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Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach.

ABSTRACT: Exchange mechanisms across the blood-cerebrospinal fluid (CSF) barrier in the choroid plexuses within the cerebral ventricles control access of molecules to the central nervous system, especially in early development when the brain is poorly vascularised. However, little is known about their molecular or developmental characteristics. We examined the transcriptome of lateral ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous genes identified in the adult were expressed at similar levels at E15, indicating substantial plexus maturity early in development. Some genes coding for key functions (intercellular/tight junctions, influx/efflux transporters) changed expression during development and their expression patterns are discussed in the context of available physiological/permeability results in the developing brain. Three genes: Secreted protein acidic and rich in cysteine (Sparc), Glycophorin A (Gypa) and C (Gypc), were identified as those whose gene products are candidates to target plasma proteins to choroid plexus cells. These were investigated using quantitative- and single-cell-PCR on plexus epithelial cells that were albumin- or total plasma protein-immunopositive. Results showed a significant degree of concordance between plasma protein/albumin immunoreactivity and expression of the putative transporters. Immunohistochemistry identified SPARC and GYPA in choroid plexus epithelial cells in the embryo with a subcellular distribution that was consistent with transport of albumin from blood to cerebrospinal fluid. In adult plexus this pattern of immunostaining was absent. We propose a model of the cellular mechanism in which SPARC and GYPA, together with identified vesicle-associated membrane proteins (VAMPs) may act as receptors/transporters in developmentally regulated transfer of plasma proteins at the blood-CSF interface.

SUBMITTER: Liddelow SA

PROVIDER: S-EPMC3310074 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach.

Liddelow Shane A SA Temple Sally S Møllgård Kjeld K Gehwolf Renate R Wagner Andrea A Bauer Hannelore H Bauer Hans-Christian HC Phoenix Timothy N TN Dziegielewska Katarzyna M KM Saunders Norman R NR

PloS one 20120321 3

Exchange mechanisms across the blood-cerebrospinal fluid (CSF) barrier in the choroid plexuses within the cerebral ventricles control access of molecules to the central nervous system, especially in early development when the brain is poorly vascularised. However, little is known about their molecular or developmental characteristics. We examined the transcriptome of lateral ventricular choroid plexus in embryonic day 15 (E15) and adult mice. Numerous genes identified in the adult were expressed ...[more]

PMID: 22457777

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Project description:ObjectiveOur objective is to explore whether blood-cerebrospinal fluid (CSF) barrier biomarkers differ in episodic migraine (EM) or chronic migraine (CM) from controls.BackgroundReports of blood-brain barrier and blood-cerebrospinal fluid barrier (BCSFB) disruption in migraine vary. Our hypothesis is that investigation of biomarkers associated with blood, CSF, brain, cell adhesion, and inflammation will help elucidate migraine pathophysiology.MethodsWe recruited 14 control volunteers without headache disorders and 42 individuals with EM or CM as classified using the International Classification of Headache Disorders, 3rd edition, criteria in a cross-sectional study located at our Pasadena and Stanford headache research centers in California. Blood and lumbar CSF samples were collected once from those diagnosed with CM or those with EM during two states: during a typical migraine, before rescue therapy, with at least 6/10 level of pain (ictal); and when migraine free for at least 48 h (interictal). The average number of headaches per month over the previous year was estimated by those with EM; this enabled comparison of biomarker changes between controls and three headache frequency groups: <2 per month, 2-14 per month, and CM. Blood and CSF biomarkers were determined using antibody-based methods.ResultsAntimigraine medication was only taken by the EM and CM groups. Compared to controls, the migraine group had significantly higher mean CSF-blood quotients of albumin (Qalb : mean ± standard deviation (SD): 5.6 ± 2.3 vs. 4.1 ± 1.9) and fibrinogen (Qfib mean ± SD: 1615 ± 99.0 vs. 86.1 ± 55.0). Mean CSF but not plasma soluble vascular cell adhesion molecule-1 (sVCAM-1) levels were significantly higher in those with more frequent migraine: (4.5 ng/mL ± 1.1 in those with <2 headache days a month; 5.5 ± 1.9 with 2-14 days a month; and 7.1 ± 2.9 in CM), while the Qfib ratio was inversely related to headache frequency. We did not find any difference in individuals with EM or CM from controls for CSF cell count, total protein, matrix metalloproteinase-9, soluble platelet-derived growth factor receptor β, tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-6, IL-8, IL-10, or C-reactive protein.ConclusionsThe higher Qalb and Qfib ratios may indicate that the transport of these blood-derived proteins is disturbed at the BCSFB in persons with migraine. These changes most likely occur at the choroid plexus epithelium, as there are no signs of typical endothelial barrier disruption. The most striking finding in this hypothesis-generating study of migraine pathophysiology is that sVCAM-1 levels in CSF may be a biomarker of higher frequency of migraine and CM. An effect from migraine medications cannot be excluded, but there is no known mechanism to suggest they have a role in altering the CSF biomarkers.

Project description:The transportation is a crucial phase in beef cattle industry, and the annual losses caused by beef cattle transport stress are substantial. Several studies have described the effect of long distance transportation stress on animal health, such as disorder in nervous, endocrine, immune, and metabolic system. However, molecular mechanisms underlying short distance transportation stress is still poorly understood. Present study aims to investigate the effect of short distance transportation by measuring the hematological indices and transcriptomic analysis. In this study, a total 10 Qinchuan cattle were used to compare the molecular characteristics of blood before and after transportation. We have found that a stress-related marker "white blood cell count (WBC)" increased significantly after transportation. The decrease in triglyceride (TG), cholestenone (CHO), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) showed that energy expenditure was increased after transportation, but not enough to activate fatty decomposition. Intriguingly, the decrease of malondialdehyde (MDA) showed that cattle were more resilience to oxidative stress. The RNA-seq showed that 1,092 differentially expressed genes (DEGs) were found (329 up-regulated and 763 down-regulated) between group before and group after. The GO and KEGG enrichment showed that the metabolic pathway and B cell function related pathways were enriched. Furthermore, median absolute deviation (MAD) top 5,000 genes were used to construct a co-expression network by weighted correlation network analysis (WGCNA), and 11 independent modules were identified. Combing with protein-protein interaction (PPI) analysis, the verification of quantitative real-time PCR (qPCR) and the correlation of B cell function, structural maintenance of chromosomes 3 (SMC3), jun proto-oncogene (JUN), and C-X-C motif chemokine ligand 10 (CXCL10) were suggested as potential molecular markers in identification of short distance transportation. Collectively, the blood RNA-seq analysis and WGCNA indicated that the disorder of B cell differentiation, proliferation, survival, and apoptosis were the potential molecular mechanism in short distance transportation stress. In conclusion, our results provide the novel insight about potential biomarkers for short distance transportation stress, which may serve as for diagnosing and preventing this condition in beef industry.

Dataset Information

Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach.

Publications

Molecular characterisation of transport mechanisms at the developing mouse blood-CSF interface: a transcriptome approach.

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