Journal
EXPERIMENTAL GERONTOLOGY
Volume 44, Issue 4, Pages 289-296Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2008.12.004
Keywords
Choroid plexus; Cerebrospinal fluid; Cerebrospinal fluid secretion; Cerebrospinal fluid proteins; Blood-cerebrospinal fluid barrier; Blood-brain barrier; Sodium uptake
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Funding
- Biotechnology and Biological Sciences Research Council (BBSRC)
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Dysfunction of the choroid plexuses (CPs) and the blood-cerebrospinal fluid barrier (BCSFB) might contribute to age-related cognitive decline and neurodegenerative disease. We used the CPs from young (1-2 years), middle-aged (3-6 years) and old (7-10 years) sheep to explore effects of aging on various aspects of CP and BCSFB functions. Total protein in the cerebrospinal fluid (CSF) was significantly higher in old compared to young sheep and CSF secretion by the CP perfused in situ was significantly lower in both old and middle-aged when compared to young sheep, which correlated with reduced Na-22(+) uptake and efflux by the CP. Steady-state extractions of a low and medium size molecular weight extracellular space marker, 14 C-mannitol and 3 H-polyethylene glycol, respectively, were significantly higher in CPs from old compared to young animals; however, there was no significant difference in steady-state extraction of a high molecular weight marker, (125)l-bovine serum albumin. This indicates increased passive BCSFB permeability for small and medium sized molecules in old sheep. CP redox activity was significantly lower in the old animals as assessed by the MTT assay, however, there was no significant difference in ATP content and energy charge of the CP with age suggesting adequate baseline energy reserve capacity. These data indicate that normal aging processes alter protein content in the CSF, CSF secretion, integrity of the BCSFB and Na+ flux in the epithelial layer, which could impact on CSF homeostasis and turnover. (C) 2008 Elsevier Inc. All rights reserved.
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