Mlc1-Expressing Perivascular Astrocytes Promote Blood–Brain Barrier Integrity DOI Creative Commons
John E. Morales, Arpan De, Alexandra A. Miller

и другие.

Journal of Neuroscience, Год журнала: 2021, Номер 42(8), С. 1406 - 1416

Опубликована: Дек. 29, 2021

In the mammalian brain, perivascular astrocytes (PAs) closely juxtapose blood vessels and are postulated to have important roles in control of vascular physiology, including regulation blood–brain barrier (BBB). Deciphering specific functions for PAs BBB biology, however, has been limited by ability distinguish these cells from other astrocyte populations. order characterize selective vivo , a new mouse model generated which endogenous megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) gene drives expression Cre fused mutated estrogen ligand-binding domain (Mlc1-T2A-CreERT2). This knock-in model, we term MLCT, allows identification tracking postnatal brain. We also demonstrate that MLCT-mediated ablation causes severe defects integrity, resulting premature death. PA loss results aberrant localization Claudin 5 -VE-Cadherin endothelial cell junctions as well robust microgliosis. Collectively, data reveal essential Mlc1-expressing regulating integrity mice indicate primary cause breakdown may contribute human neurologic disorders. SIGNIFICANCE STATEMENT Interlaced among billions neurons glia brain is an elaborate network vessels. Signals parenchyma unique permeability properties cerebral known However, understand very little about relative contributions different neural types functions. Here, show subpopulation leading junctions, breakdown, deficits.

Язык: Английский

Cellular and molecular mechanisms of the blood–brain barrier dysfunction in neurodegenerative diseases DOI Creative Commons

Tongli Chen,

Yan Dai,

Chenghao Hu

и другие.

Fluids and Barriers of the CNS, Год журнала: 2024, Номер 21(1)

Опубликована: Июль 19, 2024

Abstract Background Maintaining the structural and functional integrity of blood–brain barrier (BBB) is vital for neuronal equilibrium optimal brain function. Disruptions to BBB performance are implicated in pathology neurodegenerative diseases. Main body Early indicators multiple disorders humans animal models include impaired stability, regional cerebral blood flow shortfalls, vascular inflammation associated with dysfunction. Understanding cellular molecular mechanisms dysfunction crucial elucidating sustenance neural computations under pathological conditions developing treatments these This paper initially explores definition BBB, along signaling pathways regulating flow, inflammation. Subsequently, we review current insights into dynamics Alzheimer’s disease, Parkinson's amyotrophic lateral sclerosis, sclerosis. The concludes by proposing a unified mechanism whereby contributes disorders, highlights potential BBB-focused therapeutic strategies targets, outlines lessons learned future research directions. Conclusions breakdown significantly impacts development progression diseases, unraveling underlying elucidate how sustained devise approaches.

Язык: Английский

Процитировано

23
Foundations and implications of astrocyte heterogeneity during brain development and disease DOI
Alexandra L. Schober, Leigh E. Wicki‐Stordeur, Keith K. Murai

и другие.

Trends in Neurosciences, Год журнала: 2022, Номер 45(9), С. 692 - 703

Опубликована: Июль 23, 2022

Язык: Английский

Процитировано

41
Neuron-astrocyte omnidirectional signaling in neurological health and disease DOI Creative Commons
Dhruba Pathak, Krishnan Sriram

Frontiers in Molecular Neuroscience, Год журнала: 2023, Номер 16

Опубликована: Июнь 8, 2023

Astrocytes are an abundantly distributed population of glial cells in the central nervous system (CNS) that perform myriad functions normal and injured/diseased brain. exhibit heterogeneous phenotypes response to various insults, a process known as astrocyte reactivity. The accuracy precision brain signaling primarily based on interactions involving neurons, astrocytes, oligodendrocytes, microglia, pericytes, dendritic within CNS. have emerged critical entity because their unique role recycling neurotransmitters, actively modulating ionic environment, regulating cholesterol sphingolipid metabolism, influencing cellular crosstalk diverse neural injury conditions neurodegenerative disorders. However, little is about how synapse formation, axon specification, neuroplasticity, homeostasis, network activity following dynamic surveillance, CNS structure neurological diseases. Interestingly, tripartite hypothesis came light fill some knowledge gaps constitute interaction subpopulation synapses. This review highlights astrocytes' health neurological/neurodegenerative diseases arising from omnidirectional between astrocytes neurons at synapse. also recapitulates disruption with focus perturbations homeostatic astrocytic function key driver modulate molecular physiological processes toward

Язык: Английский

Процитировано

40
Astrocyte development in the cerebral cortex: Complexity of their origin, genesis, and maturation DOI Creative Commons
Solène Clavreul, Laura Dumas, Karine Loulier

и другие.

