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Nat Neurosci. 2017 Mar;20(3):406-416. doi: 10.1038/nn.4489. Epub 2017 Jan 30.

Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain.

Author information

1
Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
2
Department of Neurobiology, Institute for Biological Research, University of Belgrade, Belgrade, Republic of Serbia.
3
Department of Physics, University of California, San Diego, La Jolla, California, USA.
4
Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Shapingba District, Chongqing, China.
5
Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.

Abstract

Pericytes are perivascular mural cells of brain capillaries. They are positioned centrally in the neurovascular unit between endothelial cells, astrocytes and neurons. This position allows them to regulate key neurovascular functions of the brain. The role of pericytes in the regulation of cerebral blood flow (CBF) and neurovascular coupling remains, however, under debate. Using loss-of-function pericyte-deficient mice, here we show that pericyte degeneration diminishes global and individual capillary CBF responses to neuronal stimuli, resulting in neurovascular uncoupling, reduced oxygen supply to the brain and metabolic stress. Neurovascular deficits lead over time to impaired neuronal excitability and neurodegenerative changes. Thus, pericyte degeneration as seen in neurological disorders such as Alzheimer's disease may contribute to neurovascular dysfunction and neurodegeneration associated with human disease.

PMID:
28135240
PMCID:
PMC5323291
DOI:
10.1038/nn.4489
[Indexed for MEDLINE]
Free PMC Article

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