up the brain. Immune cells (microglia) swarmed around vasopressin-producing neurons (the ones that help regulate blood pressure), but curiously, left other brain regions untouched.
These microglia didn't just hang around; they got snippy. They trimmed away the astrocytic branches that normally cradle and regulate these neurons. With astrocytes out of the picture, glutamate, a key neurotransmitter, spilled into extrasynaptic zones, flipping on NMDA receptors and revving up vasopressin neuron activity.
The result? A surge in blood pressure.
But here's the twist: when scientists blocked this microglial pruning, the neurons calmed down, and so did the hypertension. This reveals microglia as unexpected conductors in the brain's blood pressure orchestra, fine-tuning neuron-glia interactions through astrocyte pruning.
Researchers were able to track these changes using cutting-edge brain imaging and lab techniques that only recently became available.
"The brain's role in hypertension has largely been overlooked, in part because it's harder to study," said Prager-Khoutorsky. "But with new techniques, we're able to see these changes in action."
The next plan for the researchers includes studying whether similar processes are involved in other forms of hypertension.
The study was published in the journal Neuron.
Source: McGill University
