Cerebrospinal Fluid Proteomes: From Neural Development to Neurodegenerative Diseases

Abstract

Global characterisation of proteins and the comparison between proteomes is providing new insights into general biological structures and processes, as well as between physiological and pathological conditions. During both embryonic development and adult life, brain cavities and ventricles are filled with a complex protein-rich fluid, the cerebrospinal fluid (CSF). In the last few years, it has been suggested that adult CSF has a key function as a fluid pathway for delivering diffusible signals to the brain, thus affecting the behaviour of specific brain parenchyma cells, particularly the putative neural stem cells. Accordingly, some pathologies that affect the central nervous system (CNS), such as neurodegenerative diseases and/or neurological disorders, are reflected in CSF protein content, either as a cause or as a consequence. Adult CSF is considered to be the successor of embryonic CSF (E-CSF). Most of the proteins contained within E-CSF, as analysed in avians (chick) and mammals (rat and human), are also detected in adult humans, suggesting that some of their roles in CNS cell behaviour are similar. Despite the heterogeneity of the currently available data, which is due to technical differences in the proteomic analyses, the use of different model systems and the great variety of sample sources, it is increasingly clear that this fluid regulates the behaviour of neural stem cells throughout development and during adult life, thus suggesting a possible approach to brain cell therapies. This review focuses on current data regarding CSF proteomes in relation to CSF functions in both physiological and pathological conditions, as well as on CSF manufacture.

All-trans retinol and retinol-binding protein from embryonic cerebrospinal fluid exhibit dynamic behaviour during early central nervous system development

“…The analyses of the particular roles of some of these molecules has shown that one of the growth factors contained within E-CSF, fibroblast growth factor-2, is responsible for neuroepithelial cells proliferation and also at least partially for the neurogenic properties of this fluid [10]. Moreover, we have also recently demonstrated the involvement of lipoproteins contained within the E-CSF in anterior central nervous system (CNS) neurogenesis (unpublished data) [11].…”

Early embryonic brain development in rats requires the trophic influence of cerebrospinal fluid

“…Other examples of the influence of the CSF upon the behaviour of adult brain neural precursor cells have been established by Sawamoto et al, 2006, in which they demonstrated in adult mice that the oriented migration of neuronal precursor cells from the subventricular zone towards the rostral migratory stream depends on a gradient of chemorepulsive molecules in the CSF, created by the beating of cilia in lateral brain ventricles. Furthermore, changes in CSF composition have been related with certain neurodegenerative diseases, suggesting that the CSF is involved with normal and abnormal brain behaviour (Parada et al, 2007).…”

“…Our results help to demonstrate that CSF plays relevant roles in early brain development in different species of higher vertebrates. Today we have sufficient experimental evidence to support the idea that the CSF influences early brain development on the basis of its complex biological composition (Gato et al, 2004;Parada et al, 2005bParada et al, , 2006Parada et al, , 2007Gato and Desmond, 2009). The presence of osmotically active components in CSF such as proteoglycans and ions, appears to generate the expansive force involved in early brain growth and morphogenesis (Desmond and Jacobson, 1977;Gato et al, 1993;Alonso et al, 1998Alonso et al, , 1999Lowery and Sive, 2005).…”

Cerebrospinal fluid control of neurogenesis induced by retinoic acid during early brain development

“…We recently showed that, at the beginning of primary neurogenesis, both avian and mammal E-CSF proteomes include a set of molecules whose roles during development in systems other than E-CSF are related to crucial biological functions (Dziegielewska et al, 1981;Gato et al, 2004;Zapaterra et al, 2007; reviewed by Parada et al, 2007). A remarkable finding that may contribute to an understanding of E-CSF's overall effect on the neurogenesis of neuroepithelial precursors is the presence of retinol-binding protein (RBP) as well as all-trans retinol in both chick and rat E-CSF (Parada et al, 2005b(Parada et al, , 2008bParvas et al, 2008).…”