Pericyte-derived Glial Cell Line-derived Neurotrophic Factor Increase the Expression of Claudin-5 in the Blood–brain Barrier and the Blood-nerve Barrier

Shimizu, Fumitaka; Sano, Yuichi; Saito, Kazuyuki; Abe, Masaaki; Maeda, Toshihiko; Haruki, Hiroyo; Kanda, Takashi

doi:10.1007/s11064-011-0626-8

Cited by 125 publications

(113 citation statements)

References 46 publications

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“…97 Shimizu et al demonstrated that the GDNF, secreted from the brain and peripheral nerve pericytes, is one of the key molecules responsible for the up-regulation of claudin-5 expression and the permeability in the BBB. 98 Furthermore, pericytes are able to internalize the amyloid-b peptides, which accumulate in brain of Alzheimer's disease patients. 97 With amyloid deposits detected within degenerating pericytes in the brains of patients with Alzheimer's disease, it seems that pericyte dysfunction may also play a role in cerebral hypoperfusion and impaired amyloid b-peptide clearance in Alzheimer's disease.…”

Section: Astrocytesmentioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

344

260

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The age-associated decline of the neurological and cognitive functions becomes more and more serious challenge for the developed countries with the increasing number of aged populations. The morphological and biochemical changes in the aging brain are the subjects of many extended research projects worldwide for a long time. However, the crucial role of the blood-brain barrier (BBB) impairment and disruption in the pathological processes in age-associated neurodegenerative disorders received special attention just for a few years. This article gives an overview on the major elements of the blood-brain barrier and its supporting mechanisms and also on their alterations during development, physiological aging process and age-associated neurodegenerative disorders (Alzheimer's disease, multiple sclerosis, Parkinson's disease, pharmacoresistant epilepsy). Besides the morphological alterations of the cellular elements (endothelial cells, astrocytes, pericytes, microglia, neuronal elements) of the BBB and neurovascular unit, the changes of the barrier at molecular level (tight junction proteins, adheres junction proteins, membrane transporters, basal lamina, extracellular matrix) are also summarized. The recognition of new players and initiators of the process of neurodegeneration at the level of the BBB may offer new avenues for novel therapeutic approaches for the treatment of numerous chronic neurodegenerative disorders currently without effective medication. KeywordsAging, blood-brain barrier, endothelial cells, neurodegenerative disorders, transport systems Structure of the blood-brain barrier (BBB)Homeostasis of the extracellular microenvironment in the neural tissue of the brain as well as its protection against neurotoxic compounds and variations in the composition of the blood are important for normal function of the neurons. It is warranted by a structure formed between blood and brain, which is therefore called the BBB.1 Clear evidence for the existence of this permeability barrier in the brain emerged in 1909 with the demonstration by Edwin Goldman (a South African-German) that a dye injected into the blood stream of a rat stained the whole body -except for the brain and spinal cord. The opposite was also true: injection of the dye into the cerebral ventricles stained the brain and spinal cord but not the rest of the body. 2,3 This occurs because most organs of the body are perfused by capillaries lined with endothelial cells (ECs) that have small pores (fenestrations) to allow for the rapid movement of small molecules into the organ interstitial fluid from the circulation. However, the capillary endothelium of the brain and spinal cord lack these pores because the ECs of brain capillary are connected to each other by continuous tight junctions (TJs), produced by the interaction of several transmembrane proteins that project into and seal the paracellular pathway.3-5 The interaction of these junctional proteins effectively blocks the free diffusion of

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Section: Astrocytesmentioning

confidence: 99%

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Erdő

Dénès

Lange

2016

J Cereb Blood Flow Metab

344

260

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“…Although it has been demonstrated that RET/GFR␣ signaling is dispensable for thymic T cell development (3), application of GDNF led to a decrease in TNF-␣ secretion in monocytes (59). Furthermore, GDNF directly influences the blood-brain barrier by upregulation of the tight junction protein claudin 5, which leads to barrier-stabilizing effects (50,63).…”

