scholarly journals Brain barriers: Crosstalk between complex tight junctions and adherens junctions

2015 ◽  
Vol 209 (4) ◽  
pp. 493-506 ◽  
Author(s):  
Silvia Tietz ◽  
Britta Engelhardt
Keyword(s):  
Tight Junctions ◽  
Adherens Junctions ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Barrier Integrity ◽  
Promising Target ◽  
The Central Nervous System ◽  
Junctional Complexes ◽  
Paracellular Diffusion ◽  
Brain Barriers

Unique intercellular junctional complexes between the central nervous system (CNS) microvascular endothelial cells and the choroid plexus epithelial cells form the endothelial blood–brain barrier (BBB) and the epithelial blood–cerebrospinal fluid barrier (BCSFB), respectively. These barriers inhibit paracellular diffusion, thereby protecting the CNS from fluctuations in the blood. Studies of brain barrier integrity during development, normal physiology, and disease have focused on BBB and BCSFB tight junctions but not the corresponding endothelial and epithelial adherens junctions. The crosstalk between adherens junctions and tight junctions in maintaining barrier integrity is an understudied area that may represent a promising target for influencing brain barrier function.

Tight junctions contain oligomeric protein assembly critical for maintaining blood–brain barrier integrity in vivo

2007 ◽  
Vol 0 (0) ◽  
pp. 071106212736002-??? ◽  
Author(s):  
Gwen McCaffrey ◽  
William D. Staatz ◽  
Carolyn A. Quigley ◽  
Nicole Nametz ◽  
Melissa J. Seelbach ◽  
...  
Keyword(s):  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Protein Assembly ◽  
Brain Barrier ◽  
Barrier Integrity ◽  
Blood Brain ◽  
Oligomeric Protein ◽  
Blood Brain Barrier Integrity

Intercellular junctions in the central nervous system of insects

1977 ◽  
Vol 26 (1) ◽  
pp. 175-199
Author(s):  
N.J. Lane ◽  
H.L. Skaer ◽  
L.S. Swales
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Gap Junctions ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Intercellular Junctions ◽  
Brain Barrier ◽  
Insect Species ◽  
Blood Brain ◽  
The Central Nervous System

The intercellular junctional complexes in the central nervous system (CNS) from a variety of insect species have been examined by thin-sectioning and freeze-fracturing techniques. Of particular concern has been the fine-structural basis of the blood-brain barrier observed to be present in the outer perineurial layer around the avascular insect CNS. The basis of this has been found in the form of tight junctions (zonulae occludentes) present both in sections and in replicas of the perineurium. In the latter, they appear as one or two simple linear ridges, lying parallel to the outer surface, which occasionally display overlapping. The complex geometry of the interdigitating perineurial cells apparently permits such a relatively simple series of ridges to function as a barrier, since tracers are found not to penetrate beyond this level into the underlying nervous tissue. Such evidence is supported by microprobe X-ray analysis of lanthanum-incubated tissues, the perineurium compared with the glia-ensheathed axons showing the presence and absence of lanthanum, respectively. Possible physiological mechanisms that could operate ‘in vitro’ to maintain the blood-brain barrier are also considered. Other intercellular junctions such as desmosomes, septate junctions and gap junctions are found in the perineurial layer too, the last exhibiting EF particle plaques and PF pits. Glia-glia junctions also occur in some insect species; they include desmosomes, inverted gap junctions and occasional tight junctions. Septate, gap and tight junctions are also found on the membranes of tracheoles penetrating the CNS. Short, ridge-like elaborations and other particle arrays are found on the PF on the axon surfaces and the significance of these structures is discussed.

scholarly journals Size-selective loosening of the blood-brain barrier in claudin-5–deficient mice

2003 ◽  
Vol 161 (3) ◽  
pp. 653-660 ◽  
Author(s):  
Takehiro Nitta ◽  
Masaki Hata ◽  
Shimpei Gotoh ◽  
Yoshiteru Seo ◽  
Hiroyuki Sasaki ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Endothelial Cells ◽  
Nervous System ◽  
Blood Vessels ◽  
Tight Junctions ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
The Central Nervous System ◽  
Deficient Mice

Tight junctions are well-developed between adjacent endothelial cells of blood vessels in the central nervous system, and play a central role in establishing the blood-brain barrier (BBB). Claudin-5 is a major cell adhesion molecule of tight junctions in brain endothelial cells. To examine its possible involvement in the BBB, claudin-5–deficient mice were generated. In the brains of these mice, the development and morphology of blood vessels were not altered, showing no bleeding or edema. However, tracer experiments and magnetic resonance imaging revealed that in these mice, the BBB against small molecules (<800 D), but not larger molecules, was selectively affected. This unexpected finding (i.e., the size-selective loosening of the BBB) not only provides new insight into the basic molecular physiology of BBB but also opens a new way to deliver potential drugs across the BBB into the central nervous system.

