F-actin polymerization contributes to pericyte contractility in retinal capillaries

Küreli, Gülce; Yilmaz-Ozcan, Sinem; Erdener, Şefik Evren; Dönmez-Demir, Buket; Yemişçi, Müge; Karataş, Hülya; Dalkara, Turgay

doi:10.1016/j.expneurol.2020.113392

Cited by 29 publications

(33 citation statements)

References 37 publications

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“…Although the functional diversity across compartments seems surprising, put in the context of the literature, it is similar to the anatomical diversity which has been described by other groups, in which branch order transition points in the expression of proteins such as smooth-muscle actin can vary across different vascular arbors 8,9,17,18 . Here the purpose of our work was to examine the degree of stereotypy and/or diversity in the timing of compartmentalized functional responses across the vascular arbor, and not add to the controversy over whether capillaries actively dilate which is in part an issue of semantics.…”

Section: Discussionsupporting

confidence: 59%

Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex

et al. 2021

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The spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.

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Section: Discussionsupporting

confidence: 59%

Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex

et al. 2021

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“… 20 However, little to no smooth muscle actin expression ( acta1 , acta2, actg2, actc1 ) is detected, making the binding partner of the myosin proteins unclear. In retina, recent studies have shown that α-SMA and F-actin polymerization are involved in contraction of capillary pericytes 44 , 45 and that immunohistochemical detection of low-level α-SMA requires specialized fixation procedures. 46 Therefore, it is possible that acta2 /α-SMA expression is simply low and difficult to detect in capillary pericytes, yet sufficient in quantity to support slow actomyosin contraction.…”

Section: Discussionmentioning

confidence: 99%

Brain capillary pericytes exert a substantial but slow influence on blood flow

et al. 2021

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The majority of the brain’s vasculature is comprised of intricate capillary networks lined by capillary pericytes. However, it remains unclear whether capillary pericytes influence blood flow. Using two-photon microscopy to observe and manipulate brain capillary pericytes in vivo , we find that their optogenetic stimulation decreases lumen diameter and blood flow, but with slower kinetics than similar stimulation of mural cells on upstream pial and pre-capillary arterioles. This slow vasoconstriction was inhibited by the clinically-used vasodilator fasudil, a Rho-kinase inhibitor that blocks contractile machinery. Capillary pericytes were also slower to constrict back to baseline following hypercapnia-induced dilation, and slower to dilate towards baseline following optogenetically-induced vasoconstriction. Optical ablation of single capillary pericytes led to sustained local dilation and a doubling of blood cell flux selectively in capillaries lacking pericyte contact. These data indicate that capillary pericytes contribute to basal blood flow resistance and slow modulation of blood flow throughout the brain.

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“…Additionally, changes in the polymerization status of cytoskeletal F-actin and α-SMA were proposed to regulate the stiffness and contractility of mid-capillary pericytes (Kureli et al, 2020). Future studies are still required to decipher this ongoing key issue.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent papers have proposed that pericytes may use alternative contractile proteins (Nelson et al., 2020; Hartmann et al, 2020 Preprint) expressed by them as determined by transcriptomic studies (He et al., 2018; Vanlandewijck et al., 2018). Additionally, changes in the polymerization status of cytoskeletal F‐actin and α‐SMA were proposed to regulate the stiffness and contractility of mid‐capillary pericytes (Kureli et al., 2020). Future studies are still required to decipher this ongoing key issue.…”

Section: Discussionmentioning

confidence: 99%

A nuclear fluorescent dye identifies pericytes at the neurovascular unit

Mai‐Morente

Marset

Blanco

et al. 2020

Journal of Neurochemistry

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Perivascular pericytes are key regulators of the blood-brain barrier, vascular development, and cerebral blood flow. Deciphering pericyte roles in health and disease requires cellular tracking; yet, pericyte identification remains challenging. A previous study reported that the far-red fluorophore TO-PRO-3 (642/661), usually employed as a nuclear dye in fixed tissue, was selectively captured by live pericytes from the subventricular zone. Herein, we validated TO-PRO-3 as a specific pericyte tracer in the nervous system (NS). Living pericytes from ex vivo murine hippocampus, cortex, spinal cord, and retina robustly incorporated TO-PRO-3. Classical pericyte immunomarkers such as chondroitin sulphate proteoglycan neuron-glial antigen 2 (NG2) and platelet-derived growth factor receptor beta antigen (PDGFrβ) and the new pericyte dye NeuroTrace 500/525 confirmed cellular specificity of dye uptake.The TO-PRO-3 signal enabled quantification of pericytes density and morphometry; likewise, TO-PRO-3 labeling allowed visualization of pericytes associated with other components of the neurovascular unit. A subset of TO-PRO-3 stained cells expressed the contractile protein α-SMA, indicative of their ability to control the capillary diameter. Uptake of TO-PRO-3 was independent of connexin/pannexin channels but was highly sensitive to temperature and showed saturation, suggesting that a yet unidentified protein-mediated active transport sustained dye incorporation. We conclude that TO-PRO-3 labeling provides a reliable and simple tool for the bioimaging of pericytes in the murine NS microvasculature.

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F-actin polymerization contributes to pericyte contractility in retinal capillaries

Cited by 29 publications

References 37 publications

Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex

Diversity of neurovascular coupling dynamics along vascular arbors in layer II/III somatosensory cortex

Brain capillary pericytes exert a substantial but slow influence on blood flow

A nuclear fluorescent dye identifies pericytes at the neurovascular unit

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