Comparative Studies of Polysialic Acids Derived from Five Different Vertebrate Brains

Abstract

Polysialic acid (polySia/PSA) is a linear homopolymer of sialic acid (Sia) that primarily modifies the neural cell adhesion molecule (NCAM) in mammalian brains. PolySia-NCAM not only displays an anti-adhesive function due to the hydration effect, but also possesses a molecule-retaining function via a direct binding to neurologically active molecules. The quality and quantity of polySia determine the function of polySia-NCAM and are considered to be profoundly related to the maintenance of normal brain functions. In this study, to compare the structures of polySia-NCAM in brains of five different vertebrates (mammals, birds, reptiles, amphibians, and fish), we adopted newly developed combinational methods for the analyses. The results revealed that the structural features of polySia considerably varied among different species. Interestingly, mice, as a mammal, possess eminently distinct types of polySia, in both quality and quantity, compared with those possessed by other animals. Thus, the mouse polySia is of larger quantities, of longer and more diverse chain lengths, and of a larger molecular size with higher negative charge, compared with polySia of other species. These properties might enable more advanced brain function. Additionally, it is suggested that the polySia/Sia ratio, which likely reflects the complexity of brain function, can be used as a new promising index to evaluate the intelligence of different vertebrate brains.

Polysialic Acid in the Immune System

“…It consists of periodate oxidation of Sia residues and fluorescent labeling with DMB detecting a2,8linked oligo/polySia structures using combinatorial platforms such as reverse-phase HPLC with fluorescence detection (RPLC-FD) (116,117,136,137). An additional approach that provides similar results and uses soft acid conditions is mild acid hydrolysisfluorometric anion-exchange chromatography method (MH-FAEC), recently adapted for oligo-PolySia analysis (138).…”

“…The semiquantitative or qualitative analysis represented by Western blot (WB) and quantitative analysis such as ELISA and flow cytometry are mostly based in immunodetection of polySia (138,139). A disadvantage of ELISA is that it cannot distinguish polySia of different chain lengths and WB only offers relative quantification of polySia based on differential densitometry associated with chemiluminescent and fluorescent signal obtained from blots.…”

The Function of Sialidase Revealed by Sialidase Activity Imaging Probe

“…Sialic acid is abundant in the brain and is involved in various functions such as axonal outgrowth, neurotransmission, memory, and activities of voltage-gated sodium channel, voltage-gated calcium channels, N -methyl-D-aspartate (NMDA) receptor, and amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor [ 1 , 2 , 3 ]. Polysialic acid (PSA) is a linear homopolymer of sialic acid and can be detected in a wide range of eukaryotes, including vertebrates and invertebrates, and prokaryotes as well [ 4 ]. In the mammalian brain, PSAs are involved in the neural cell adhesion molecule (NCAM)-mediated inhibition of synaptogenesis and capture of brain-derived neurotrophic factor (BDNF) and dopamine [ 5 , 6 ].…”