A molecular characterization of the choroid plexus and stress-induced gene regulation.

The role of the choroid plexus (CP) in brain homeostasis is being increasingly recognized and recent studies suggest that the CP has a more important role in physiological and pathological brain functions than currently appreciated. To obtain additional insight on the CP function, we performed a proteomics and transcriptomics characterization employing a combination of high resolution tandem mass spectrometry and gene expression analyses in normal rodent brain. Using multiple protein fractionation approaches, we identified 1400 CP proteins in adult CP. Microarray-based comparison of CP gene expression with the kidney, cortex and hippocampus showed significant overlap between the CP and the kidney. CP gene profiles were validated by in situ hybridization analysis of several target genes including klotho, CLIC 6, OATP 14 and Ezrin. Immunohistochemical analyses were performed for CP and enpendyma detection of several target proteins including cytokeratin, Rab7, klotho, tissue inhibitor of metalloprotease 1 (TIMP1), MMP9 and glial fibrillary acidic protein (GFAP). The molecular functions associated with various proteins of the CP proteome indicate that it is a blood-cerebrospinal fluid (CSF) barrier that exhibits high levels of metabolic activity. We also analyzed the gene expression changes induced by stress, an exacerbating factor for many illnesses, particularly mood disorders. Chronic stress altered the expression of several genes, downregulating 5HT2C, glucocorticoid receptor and the cilia genes IFT88 and smoothened while upregulating 5HT2A, BDNF, TNFα and IL-1b. The data presented here attach additional significance to the emerging importance of CP function in brain health and CNS disease states.

Sidestream smoke inhalation decreases respiratory clearance of 99mTc-DTPA acutely.

BACKGROUND: The permeability of the alveolar-capillary barrier to an inhaled aerosol of technetium 99m labelled diethylenetriamine penta-acetate (99mTc-DTPA) is used as an index of alveolar epithelial injury. Permeability is greatly increased in active smokers. AIMS: To determine the effect of sidestream smoke inhalation on permeability as this has not been described previously. METHODS: We measured lung clearance of inhaled 99mTc-DTPA aerosol in 20 normal non-smoking subjects before and after exposure to one hour's sidestream smoke inhalation. RESULTS: Measured carbon monoxide (CO) levels rose to maximum of 23.5 +/- 6.2 ppm (mean +/- SD) from baseline values of 0.6 +/- 1.3 (p < 0.001) and plasma cotinine levels to a maximum of 9.5 +/- 4.5 nmol/L (mean +/- SD). The half time (T1/2 in minutes) for 99mTc-DTPA clearance rose from baseline 69.1 +/- 15.6 (mean +/- SD) to 77.4 +/- 17.8 (p < 0.05) after smoke exposure. No effect of 99mTc-DTPA scanning or of sidestream smoke was demonstrated on lung function. CONCLUSIONS: We conclude that low level sidestream smoke inhalation decreases 99mTc-DTPA clearance acutely in humans. The mechanism of this unexpected result is not established but may include differences in constituents between sidestream and mainstream smoke, alterations in pulmonary microvascular blood flow, or changes in surfactant due to an acute phase irritant response.