Age-related changes in central nervous system hyaluronic acid and chondroitin sulfate in senescence-accelerated mice

Age-related changes in cerebral hyaluronic acid (HA) and chondroitin sulfate (CS) in senescence-accelerated mice (SAM-P/8 parallel Odu, P substrain) were investigated. SAM-R/1 parallel Odu (R substrain) mice were used as controls. Levels of both HA and CS extracted from the defatted dry cerebrums at 7, 17, 27 and 37 weeks of age were determined by HPLC analysis after conversion to unsaturated disaccharides following enzymatic digestion. Glycosaminoglycan content (determined as uronic acid) was lower in P substrain mice than in the age-matched controls at all ages tested. Though the ratio of HA to CS was increased at 17 and 27 weeks in control mice, this ratio for the P substrain was already high at the initial test at 7 weeks and remained so thereafter. The CS chain consisted mainly of delta Di-4S, with delta Di-0S and delta Di-6S present only as minor components at all ages in both substrains. The HA chain consisted only of delta Di-HA for all ages in both substrains. The relative amount of each unsaturated disaccharide was higher in the R substrain than in the P substrain mice at all ages. We found that qualitative and quantitative changes in cerebral CS and HA were expressed relatively early in the P substrain mice compared to controls. We propose that these changes are associated with and may cause physiological and functional alterations associated with senescence in the CNS.