(From left) Zhongxiao Fu, PhD, and Chia-Yi Kuan, MD, PhD
Microglia, so-called the third elements in the brain, after neurons and macroglia that include astrocytes and oligodendrocytes, are a mysterious and multi-tasking cell-type. Microglia are famous for their waste disposal and pro-inflammatory roles in disease conditions, but recent research suggest that microglia also have important homeostatic functions in healthy brains.
A new study led by Chia-Yi Kuan, MD, PhD, a professor in the Department of Neuroscience, shown in the photo on the right with Zhongxiao Fu, PhD, the study’s first author, revealed how microglia regulate the local blood flow responses to neural activity, a process called neurovascular coupling. The research was published in the journal Nature Communications.
It is well-known that neural excitation in the brain is coupled to a surge of blood flow to match the energy demand with blood and oxygen supply. This tight coupling is the basis of functional magnetic resonance imaging (fMRI) and involves the actions of many cell-types, including neurons, astrocytes, and the vascular endothelial plus mural cells. In this new study, Dr. Kuan’s team showed that microglia are also a critical contributor to this coupling and they do so via a nucleotidase called CD39, present on cell surface. CD39 initiates the breakdown of extracellular adenosine triphosphate (ATP), which is released as a co-transmitter in neural activation, into adenosine to promote vasodilation, while preventing neuronal hyper-excitation. Dr. Fu and the team showed that CD39 is predominantly expressed by microglia in the murine cerebral cortex, and when microglia are depleted or the activity of CD39 is inhibited, stimulation of the mouse whiskers fails to induce the ascent of extracellular adenosine or local blood flow in the contralateral somatosensory cortex. These and other findings in the new study collectively uncovered an important homeostatic function of microglia and showed the underlying mechanism.
“This study showed a positive effect of microglia on the brain blood flow, but we realized through this study that microglia also subdue the basal cerebral blood flow,” stated Dr. Kuan. “We are currently studying the mechanisms of the latter, since an imbalance of these opposite effects (or yin and yang) on cerebral blood flow may explain the clinical finding of cerebral blood flow and metabolism reduction in neurodegeneration, such as the Alzheimer’s disease.”
Other UVA investigators in the study include Jill Venton, PhD, Katia Sol-Church, PhD, Pankaj Kumar, PhD, and Ukpong Eyo, PhD.
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