scholarly journals Functional Expression of Choline Transporters in the Blood–Brain Barrier

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2265 ◽  
Author(s):  
Masato Inazu
Keyword(s):  
Central Nervous System ◽  
Blood Brain Barrier ◽  
Cholinergic Neurons ◽  
Brain Barrier ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Choline Transporter ◽  
Blood Brain ◽  
The Central Nervous System ◽  
The Brain

Cholinergic neurons in the central nervous system play a vital role in higher brain functions, such as learning and memory. Choline is essential for the synthesis of the neurotransmitter acetylcholine by cholinergic neurons. The synthesis and metabolism of acetylcholine are important mechanisms for regulating neuronal activity. Choline is a positively charged quaternary ammonium compound that requires transporters to pass through the plasma membrane. Currently, there are three groups of choline transporters with different characteristics, such as affinity for choline, tissue distribution, and sodium dependence. They include (I) polyspecific organic cation transporters (OCT1-3: SLC22A1-3) with a low affinity for choline, (II) high-affinity choline transporter 1 (CHT1: SLC5A7), and (III) choline transporter-like proteins (CTL1-5: SLC44A1-5). Brain microvascular endothelial cells, which comprise part of the blood–brain barrier, take up extracellular choline via intermediate-affinity choline transporter-like protein 1 (CTL1) and low-affinity CTL2 transporters. CTL2 is responsible for excreting a high concentration of choline taken up by the brain microvascular endothelial cells on the brain side of the blood–brain barrier. CTL2 is also highly expressed in mitochondria and may be involved in the oxidative pathway of choline metabolism. Therefore, CTL1- and CTL2-mediated choline transport to the brain through the blood–brain barrier plays an essential role in various functions of the central nervous system by acting as the rate-limiting step of cholinergic neuronal activity.

scholarly journals Claudin-12 is not required for blood–brain barrier tight junction function

2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Mariana Castro Dias ◽  
◽  
Caroline Coisne ◽  
Pascale Baden ◽  
Gaby Enzmann ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Cell Types ◽  
Brain Barrier ◽  
Blood Brain ◽  
Exact Function ◽  
Associated Proteins ◽  
Junctional Complexes ◽  
Paracellular Diffusion ◽  
Cardiovascular Functions

Abstract Background The blood–brain barrier (BBB) ensures central nervous system (CNS) homeostasis by strictly controlling the passage of molecules and solutes from the bloodstream into the CNS. Complex and continuous tight junctions (TJs) between brain endothelial cells block uncontrolled paracellular diffusion of molecules across the BBB, with claudin-5 being its dominant TJs protein. However, claudin-5 deficient mice still display ultrastructurally normal TJs, suggesting the contribution of other claudins or tight-junction associated proteins in establishing BBB junctional complexes. Expression of claudin-12 at the BBB has been reported, however the exact function and subcellular localization of this atypical claudin remains unknown. Methods We created claudin-12-lacZ-knock-in C57BL/6J mice to explore expression of claudin-12 and its role in establishing BBB TJs function during health and neuroinflammation. We furthermore performed a broad standardized phenotypic check-up of the mouse mutant. Results Making use of the lacZ reporter allele, we found claudin-12 to be broadly expressed in numerous organs. In the CNS, expression of claudin-12 was detected in many cell types with very low expression in brain endothelium. Claudin-12lacZ/lacZ C57BL/6J mice lacking claudin-12 expression displayed an intact BBB and did not show any signs of BBB dysfunction or aggravated neuroinflammation in an animal model for multiple sclerosis. Determining the precise localization of claudin-12 at the BBB was prohibited by the fact that available anti-claudin-12 antibodies showed comparable detection and staining patterns in tissues from wild-type and claudin-12lacZ/lacZ C57BL/6J mice. Conclusions Our present study thus shows that claudin-12 is not essential in establishing or maintaining BBB TJs integrity. Claudin-12 is rather expressed in cells that typically lack TJs suggesting that claudin-12 plays a role other than forming classical TJs. At the same time, in depth phenotypic screening of clinically relevant organ functions of claudin-12lacZ/lacZ C57BL/6J mice suggested the involvement of claudin-12 in some neurological but, more prominently, in cardiovascular functions.

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