title: Pericyte degeneration leads to neurovascular uncoupling and limits oxygen supply to brain.
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.
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Kassandra
authors.initials: K
authors.lastname: Kisler
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Nelson
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Sanket V
authors.initials: SV
authors.lastname: Rege
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Anita
authors.initials: A
authors.lastname: Ramanathan
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Yaoming
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Ashim
authors.initials: A
authors.lastname: Ahuja
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.|Department of Neurobiology, Institute for Biological Research, University of Belgrade, Belgrade, Republic of Serbia.
authors.forename: Divna
authors.initials: D
authors.lastname: Lazic
authors.affiliation: Department of Physics, University of California, San Diego, La Jolla, California, USA.
authors.forename: Philbert S
authors.initials: PS
authors.lastname: Tsai
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Shapingba District, Chongqing, China.
authors.forename: Yi
authors.identifier: http://orcid.org/0000-0002-2623-8960
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Boas
authors.affiliation: Optics Division, Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
authors.forename: Sava
authors.initials: S
authors.lastname: Sakadžić
authors.affiliation: Department of Physiology and Biophysics and the Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, California, USA.
authors.forename: Berislav V
authors.identifier: http://orcid.org/0000-0002-6802-8232
authors.initials: BV
authors.lastname: Zlokovic
mesh_terms: D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000378:metabolism; D002196:Capillaries / Q000502:physiology; D016923:Cell Death / Q000502:physiology*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology; D010100:Oxygen / Q000378:metabolism*; D020286:Pericytes / Q000473:pathology*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics; D013312:Stress, Physiological / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D018398:Homeodomain Proteins; C484194:Meox2 protein, mouse; D020797:Receptor, Platelet-Derived Growth Factor beta; D010100:Oxygen