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The inner CSF-brain barrier: developmentally controlled access to the brain via intercellular junctions.

Whish S, Dziegielewska KM, Møllgård K, Noor NM, Liddelow SA, Habgood MD, Richardson SJ, Saunders NR - Front Neurosci (2015)

Bottom Line: These intercellular connections do not provide a diffusional restrain between the two compartments.Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis.These results provide information about physiological, molecular and morphological-related permeability changes occurring at the inner cerebrospinal fluid-brain barrier during brain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, University of Melbourne Parkville, VIC, Australia.

ABSTRACT
In the adult the interface between the cerebrospinal fluid and the brain is lined by the ependymal cells, which are joined by gap junctions. These intercellular connections do not provide a diffusional restrain between the two compartments. However, during development this interface, initially consisting of neuroepithelial cells and later radial glial cells, is characterized by "strap" junctions, which limit the exchange of different sized molecules between cerebrospinal fluid and the brain parenchyma. Here we provide a systematic study of permeability properties of this inner cerebrospinal fluid-brain barrier during mouse development from embryonic day, E17 until adult. Results show that at fetal stages exchange across this barrier is restricted to the smallest molecules (286Da) and the diffusional restraint is progressively removed as the brain develops. By postnatal day P20, molecules the size of plasma proteins (70 kDa) diffuse freely. Transcriptomic analysis of junctional proteins present in the cerebrospinal fluid-brain interface showed expression of adherens junctional proteins, actins, cadherins and catenins changing in a development manner consistent with the observed changes in the permeability studies. Gap junction proteins were only identified in the adult as was claudin-11. Immunohistochemistry was used to localize at the cellular level some of the adherens junctional proteins of genes identified from transcriptomic analysis. N-cadherin, β - and α-catenin immunoreactivity was detected outlining the inner CSF-brain interface from E16; most of these markers were not present in the adult ependyma. Claudin-5 was present in the apical-most part of radial glial cells and in endothelial cells in embryos, but only in endothelial cells including plexus endothelial cells in adults. Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis. These results provide information about physiological, molecular and morphological-related permeability changes occurring at the inner cerebrospinal fluid-brain barrier during brain development.

No MeSH data available.


Related in: MedlinePlus

Total protein concentration in (A) and in CSF (B) during development in the mouse. Mean ± SEM (n = 3–4). *p < 0.05 compared with previous age group. E15 data from Liddelow et al. (2014). In CSF, maximum concentration was in the youngest embryos examined (E15). The lowest concentration was in adults. In plasma the lowest protein concentration was at E15 with a progressive increase to adulthood. ***p < 0.001. E, embryonic day; P, postnatal day.
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Figure 5: Total protein concentration in (A) and in CSF (B) during development in the mouse. Mean ± SEM (n = 3–4). *p < 0.05 compared with previous age group. E15 data from Liddelow et al. (2014). In CSF, maximum concentration was in the youngest embryos examined (E15). The lowest concentration was in adults. In plasma the lowest protein concentration was at E15 with a progressive increase to adulthood. ***p < 0.001. E, embryonic day; P, postnatal day.

Mentions: In order to establish if there is a correlation between changes in the permeability properties of the inner CSF–brain barrier and protein concentration in the CSF during brain development, total protein concentration in plasma and CSF of mice from E17 to adult was measured using the Bradford method (Bradford, 1976 see Materials and Methods). Results are shown in Figure 5. For completeness values obtained from a previous study (Liddelow et al., 2012) from E15 mice are also included.


The inner CSF-brain barrier: developmentally controlled access to the brain via intercellular junctions.

Whish S, Dziegielewska KM, Møllgård K, Noor NM, Liddelow SA, Habgood MD, Richardson SJ, Saunders NR - Front Neurosci (2015)

Total protein concentration in (A) and in CSF (B) during development in the mouse. Mean ± SEM (n = 3–4). *p < 0.05 compared with previous age group. E15 data from Liddelow et al. (2014). In CSF, maximum concentration was in the youngest embryos examined (E15). The lowest concentration was in adults. In plasma the lowest protein concentration was at E15 with a progressive increase to adulthood. ***p < 0.001. E, embryonic day; P, postnatal day.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4325900&req=5

Figure 5: Total protein concentration in (A) and in CSF (B) during development in the mouse. Mean ± SEM (n = 3–4). *p < 0.05 compared with previous age group. E15 data from Liddelow et al. (2014). In CSF, maximum concentration was in the youngest embryos examined (E15). The lowest concentration was in adults. In plasma the lowest protein concentration was at E15 with a progressive increase to adulthood. ***p < 0.001. E, embryonic day; P, postnatal day.
Mentions: In order to establish if there is a correlation between changes in the permeability properties of the inner CSF–brain barrier and protein concentration in the CSF during brain development, total protein concentration in plasma and CSF of mice from E17 to adult was measured using the Bradford method (Bradford, 1976 see Materials and Methods). Results are shown in Figure 5. For completeness values obtained from a previous study (Liddelow et al., 2012) from E15 mice are also included.

Bottom Line: These intercellular connections do not provide a diffusional restrain between the two compartments.Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis.These results provide information about physiological, molecular and morphological-related permeability changes occurring at the inner cerebrospinal fluid-brain barrier during brain development.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Therapeutics, University of Melbourne Parkville, VIC, Australia.

ABSTRACT
In the adult the interface between the cerebrospinal fluid and the brain is lined by the ependymal cells, which are joined by gap junctions. These intercellular connections do not provide a diffusional restrain between the two compartments. However, during development this interface, initially consisting of neuroepithelial cells and later radial glial cells, is characterized by "strap" junctions, which limit the exchange of different sized molecules between cerebrospinal fluid and the brain parenchyma. Here we provide a systematic study of permeability properties of this inner cerebrospinal fluid-brain barrier during mouse development from embryonic day, E17 until adult. Results show that at fetal stages exchange across this barrier is restricted to the smallest molecules (286Da) and the diffusional restraint is progressively removed as the brain develops. By postnatal day P20, molecules the size of plasma proteins (70 kDa) diffuse freely. Transcriptomic analysis of junctional proteins present in the cerebrospinal fluid-brain interface showed expression of adherens junctional proteins, actins, cadherins and catenins changing in a development manner consistent with the observed changes in the permeability studies. Gap junction proteins were only identified in the adult as was claudin-11. Immunohistochemistry was used to localize at the cellular level some of the adherens junctional proteins of genes identified from transcriptomic analysis. N-cadherin, β - and α-catenin immunoreactivity was detected outlining the inner CSF-brain interface from E16; most of these markers were not present in the adult ependyma. Claudin-5 was present in the apical-most part of radial glial cells and in endothelial cells in embryos, but only in endothelial cells including plexus endothelial cells in adults. Claudin-11 was only immunopositive in the adult, consistent with results obtained from transcriptomic analysis. These results provide information about physiological, molecular and morphological-related permeability changes occurring at the inner cerebrospinal fluid-brain barrier during brain development.

No MeSH data available.


Related in: MedlinePlus