Frontiers in Neuroscience, Год журнала: 2022, Номер 16

Опубликована: Сен. 13, 2022

In the mammalian brain, astrocytes form a heterogeneous population at morphological, molecular, functional, intra-, and inter-region levels. past, few types of have been first described based on their morphology and, thereafter, according to limited key molecular markers. With advent bulk single-cell transcriptomics, diversity is now progressively deciphered its extent better appreciated. However, origin this remains unresolved, even though many recent studies unraveled specificities astroglial development both individual cell levels, particularly in cerebral cortex. Despite lack specific markers for each astrocyte subtype, understanding cellular events underlying cortical nevertheless within our reach thanks intersectional lineage tracing, microdissection, spatial mapping, transcriptomic tools. Here we present brief overview describing findings genesis maturation regulators during cortex development. All these considerably advanced knowledge astrogliogenesis, which relies more complex mode than neuronal counterparts, that undeniably impact

Язык: Английский

Процитировано

38
Emerging roles of astrocytes in blood-brain barrier disruption upon amyloid-beta insults in Alzheimer's disease DOI Creative Commons

MaggiePui Man Hoi,

Qian Yue

Neural Regeneration Research, Год журнала: 2023, Номер 0(0), С. 0 - 0

Опубликована: Янв. 1, 2023

Blood-brain barrier disruption occurs in the early stages of Alzheimer's disease. Recent studies indicate a link between blood-brain dysfunction and cognitive decline might accelerate disease progression. Astrocytes are most abundant glial cells central nervous system with important roles structural functional maintenance barrier. For example, astrocytic coverage around endothelial perivascular endfeet secretion homeostatic soluble factors two major underlying mechanisms physiological functions. Astrocyte activation is often observed patients, astrocytes expressing high level fibrillary acid protein detected amyloid-beta plaque elevated phagocytic ability for amyloid-beta. Structural alterations including swollen endfeet, somata shrinkage possess loss contribute to vascular integrity at capillary arterioles levels. In addition, skewed into proinflammatory oxidative profiles increased secretions vasoactive mediators inducing junction immune cell infiltration. this review, we summarize findings existing literature on relevance astrocyte alteration response amyloid pathology context dysfunction. First, briefly describe maintenance. Then, review clinical evidence patients preclinical animal cellular models. We further discuss changes that correlates astrocyte. Finally, evaluate secreted by astrocytes, providing potential molecular modulation. conclude perspective investigating therapeutic targeting protection

Язык: Английский

Процитировано

38
Astrocyte–Endotheliocyte Axis in the Regulation of the Blood–Brain Barrier DOI
Augustas Pivoriūnas, Alexei Verkhratsky

Neurochemical Research, Год журнала: 2021, Номер 46(10), С. 2538 - 2550

Опубликована: Май 7, 2021

Язык: Английский

Процитировано

49
Insulin regulates neurovascular coupling through astrocytes DOI Creative Commons
Ana M. Fernández,

Laura Martinez‐Rachadell,

Marta Navarrete

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2022, Номер 119(29)

Опубликована: Июль 14, 2022

Mice with insulin receptor (IR)–deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to and reduced brain glucose uptake, whereas IR-deficient disturbed mitochondrial glucose. While exploring the functional impact of function in astrocytes, we observed that GFAP-IR KO mice uncoupling blood flow uptake. Since higher levels reactive oxidant species (ROS), this leads stimulation hypoxia-inducible factor-1α and, consequently, vascular endothelial growth factor angiogenic pathway. Indeed, vascularity is normalized by treatment antioxidant N -acetylcysteine (NAC). NAC ameliorated high ROS levels, signaling neurovascular coupling mice. Our results indicate modulating uptake angiogenesis, receptors participate coupling.

