Genetic dissection of the neuro-glio-vascular machinery in the adult brain

Kirschen, Gregory W.; Kery, Rachel; Liu, Hanxiao; Ahamad, Afrinash; Chen, Liang; Akmentin, Wendy; Kumar, Ramya; Levine, Joel M.; Xiong, Qiaojie; Ge, Shaoyu

doi:10.1186/s13041-017-0345-4

Cited by 8 publications

(8 citation statements)

References 65 publications

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“…Likewise, both astrocytes and RGL cells of the dentate gyrus contact the vasculature via their fine processes [ 41, 42 ]. The functional significance of these vascular contacts remains uncertain, but those of RGL cells seem to guide fate specification and proliferation of progenitor cells via hematogenously-derived cues, while those of astrocytes may link hippocampal glucose metabolism to glutamatergic synaptic transmission at the doublecortin (DCX) stage [ 39, 43, 44 ].…”

Section: The Anatomical Formation Of Hippocampal Vasculature Neuronsmentioning

confidence: 99%

The Hippocampal Neuro-Glio-Vascular Network: Metabolic Vulnerability and Potential Neurogenic Regeneration in Disease

Kirschen

Kery

2018

BPL

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Brain metabolism is a fragile balance between nutrient/oxygen supply provided by the blood and neuronal/glial demand. Small perturbations in these parameters are necessary for proper homeostatic functioning and information processing, but can also cause significant damage and cell death if dysregulated. During embryonic and early post-natal development, massive neurogenesis occurs, a process that continues at a limited rate in adulthood in two neurogenic niches, one in the lateral ventricle and the other in the hippocampal dentate gyrus. When metabolic demand does not correspond with supply, which can occur dramatically in the case of hypoxia or ischemia, or more subtly in the case of neuropsychiatric or neurodegenerative disorders, both of these neurogenic niches can respond—either in a beneficial manner, to regenerate damaged or lost tissue, or in a detrimental fashion—creating aberrant synaptic connections. In this review, we focus on the complex relationship that exists between the cerebral vasculature and neurogenesis across development and in disease states including hypoxic-ischemic injury, hypertension, diabetes mellitus, and Alzheimer’s disease. Although there is still much to be elucidated, we are beginning to appreciate how neurogenesis may help or harm the metabolically-injured brain, in the hopes that these insights can be used to tailor novel therapeutics to regenerate damaged tissue after injury.

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Section: The Anatomical Formation Of Hippocampal Vasculature Neuronsmentioning

confidence: 99%

The Hippocampal Neuro-Glio-Vascular Network: Metabolic Vulnerability and Potential Neurogenic Regeneration in Disease

Kirschen

Kery

2018

BPL

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“…We should note that in using the CAV method that we recently reported to target astrocytes, we found severe defects in hippocampusdependent memory following diphtheria toxin mediatedablation of astrocytes 8 . This provides us a novel noninvasive option to target astrocytes for behavior studies.…”

Section: Genetic Manipulationsmentioning

confidence: 99%

“…Recently, we reported that intravenously delivered Canine Adenovirus 2 (CAV2) preferentially targets perivascular astrocytes throughout the adult brain 8 . We can therefore deliver transgenes to astrocytes systemically, rather to only regions closely surrounding our injection site.…”

Section: Canine Adenoviral Astrocyte Targetingmentioning

confidence: 99%

“…Using viruses, we can control developmental stage and timing at which we express genes in astrocytes. This is potentially important because it allows us to dissect the contributions of astrocytes to time-sensitive processes such as neurogenesis or memory formation 8 . Also, viral manipulations may potentially allow for investigation of astrocyte activity in non-murine species, without having to overcome the technical difficulties of creating non-murine transgenic animals.…”

Section: Genetically Targeting Astrocytesmentioning

confidence: 99%

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Genetic targeting of astrocytes in the gliovascular unit of the adult brain

Wells¹

2018

J Cardiol and Cardiovasc Sciences

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The acute nature of neurological stroke disorders highlights the massive dependence of the brain on oxygen and energy supplies. The mechanisms of neural blood flow regulation have been intensely studied but are still unclear. Astrocytes are glial cells that communicate with both neurons and blood vessels, making them a cellular candidate for mediating neuronal blood flow. Evidence suggests that perivascular astrocytes of the brain do in part mediate blood flow corresponding to neuronal activity. However, the role of astrocytes in this respect is still to be defined and characterized. Fortunately, many recent technologies have emerged that allow us to investigate how astrocytes may accomplish this task. Gene expression strategies with rodent lines and viral transduction have allowed us to investigate astrocytes in a more targeted manner. Additionally, a variety of tools used previously to study neurons are now being applied to astrocytes. Studying how astrocytes may orchestrate brain blood flow is important for our ability to understand and treat neurovascular disease. We review current methods used to experimentally target, monitor, and manipulate astrocytes in the context of mediating neuronal blood flow.

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“…[1] ECs are vital bioactive and endocrine organs with critical functions in controlling vascular metabolism. [2] ECs situated between vascular tissues and blood can not only accomplish the metabolism of interstitial fluid and blood but also synthesize and secrete many vasoactive substances that maintain normal blood flow and long-term vessel patency as well as regulate blood pressure and anticoagulation-coagulation balance. [3]…”

Section: Introductionmentioning

confidence: 99%

Pivotal micro factors associated with endothelial cells

Meng

Zhang

Shan

et al. 2019

Chinese Medical Journal

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Objective: Recent studies have shown the important influence of various micro factors on the general biological activity and function of endothelial cells (ECs). Vascular endothelial growth factor ( VEGF ) and angiogenin ( ANG ) are classic micro factors that promote proliferation, differentiation, and migration of ECs. The underlying pathophysiological mechanisms and related pathways of these micro factors remain the focus of current research. Data sources: An extensive search was undertaken in the PubMed database by using keywords including “micro factors” and “endothelial cell.” This search covered relevant research articles published between January 1, 2007 and December 31, 2018. Study selection: Original articles, reviews, and other articles were searched and reviewed for content on micro factors of ECs. Results: VEGF and ANG have critical functions in the occurrence, development, and status of the physiological pathology of ECs. Other EC-associated micro factors include interleukin 10, tumor protein P53, nuclear factor kappa B subunit, interleukin 6, and tumor necrosis factor. The results of Gene Ontology analysis revealed that variations were mainly enriched in positive regulation of transcription by the RNA polymerase II promoter, cellular response to lipopolysaccharides, negative regulation of apoptotic processes, external side of the plasma membrane, cytoplasm, extracellular regions, cytokine activity, growth factor activity, and identical protein binding. The results of the Kyoto Encyclopedia of Genes and Genomes analysis revealed that micro factors were predominantly enriched in inflammatory diseases. Conclusions: In summary, the main mediators, factors, or genes associated with ECs include VEGF and ANG . The effect of micro factors on ECs is complex and multifaceted. This review summarizes the correlation between ECs and several micro factors.

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Genetic dissection of the neuro-glio-vascular machinery in the adult brain

Cited by 8 publications

References 65 publications

The Hippocampal Neuro-Glio-Vascular Network: Metabolic Vulnerability and Potential Neurogenic Regeneration in Disease

The Hippocampal Neuro-Glio-Vascular Network: Metabolic Vulnerability and Potential Neurogenic Regeneration in Disease

Genetic targeting of astrocytes in the gliovascular unit of the adult brain

Pivotal micro factors associated with endothelial cells

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