Section: Gdnf Directly Promotes Barrier Maturation and Proliferation mentioning

confidence: 99%

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

Meir

Flemming

Burkard

et al. 2016

American Journal of Physiology-Gastrointestinal and Liver Physi

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Regulation of the intestinal epithelial barrier is a differentiated process, which is profoundly deranged in inflammatory bowel diseases. Recent data provide evidence that the glial cell line-derived neurotrophic factor (GDNF) is critically involved in intestinal epithelial wound healing and barrier maturation and exerts antiapoptotic effects under certain conditions. Furthermore, not only the enteric nervous system, but also enterocytes synthesize GDNF in significant amounts, which points to a potential para- or autocrine signaling loop between enterocytes. Apart from direct effects of GDNF on enterocytes, an immunomodulatory role of this protein has been previously assumed because of a significant reduction of inflammation in a model of chronic inflammatory bowel disease after application of GDNF. In this review we summarize the current knowledge of GDNF on intestinal epithelial barrier regulation and discuss the novel role for GDNF as a regulator of intestinal barrier functions in health and disease.

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“…Pericytes are one of the key players in angiogenesis and blood-brain-barrier integrity (Armulik et al, 2010). They also contribute to local homeostasis, secrete growth factors (Shimizu et al, 2012) and inflammatory molecules (Kovac et al, 2011) and are multipotent cells (Dore-Duffy, 2008;Ozen et al, 2012;Ozen et al, 2014;Paul et al, 2012)). Importantly, cerebral pericytes express platelet-derived growth factor (PDGF) receptor β (PDGFRβ) (Winkler et al, 2010), and are recruited by PDGF-BB-secreting endothelial cells to stabilise newly formed blood vessels (Armulik et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

Padel

Özen

Boix

et al. 2016

Neurobiology of Disease

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Parkinson's disease (PD) is a neurodegenerative disease where the degeneration of the nigrostriatal pathway leads to specific motor deficits. There is an unmet medical need for regenerative treatments that stop or reverse disease progression. Several growth factors have been investigated in clinical trials to restore the dopaminergic nigrostriatal pathway damaged in PD. Platelet-derived growth factor-BB (PDGF-BB), a molecule that recruits pericytes to stabilize microvessels, was recently investigated in a phase-1 clinical trial, showing a dose-dependent increase in dopamine transporter binding in the putamen of PD patients. Interestingly, evidence is accumulating that PD is paralleled by microvascular changes, however, whether PDGF-BB modifies pericytes in PD is not known. Using a pericyte reporter mouse strain, we investigate the functional and restorative effect of PDGF-BB in a partial 6-hydroxydopamine medial forebrain bundle lesion mouse model of PD, and whether this restorative effect is accompanied by changes in pericyte features. We demonstrate that a 2-week treatment with PDGF-BB leads to behavioural recovery using several behavioural tests, and partially restores the nigrostriatal pathway. Interestingly, we find that pericytes are activated in the striatum of PD lesioned mice and that these changes are reversed by PDGF-BB treatment. The modulation of brain pericytes may contribute to the PDGF-BB-induced neurorestorative effects, PDGF-BB allowing for vascular stabilization in PD. Pericytes might be a new cell target of interest for future regenerative therapies.

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Pericyte-derived Glial Cell Line-derived Neurotrophic Factor Increase the Expression of Claudin-5 in the Blood–brain Barrier and the Blood-nerve Barrier

Cited by 125 publications

References 46 publications

Age-associated physiological and pathological changes at the blood–brain barrier: A review

Age-associated physiological and pathological changes at the blood–brain barrier: A review

The glial cell-line derived neurotrophic factor: a novel regulator of intestinal barrier function in health and disease

Platelet-derived growth factor-BB has neurorestorative effects and modulates the pericyte response in a partial 6-hydroxydopamine lesion mouse model of Parkinson's disease

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