Язык: Английский

Процитировано

28
Bridging metabolic syndrome and cognitive dysfunction: role of astrocytes DOI Creative Commons
Zihan Li, Yayi Jiang,

Caiyi Long

и другие.

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Май 10, 2024

Metabolic syndrome (MetS) and cognitive dysfunction pose significant challenges to global health the economy. Systemic inflammation, endocrine disruption, autoregulatory impairment drive neurodegeneration microcirculatory damage in MetS. Due their unique anatomy function, astrocytes sense integrate multiple metabolic signals, including peripheral hormones nutrients. Astrocytes synapses engage a complex dialogue of energetic immunological interactions. act as bridge between MetS dysfunction, undergoing diverse activation response dysfunction. This article summarizes alterations astrocyte phenotypic characteristics across pathological factors It also discusses clinical value critical pathologic diagnostic marker potential therapeutic target for MetS-associated

Язык: Английский

Процитировано

6
A Combination of Neurofilament Light, Glial Fibrillary Acidic Protein, and Neuronal Pentraxin-2 Discriminates Between Frontotemporal Dementia and Other Dementias DOI Creative Commons
Katharina Bolsewig, Yanaika S. Hok‐A‐Hin, Federica Nicoletta Sepe

и другие.

Journal of Alzheimer s Disease, Год журнала: 2022, Номер 90(1), С. 363 - 380

Опубликована: Сен. 16, 2022

Background: The differential diagnosis of frontotemporal dementia (FTD) is still a challenging task due to its symptomatic overlap with other neurological diseases and the lack biofluid-based biomarkers. Objective: To investigate diagnostic potential combination novel biomarkers in cerebrospinal fluid (CSF) blood. Methods: We included 135 patients from Center for Memory Disturbances, University Perugia, diagnoses FTD (n = 37), mild cognitive impairment Alzheimer’s disease (MCI-AD, n 47), Lewy body (PDD/DLB, 22), cognitively unimpaired as controls (OND, 29). Biomarker levels neuronal pentraxin-2 (NPTX2), pentraxin receptor, neurofilament light (NfL) glial fibrillary acidic protein (GFAP) were measured CSF, well NfL GFAP serum. assessed biomarker differences by analysis covariance generalized linear models (GLM). performed receiver operating characteristics analyses Spearman correlation determine associations. Results: CSF NPTX2 serum varied most between groups. NPTX2, differentiated groups good accuracy (FTD versus MCI-AD: area under curve (AUC) [95% CI] 0.89 [0.81–0.96]; PDD/DLB: AUC 0.82 [0.71–0.93]; OND: 0.80 [0.70–0.91]). correlated positively only PDD/DLB (ρ= 0.56, p < 0.05). did not correlate any Serum all 0.47–0.74, Conclusion: show combined NfL, differentiate neurodegenerative disorders.

Язык: Английский

Процитировано

24
Constructing Linear‐Oriented Pre‐Vascularized Human Spinal Cord Tissues for Spinal Cord Injury Repair DOI
Caixia Fan, Hui Cai, Lulu Zhang

и другие.

Advanced Healthcare Materials, Год журнала: 2024, Номер 13(18)

Опубликована: Март 27, 2024

Repairing spinal cord injury (SCI) is a global medical challenge lacking effective clinical treatment. Developing human-engineered tissues that can replenish lost cells and restore regenerative microenvironment offers promising potential for SCI therapy. However, creating vascularized human cord-like (VSCT) mimic the diverse cell types longitudinal parallel structural features of remains significant hurdle. In present study, VSCTs are engineered using embryonic cord-derived neural endothelial on linear-ordered collagen scaffolds (LOCS). Studies have shown astrocytes align along in VSCT, supporting axon extension from various neurons myelinated by oligodendrocytes. After transplantation into rats, VSCT survives at sites promotes endogenous regeneration vascularization, ultimately reducing scarring enhancing behavioral functional recovery. It suggests pre-vascularization beneficial treatment highlights important role exogenous tissue engineering.

Язык: Английский

Процитировано

5