Tight Junction in Blood‐Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances

Liu, Wei‐Ye; Wang, Zhibin; Zhang, Lichao; Wei, Xianzhu; Li, Ling

doi:10.1111/j.1755-5949.2012.00340.x

Cited by 235 publications

(160 citation statements)

References 106 publications

(135 reference statements)

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“…The TJP complex is composed of transmembranous occludin, claudins, and junctional adhesion molecules that connect to the actin cytoskeleton through intermediary TJP accessory/anchoring proteins ZO-1, -2, and -3 [14][15][16]. TJ complexes are highly dynamic structures that respond quickly to intracellular signaling events and may experience rapid changes in the subcellular distribution of their composite proteins, as well as fluctuations in gene expression and various post-translational modifications [15,17,18].…”

Section: Introductionmentioning

confidence: 99%

Identification and Dynamic Regulation of Tight Junction Protein Expression in Human Neural Stem Cells

Watters

Rom

Hill

et al. 2015

Stem Cells and Development

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Recent reports indicate that neural stem cells (NSCs) exist in a cluster-like formation in close proximity to cerebral microvessels. Similar appearing clusters can be seen ex vivo in NSC cultures termed neurospheres. It is known that this neurosphere configuration is important for preserving stemness and a proliferative state. How NSCs form neurospheres or neuroclusters remains largely undetermined. In this study, we show that primary human NSCs express the tight junction proteins (TJPs): zonula occludens-1 (ZO-1), occludin, claudin-1, -3, -5, and -12. The relative mRNA expression was measured by quantitative polymerase chain reaction, and protein expression was confirmed by flow cytometry and immunofluorescence microscopy. Our results show that downregulation of TJPs occurs as neuronal differentiation is induced, suggesting that control of TJPs may be tied to the neuronal differentiation program. Importantly, upon specific knockdown of the accessory TJP, ZO-1, undifferentiated NSCs showed decreased levels of key stem cell markers. Taken together, our results indicate that TJPs possibly aid in maintaining the intercellular configuration of NSCs and that reduction in TJP expression consequently affects the stemness status.

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Section: Introductionmentioning

confidence: 99%

Identification and Dynamic Regulation of Tight Junction Protein Expression in Human Neural Stem Cells

Watters

Rom

Hill

et al. 2015

Stem Cells and Development

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show abstract

“…This issue will not be discussed in this review except for when it is under hormonal control. The reader may find relevant information in some recent reviews [6,12]. 2.…”

Section: Transport Of Substances and Overcoming Of The Bbb -General Pmentioning

confidence: 99%

Hormones and the blood-brain barrier

Hampl

Bičı́ková

Sosvorova

2015

Hormone Molecular Biology and Clinical Investigation

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Hormones exert many actions in the brain, and brain cells are also hormonally active. To reach their targets in brain structures, hormones must overcome the blood-brain barrier (BBB). The BBB is a unique device selecting desired/undesired molecules to reach or leave the brain, and it is composed of endothelial cells forming the brain vasculature. These cells differ from other endothelial cells in their almost impermeable tight junctions and in possessing several membrane structures such as receptors, transporters, and metabolically active molecules, ensuring their selection function. The main ways how compounds pass through the BBB are briefly outlined in this review. The main part concerns the transport of major classes of hormones: steroids, including neurosteroids, thyroid hormones, insulin, and other peptide hormones regulating energy homeostasis, growth hormone, and also various cytokines. Peptide transporters mediating the saturable transport of individual classes of hormones are reviewed. The last paragraph provides examples of how hormones affect the permeability and function of the BBB either at the level of tight junctions or by various transporters.

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“…These proteins homotypically interact with extracellular domains of claudins and occludins from neighboring cells and with scaffold proteins like zonula occludens-1 and -2 with their intracellular domains. At the same time, these scaffold proteins interact with the actin cytoskeleton resulting in the tight union between adjacent endothelial cells in the BBB (Ebnet, 2008;Forster, 2008;Liu et al, 2012), which in conjunction maintain the brain homeostasis and proper function of the central nervous system under physiological conditions. Several endogenous molecules regulate the BBB properties, like the vascular endothelial growth factor (VEGF) or Wnt 7a and 7b among others.…”

Section: Introductionmentioning

confidence: 98%

Inhibition of prolactin with bromocriptine for 28days increases blood–brain barrier permeability in the rat

Rosas-Hernández¹,

Ramı́rez²,

Ramirez-Lee³

et al. 2015

Neuroscience

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Tight Junction in Blood‐Brain Barrier: An Overview of Structure, Regulation, and Regulator Substances

Cited by 235 publications

References 106 publications

Identification and Dynamic Regulation of Tight Junction Protein Expression in Human Neural Stem Cells

Identification and Dynamic Regulation of Tight Junction Protein Expression in Human Neural Stem Cells

Hormones and the blood-brain barrier

Inhibition of prolactin with bromocriptine for 28days increases blood–brain barrier permeability in the rat

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