Interpericyte tunnelling nanotubes regulate neurovascular coupling

Alarcón-Martínez, Luis; Villafranca‐Baughman, Deborah; Quintero, Heberto; Kacerovsky, J. Benjamin; Dotigny, Florence; Murai, Keith K.; Prat, Alexandre; Drapeau, Pierre; Polo, Adriana Di

doi:10.1038/s41586-020-2589-x

Cited by 202 publications

(181 citation statements)

References 26 publications

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“…However, the precise signals transported between cells via these bridges has not yet been explored. In another more recent study, Di Polo and colleagues identified TNT‐like processes (termed interpericyte TNTs or IP‐TNTs) that connect pericytes on retinal capillaries and form a functional syncytium (Alarcon‐Martinez et al , 2020). The authors show that IP‐TNTs contain mitochondria and actin, and propagate intercellular calcium waves; however, their close‐ended tip characterized by the presence of GJs may limit the intercellular transport of larger cargoes (Zurzolo, 2020).…”

Section: An Overview Of Tunneling Nanotubesmentioning

confidence: 99%

Peering into tunneling nanotubes—The path forward

Cervantes

Zurzolo

2021

The EMBO Journal

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The identification of Tunneling Nanotubes (TNTs) and TNT‐like structures signified a critical turning point in the field of cell‐cell communication. With hypothesized roles in development and disease progression, TNTs’ ability to transport biological cargo between distant cells has elevated these structures to a unique and privileged position among other mechanisms of intercellular communication. However, the field faces numerous challenges—some of the most pressing issues being the demonstration of TNTs in vivo and understanding how they form and function. Another stumbling block is represented by the vast disparity in structures classified as TNTs. In order to address this ambiguity, we propose a clear nomenclature and provide a comprehensive overview of the existing knowledge concerning TNTs. We also discuss their structure, formation‐related pathways, biological function, as well as their proposed role in disease. Furthermore, we pinpoint gaps and dichotomies found across the field and highlight unexplored research avenues. Lastly, we review the methods employed to date and suggest the application of new technologies to better understand these elusive biological structures.

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Section: An Overview Of Tunneling Nanotubesmentioning

confidence: 99%

Peering into tunneling nanotubes—The path forward

Cervantes

Zurzolo

2021

The EMBO Journal

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“…Additionally, teriflunomide improves pericyte coverage and survival, resulting in decreased TJ protein breakdown and BBB leakage 108 . A recent study has shown that novel interpericyte tunneling nanotubes could build a functional network to regulate neurovascular coupling through linking two separate PCs on different capillaries in the mouse retina 109 …”

Section: Is Therapies Targeting the Nvumentioning

confidence: 99%

Neurovascular Unit: A critical role in ischemic stroke

et al. 2021

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Ischemic stroke (IS), a common cerebrovascular disease, results from a sudden blockage of a blood vessel in the brain, thereby restricting blood supply to the area in question, and making a significantly negative impact on human health. Unfortunately, current treatments, that are mainly based on a recanalization of occluded blood vessels, are insufficient or inaccessible to many stroke patients. Recently, the profound influence of the neurovascular unit (NVU) on recanalization and the prognosis of IS have become better understood; in‐depth studies of the NVU have also provided novel approaches for IS treatment. In this article, we review the intimate connections between the changes in the NVU and IS outcomes, and discuss possible new management strategies having practical significance to IS. We discuss the concept of the NVU, as well as its roles in IS blood‐brain barrier regulation, cell preservation, inflammatory immune response, and neurovascular repair. Besides, we also summarize the influence of noncoding RNAs in NVU, and IS therapies targeting the NVU. We conclude that both the pathophysiological and neurovascular repair processes of IS are strongly associated with the homeostatic state of the NVU and that further research into therapies directed at the NVU could expand the range of treatments available for IS.

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“…Additionally, another transcriptomic study indicates that there are three pericyte subtypes with type 1 being the most numerous throughout the brain while type 3 pericytes are more similar to vascular smooth muscle cells, as per their respective expression profiles (Zeisel et al, 2018). To complicate things further, studies continue to demonstrate that pericytes, even capillary pericytes, may also have vasomotor functions to regulate cerebral blood flow and neurovascular coupling (Alarcon-Martinez et al, 2020;Nelson et al, 2020). Recently, a pericyte-specific mouse model was developed using a double promoter method to exclusively label pericytes and to highlight the catastrophic effects of pericyte ablation (Nikolakopoulou et al, 2019).…”

Section: Regional Differences Of the Pericyte And Associated Vulnerabmentioning

confidence: 99%

Pericytes Across the Lifetime in the Central Nervous System

Bennett

Kim

2021

Front. Cell. Neurosci.

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The pericyte is a perivascular cell type that encapsulates the microvasculature of the brain and spinal cord. Pericytes play a crucial role in the development and maintenance of the blood-brain barrier (BBB) and have a multitude of important functions in the brain. Recent evidence indicates that pericyte impairment has been implicated in neurovascular pathology associated with various human diseases such as diabetes mellitus, Alzheimer’s disease (AD), and stroke. Although the pericyte is essential for normal brain function, knowledge about its developmental trajectory and anatomical distribution is limited. This review article summarizes the scientific community’s current understanding of pericytes’ regional heterogeneity in the brain and their changes during major life stages. More specifically, this review article focuses on pericyte differentiation and migration during brain development, regional population differences in the adult brain, and changes during normal and pathological aging. Most of what is known about pericytes come from studies of the cerebral cortex and hippocampus. Therefore, we highlight the need to expand our understanding of pericyte distribution and function in the whole brain to better delineate this cell type’s role in the normal brain and pathological conditions.

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Interpericyte tunnelling nanotubes regulate neurovascular coupling

Cited by 202 publications

References 26 publications

Peering into tunneling nanotubes—The path forward

Peering into tunneling nanotubes—The path forward

Neurovascular Unit: A critical role in ischemic stroke

Pericytes Across the Lifetime in the Central Nervous System

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