Pericytes are essential for normal brain function, but many aspects of their physiology remain enigmatic due to a lack of tools to genetically target this cell population. Here, we characterize brain pericytes using two existing Cre-recombinase driver mouse lines that can serve distinct purposes in cerebrovascular research. One line expresses an inducible version of Cre under the NG2 proteoglycan promoter, which provides the sparse labeling necessary to define the morphology of single cells. These mice reveal structural differences between pericytes adjacent to arterioles versus those broadly distributed in the capillary bed that may underlie differential roles in control of vessel caliber. A second line expresses Cre constitutively under the platelet-derived growth factor receptor β promoter and provides continuous, highly specific and near-complete labeling of pericytes and myocytes along the entire cerebrovasculature. This line provides a three-dimensional view of pericyte distribution along the cortical angioarchitecture following optical clearing of brain tissue. In combination with recent reporter lines for expression of optogenetic actuators and activity-sensitive probes, these mice may be key tools for studying pericyte biology in the intact brain.
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http://dx.doi.org/10.1117/1.NPh.2.4.041402 | DOI Listing |
J Biosci Bioeng
December 2024
Institute of Frontier Science and Technology, Okayama University of Science, Okayama 700-0005, Japan. Electronic address:
Vascular-like tissues composed of cells maintaining their shape and structure at any position in a culture dish without the use of gels or other artificial materials are ideal vascular models to test the effects of candidate drugs on cells without adsorption by artificial materials and analysis of structural changes over time. In this study, we aimed to prepare fiber-shaped cell aggregates composed of human umbilical vein endothelial and mesenchymal stem cells as vascular pericytes anchored to the bottom of culture dishes at a defined location using our developed cell self-aggregation technique and dumbbell-shaped culture groove. The fiber-shaped cell aggregates maintained their shape for at least two weeks without rupture, and histological analysis revealed that they formed a unique tissue structure with a gapless endothelial layer on the outer surface and capillary-like structures oriented in the same direction as the long axis of the fiber in the medial side.
View Article and Find Full Text PDFBiophys J
December 2024
Department of Pharmacology, Larner College of Medicine, Vermont Center for Cardiovascular and Brain Health, University of Vermont, Burlington, VT, 05405, USA. Electronic address:
Amyloid-beta (Aβ) peptide accumulation on blood vessels in the brain is a hallmark of neurodegeneration. While Aβ peptides constrict cerebral arteries and arterioles, their impact on capillaries is less understood. Aβ was recently shown to constrict brain capillaries through pericyte contraction, but whether-and if so how-Aβ affects endothelial cells (ECs) remains unknown.
View Article and Find Full Text PDFNeurobiol Dis
December 2024
Department of Neurology, China-Japan Union Hospital of Jilin University, No. 126 Xiantai Street, Changchun 130031, Jilin, China.. Electronic address:
Vascular cognitive impairment (VCI) is a progressive cognitive impairment caused by cerebrovascular disease or vascular risk factors. It is the second most common type of cognitive impairment after Alzheimer's disease. The pathogenesis of VCI is complex, and neurovascular unit destruction is one of its important mechanisms.
View Article and Find Full Text PDFCurr Biol
December 2024
Synaptic Physiology Section, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, MD 20814, USA. Electronic address:
The neurovascular unit (NVU), comprising vascular, glial, and neural elements, supports the energetic demands of neural computation, but this aspect of the retina's trilaminar vessel network is poorly understood. Only the innermost vessel layer-the superficial vascular plexus (SVP)-is associated with astrocytes, like brain capillaries, whereas radial Müller glia interact with vessels in the other layers. Using serial electron microscopic reconstructions from mouse and primate retina, we find that Müller processes cover capillaries in a tessellating pattern, mirroring the wrapping of brain capillaries by tiled astrocytic endfeet.
View Article and Find Full Text PDFMetab Brain Dis
December 2024
Institute of Neurology (Edinger Institute), University Hospital, Goethe University Frankfurt, Frankfurt am Main, Germany.
The blood-brain barrier (BBB) is formed by microvascular endothelial cells which are ensembled with pericytes, astrocytes, microglia and neurons in the neurovascular unit (NVU) that is crucial for neuronal function. Given that the NVU and the BBB are highly dynamic and regulated structures, their integrity is continuously challenged by intrinsic and extrinsic factors. Herein, factors from peripheral organs such as gonadal and adrenal hormones may influence vascular function also in CNS endothelial cells in a sex- and age-dependent manner.
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