Neurobiology of resilience in depression: immune and vascular insights from human and animal studies DOI Creative Commons
Katarzyna Dudek, Laurence Dion‐Albert, Fernanda Neutzling Kaufmann

et al.

European Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 53(1), P. 183 - 221

Published: Aug. 17, 2019

Major depressive disorder (MDD) is a chronic and recurrent psychiatric condition characterized by depressed mood, social isolation anhedonia. It will affect 20% of individuals with considerable economic impacts. Unfortunately, 30-50% are resistant to current antidepressant treatments. MDD twice as prevalent in women associated symptoms different. Depression's main environmental risk factor stress, report higher levels stress daily life. However, not every stressed individual becomes depressed, highlighting the need identify biological determinants vulnerability but also resilience. Based on reverse translational approach, rodent models depression were developed study mechanisms underlying susceptibility vs Indeed, subpopulation animals can display coping set alterations leading The aetiology multifactorial involves several physiological systems. Exacerbation endocrine immune responses from both innate adaptive systems observed mice exhibiting depression-like behaviours. Increasing attention has been given neurovascular health since prevalence cardiovascular diseases found patients inflammatory conditions depression, treatment resistance relapse. Here, we provide an overview endocrine, vascular changes vs. resilience rodents when available, humans. Lack efficacy suggests that neuron-centric treatments do address important causal factors better understanding stress-induced adaptations, including sex differences, could contribute develop novel therapeutic strategies personalized medicine approaches.

Language: Английский

A blood–brain barrier overview on structure, function, impairment, and biomarkers of integrity DOI Creative Commons

Hossam Kadry,

Behnam Noorani, Luca Cucullo

et al.

Fluids and Barriers of the CNS, Journal Year: 2020, Volume and Issue: 17(1)

Published: Nov. 18, 2020

Abstract The blood–brain barrier is playing a critical role in controlling the influx and efflux of biological substances essential for brain’s metabolic activity as well neuronal function. Thus, functional structural integrity BBB pivotal to maintain homeostasis brain microenvironment. different cells structures contributing developing this are summarized along with functions that plays at brain–blood interface. We also explained shear stress maintaining integrity. Furthermore, we elaborated on clinical aspects correlate between disruption neurological pathological conditions. Finally, discussed several biomarkers can help assess permeability in-vitro or in-vivo briefly explain their advantages disadvantages.

Language: Английский

Citations

1137
The blood-brain barrier: Physiology and strategies for drug delivery DOI
Rucha Pandit, Liyu Chen, Jürgen Götz

et al.

Advanced Drug Delivery Reviews, Journal Year: 2019, Volume and Issue: 165-166, P. 1 - 14

Published: Nov. 29, 2019

Language: Английский

Citations

455
Structure, Function, and Regulation of the Blood-Brain Barrier Tight Junction in Central Nervous System Disorders DOI Creative Commons
Jeffrey J. Lochhead, Junzhi Yang, Patrick T. Ronaldson

et al.

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: Aug. 6, 2020

The blood-brain barrier (BBB) allows the brain to selectively import nutrients and energy critical neuronal function while simultaneously excluding neurotoxic substances from peripheral circulation. In contrast highly permeable vasculature present in most organs that reside outside of central nervous system (CNS), BBB exhibits a high transendothelial electrical resistance along with low rate transcytosis greatly restricted paracellular permeability. property permeability is controlled by tight junction protein complexes seal route between apposing microvascular endothelial cells. Although are principal contributors physical properties, they not static nature. Rather, dynamic structures where expression and/or localization individual constituent proteins can be modified response pathophysiological stressors. These stressors induce modifications involve de novo synthesis new or discrete trafficking mechanisms. Such responsiveness junctions diseases indicates these for maintenance CNS homeostasis. fulfillment this vital role, also major obstacle therapeutic drug delivery brain. There an opportunity overcome substantial optimize neuropharmacology via acquisition detailed understanding structure, function, regulation. review, we discuss physiological characteristics how properties regulate therapeutics treatment neurological diseases. Specifically, will modulation regulation both context disease states setting pharmacotherapy. particular, highlight potentially manipulated at molecular level increase levels transport

Language: Английский

Citations

301
Molecular adaptations of the blood–brain barrier promote stress resilience vs. depression DOI Creative Commons
Katarzyna Dudek, Laurence Dion‐Albert, Manon Lebel

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2020, Volume and Issue: 117(6), P. 3326 - 3336

Published: Jan. 23, 2020

Significance Thirty to fifty percent of depressed individuals are unresponsive commonly prescribed antidepressant treatments, suggesting that biological mechanisms, such as stress-induced inflammation and blood vessel dysfunction, remain untreated. The blood–brain barrier is the ultimate frontier between brain harmful toxins or inflammatory signals circulating in blood. Depression vulnerability chronic social stress associated with loss this integrity; however, mechanisms involved poorly understood. Identification adaptations leading resilience under stressful conditions could help develop novel treatments. Here we combined behavioral, pharmacological, cell-specific gene profiling experiments mice epigenetic, molecular, anatomical analysis human samples unravel therapeutic potential protect promote resilience.

Language: Английский

Citations

265
Immune cell trafficking across the blood-brain barrier in the absence and presence of neuroinflammation DOI Creative Commons
Luca Marchetti, Britta Engelhardt

Vascular Biology, Journal Year: 2020, Volume and Issue: 2(1), P. H1 - H18

Published: March 20, 2020

To maintain the homeostatic environment required for proper function of CNS neurons endothelial cells microvessels tightly regulate movement ions and molecules between blood CNS. The unique properties these vascular are termed blood-brain barrier (BBB) extend to regulating immune cell trafficking into privileged during health disease. In general, extravasation circulating is a multi-step process regulated by sequential interaction adhesion signalling cells. Accounting microvessels, migration across BBB distinct characterized several adaptations. Here we describe mechanisms that surveillance neuroinflammation, with focus on current state-of-the-art in vitro vivo imaging observations.

