Elevation of CSF albumin in old sheep: relations to CSF turnover and albumin extraction at blood‐CSF barrier

Abstract

J. Neurochem. (2010) 113, 1230–1239. Abstract Albumin is the most abundant protein in both CSF and plasma, and albumin quotient is often used to assess the functions of brain barriers especially that of the blood‐CSF barrier [i.e. the choroid plexus (CP) which also secretes CSF]. In this study, we took albumin as a model molecule to investigate ageing‐related alterations in the CSF‐CP system in sheep. We found significant ageing‐related increases in the weight of lateral CP [122.4 ± 14.0 mg in the young, 198.6 ± 35.4 mg in the middle aged, 286.1 ± 25.1 mg in the old (p < 0.05)], in the CSF albumin as well as the albumin quotient. Albumin protein spots in old CSF displayed wider on 2D western immunoblotting images, and had higher densities on images of 2D large gels stained with Pro‐Q Emerald 488 compared to the young samples, suggesting ageing‐related post‐translational modification in the albumin. CSF secretion was reduced with age: 0.148 ± 0.013 mL/min/g in the young, 0.092 ± 0.02 mL/min/g in the middle aged, 0.070 ± 0.013 mL/min/g in the old (p < 0.05). The 125I‐BSA extraction was not different among the sheep groups, nor was altered by temperature reduction, monensin, nocodazole, anti‐transforming growth factor β receptor II antibody, as well as unlabelled albumins. In conclusion, elevation of albumin in old CSF is associated with reduced CSF secretion by the CP, which size increases with age. 125I‐BSA extract, reflecting the extracellular space rather than the active albumin uptake in the CP, is not different between ages. These early changes in health ageing may result in the accumulation and modifications of CSF proteins leading to neurotoxicity.

A novel method to study cerebrospinal fluid dynamics in rats

“…Abnormally low rates of CSF formation have been linked to the accumulation of neurotoxic substances, including amyloid-β, in aging and in Alzheimer's disease (Serot et al, 2011; Serot et al, 2012; Arbel-Ornath et al, 2013). Our data showing age-dependent rates of CSF formation accorded with previous work performed in rats studied using ventriculocisternal perfusion (Preston, 2001; Chiu et al, 2012), in sheep studied using an in situ perfused choroid plexus technique (Chen et al, 2009; Chen et al, 2010), and in humans studied using MRI (Bouzerar et al, 2013). The marked age-related changes in the rates of CSF formation observed by us and others point to important upstream mechanisms in CSF regulation that are only beginning to be explored (Johanson et al, 2008).…”

MRI Techniques and New Animal Models for Imaging the Brain

“…It has been demonstrated in sheep that the CSF content varies according to the cerebroventricular compartment (Fig. 6, GnRH, Caraty & Skinner 2008;MLT, Malpaux et al 2002, Tricoire et al 2003, light-dark cycles (Skinner & Malpaux 1999, Thiery et al 2006, Thiery et al 2009) and ageing (Chen et al 2010a, Chen et al 2010b). These findings suggest that the CSF is an active medium which could play a role in regulating various functions (Malpaux et al 2002, Skipor & Thiery 2008).…”

“…One of the hypotheses regarding the variations in CSF content linked to season or ageing concerns variations in the BBB permeability, as demonstrated in sheep (Chen et al 2010b, Lagaraine et al 2011. BBB involvement and dysfunction in brain disorders has been extensively documented (de Vries et al 1997, Forster 2008, Hawkins & Davis 2005, Strbian et al 2008.…”

Temporal course of cerebrospinal fluid dynamics and amyloid accumulation in the aging rat brain from three to thirty months

“…Recently, it was found that albumin (a soluble CSF protein) levels are elevated in elderly sheep associated with decreased CSF production and turnover [10]. Albumin accumulation in the CSF is typical of other soluble proteins in the CSF which, with aging, may increase as brain concentrations increase.…”