A Role for Pericyte Dysfunction in Neurodegenerative Conditions

Researchers here investigate dysfunction of the class of cells known as pericytes that surround small blood vessels. These cells regulate blood flow, and in the brain support the blood-brain barrier, among other activities. Like all aspects of our cellular machinery, pericytes suffer damage, reduced function, and greater levels of cell death with advancing age. The open question, as is usually the case, is where this fits in the lengthy chain of of cause and consequence that leads from fundamental cellular damage and waste accumulation of the types outlined in the SENS rejuvenation research materials to specific age-related disease and disability.

A new study is the first to use a pericyte-deficient mouse model to test how blood flow is regulated in the brain. The goal was to identify whether pericytes could be an important new therapeutic target for treating neuron deterioration. "Pericyte degeneration may be ground zero for neurodegenerative disorders like Alzheimer's disease, ALS and possibly others. A glitch with gatekeeper cells that surround capillaries may restrict blood and oxygen supply to active areas of the brain, gradually causing neuron loss that might have important implications for Alzheimer's disease. Vascular problems increase the risk of cognitive impairment in many types of dementia, including Alzheimer's disease. Pericytes play an important part in keeping your brain healthy."

To test the theory, researchers stimulated the hind limb of young mice deficient in gatekeeper cells and monitored the global and individual responses of brain capillaries, the smallest blood vessels in the brain. The global cerebral blood flow response to an electric stimulus was reduced by about 30 percent compared to normal mice, denoting a weakened system. Relative to the control group, the capillaries of pericyte-deficient mice took 6.5 seconds longer to dilate. Slower capillary widening and a slower flow of red blood cells carrying oxygen through capillaries means it takes longer for the brain to get its fuel. As the mice turned 6 to 8 months old, global cerebral blood flow responses to stimuli progressively worsened. Blood flow responses for the experimental group were 58 percent lower than that of their age-matched peers. In short, with age, the brain's malfunctioning vascular system exponentially worsens.

"We now understand the function of blood vessel gatekeeper cells is to ensure adequate oxygen and energy supply to brain cells. Prior to our study, scientists knew patients with Alzheimer's disease, ALS and other neurodegenerative disorders experience changes to the blood flow and oxygen being supplied to the brain and that pericytes die. Our study adds a new piece of information: Loss of these gatekeeper cells leads to impaired blood flow and insufficient oxygen delivery to the brain. The big mystery now is: What kills pericytes in Alzheimer's disease?" Scientists are already working to further this line of research, scanning the brains of people who are genetically at risk for Alzheimer's. They are also collecting cerebral spinal fluid and blood for analysis of vascular damage, including injury to pericytes.

Link: http://news.usc.edu/115566/a-glitch-in-gatekeeper-cells-slowly-suffocates-the-brain/

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