Language: Английский

Citations

208
The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation DOI Creative Commons
Ashley L. Comer, Micaël Carrier, Marie‐Ève Tremblay

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 27, 2020

Schizophrenia is a disorder with heterogeneous etiology involving complex interplay between genetic and environmental risk factors. The immune system now known to play vital roles in nervous function pathology through regulating neuronal glial development, synaptic plasticity, behavior. In this regard, the positioned as common link seemingly diverse factors for schizophrenia. Synthesizing information about how immune-brain axis affected by multiple these might interact schizophrenia necessary better understand pathogenesis of disease. Such knowledge will aid development more translatable animal models that may lead effective therapeutic interventions. Here, we provide an overview modulate function. We also explore including exposure pollution, gut dysbiosis, maternal activation early-life stress, consequences are linked microglial dysfunction. propose morphological signaling deficits blood-brain barrier, observed some individuals schizophrenia, can act gateway peripheral central inflammation, thus affecting microglia their essential functions. Finally, describe response neuroinflammation impact on brain homeostasis, well pathophysiology.

Language: Английский

Citations

173
Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment DOI Creative Commons
Chris Greene, Ruairi Connolly,

Declan Brennan

et al.

Nature Neuroscience, Journal Year: 2024, Volume and Issue: 27(3), P. 421 - 432

Published: Feb. 22, 2024

Abstract Vascular disruption has been implicated in coronavirus disease 2019 (COVID-19) pathogenesis and may predispose to the neurological sequelae associated with long COVID, yet it is unclear how blood–brain barrier (BBB) function affected these conditions. Here we show that BBB evident during acute infection patients COVID cognitive impairment, commonly referred as brain fog. Using dynamic contrast-enhanced magnetic resonance imaging, COVID-associated Transcriptomic analysis of peripheral blood mononuclear cells revealed dysregulation coagulation system a dampened adaptive immune response individuals Accordingly, showed increased adhesion human endothelial vitro, while exposure serum from induced expression inflammatory markers. Together, our data suggest sustained systemic inflammation persistent localized dysfunction key feature

Language: Английский

Citations

168
Blood-brain barrier associated tight junction disruption is a hallmark feature of major psychiatric disorders DOI Creative Commons
Chris Greene, Nicole Hanley, Matthew Campbell

et al.

Translational Psychiatry, Journal Year: 2020, Volume and Issue: 10(1)

Published: Nov. 2, 2020

Major psychiatric disorders affect 25% of the population. While genetic and environmental risk factors have been identified, underlying pathophysiology conditions, such as schizophrenia, bipolar disorder major depression remains largely unknown. Here, we show that endothelial associated tight junction components are differentially regulated at blood-brain barrier (BBB) in distinct neuroanatomic regions human donor brain tissues. Previous studies shown associations between BBB disruption development behaviours rodents. Using immunohistochemistry qRT-PCR, expression claudin-5 is reduced hippocampus individuals diagnosed with or schizophrenia. We also levels mRNA transcripts, including claudin-5, claudin-12 ZO-1 correlate disease duration age onset a range disorders. Together, these data dysregulation common pathology observed across Targeting regulating protein integrity could, therefore, represent novel therapeutic strategy for conditions.

Language: Английский

Citations

146
Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia DOI Creative Commons
Nathalie Jurisch‐Yaksi, Emre Yaksi, Çağhan Kızıl

et al.

Glia, Journal Year: 2020, Volume and Issue: 68(12), P. 2451 - 2470

Published: May 31, 2020

The neuroscience community has witnessed a tremendous expansion of glia research. Glial cells are now on center stage with leading roles in the development, maturation, and physiology brain circuits. Over course evolution, have highly diversified include radial glia, astroglia or astrocytes, microglia, oligodendrocytes, ependymal cells, each having dedicated functions brain. zebrafish, small teleost fish, is no exception to this recent evidences point evolutionarily conserved for development its nervous system. Due size, transparency, genetic amenability, zebrafish become an increasingly prominent animal model It enabled study neural circuits from individual entire brains, precision unmatched other vertebrate models. Moreover, high neurogenic regenerative potential attracted lot attention research focusing stem neurodegenerative diseases. Hence, studies using provide fundamental insights about function, also elucidate molecular mechanisms neurological We will discuss here discoveries diverse neurogenesis, modulating neuronal activity regulating homeostasis at barriers. By comparing made various models, particularly mammals our goal highlight similarities differences biology among species, which could set new paradigms relevant humans.

Language: Английский

Citations

141
SGLT2 Inhibition via Empagliflozin Improves Endothelial Function and Reduces Mitochondrial Oxidative Stress: Insights From Frail Hypertensive and Diabetic Patients DOI Open Access
Pasquale Mone, Fahimeh Varzideh, Stanislovas S. Jankauskas

et al.

Hypertension, Journal Year: 2022, Volume and Issue: 79(8), P. 1633 - 1643

Published: July 13, 2022

Frailty is a multidimensional condition often diagnosed in older adults with hypertension and diabetes, both these conditions are associated endothelial dysfunction oxidative stress. We investigated the functional role of SGLT2 (sodium glucose cotransporter 2) inhibitor empagliflozin frail diabetic hypertensive adults.

Language: Английский

Citations

136