Age-related changes in choroid plexus and blood–cerebrospinal fluid barrier function in the sheep

• Published in: Experimental gerontology Vol. 44; no. 4; pp. 289 - 296
• Main Authors: Chen, R.L., Kassem, N.A., Redzic, Z.B., Chen, C.P.C., Segal, M.B., Preston, J.E.
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.04.2009; Elsevier
• Subjects: Aging - cerebrospinal fluid; Aging - metabolism; Aging - physiology; Animals; Biological Transport - physiology; Biomarkers - cerebrospinal fluid; Biomarkers - metabolism; Blood-Brain Barrier - metabolism; Blood–brain barrier; Blood–cerebrospinal fluid barrier; Cerebrospinal fluid; Cerebrospinal fluid proteins; Cerebrospinal fluid secretion; Choroid plexus; Choroid Plexus - metabolism; Sheep; Sheep, Domestic; Sodium uptake; Choroid plexus; Blood–cerebrospinal fluid barrier; Sodium uptake; Cerebrospinal fluid; Cerebrospinal fluid secretion; Cerebrospinal fluid proteins; Blood–brain barrier; blood-brain barrier; blood-cerebrospinal fluid barrier; sodium uptake; cerebrospinal fluid; cerebrospinal fluid secretion; cerebrospinal fluid proteins
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2008.12.004

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 22Na + uptake and efflux by the CP. Steady-state extractions of a low and medium size molecular weight extracellular space marker, 14C-mannitol and 3H-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, 125I-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.