The quantities of each major class of glycosaminoglycan were determined in rat cerebrum from postnatal day 5 to 30 months of age. Chondroitin sulphate, dermatan sulphate, heparan sulphate, heparin, and hyaluronate were found, but no keratan sulphate was detected. Large and rapid changes in glycosaminoglycan content were observed during the period of brain maturation, and thereafter relatively steady levels were maintained until after the age of 12 months. The most remarkable change in the aged rat cerebrum was the ratio by weight of hyaluronate to chondroitin sulphate, which was approximately 1:1 from postnatal day 10 to 18 months but increased to 2.6:1 by the age of 30 months. In immature rats, the proportion of nonsulphated and 6-sulphated disaccharides derived from chondroitinase AC digests of brain glycosaminoglycans was much greater than in adults. In mature rats, chondroitin sulphate was composed almost entirely of 4-sulphated disaccharide subunits. The possibility that these changes could affect the permeability properties of the cerebral extracellular space and ionic equilibria in the brain is discussed.
The inability of retinal pigment epithelium to phagocytose shed photoreceptor disks is a cause of retinal degeneration in the Royal College of Surgeons rat; retinal pigment epithelial phagocytosis and disk shedding are regulated by the diurnal rhythm of retinal melatonin level. The diurnal rhythms of the electroretinogram (particularly that of the retinal pigment epithelial potential, the electroretinographic c-wave) and retinal melatonin content were thus investigated in Royal College of Surgeons rats from postnatal day 17 to 24, the period preceding retinal degeneration. The amplitudes of both the b- and c-waves of the electroretinogram fell significantly during the peak time of rod disk shedding and rose after the time of expected light off in the control and dystrophic rats. While the b-wave rhythms did not differ between the two strains, diurnal changes in the c-wave were significantly less distinct in the dystrophic rats than in controls. This difference may reflect lack of phagocytosis in dystrophic rats. Furthermore, the ERG c-wave was significantly larger and prolonged, and the retinal melatonin content higher, in dystrophic rats of this age group than in controls. It appears that retinal melatonin metabolism may play an important role in the maintenance of retinal pigment epithelial and photoreceptor function.
Each of the known classes of mammalian glycosaminoglycans, with the exception of keratan sulphate, was found in cerebral cortex samples from patients with Alzheimer-type dementia and age-matched controls. These molecules were quantitated, after electrophoresis and staining with Alcian Blue dye, by scanning densitometry. No significant differences were found between the mean levels of each of the above glycosaminoglycans in frontal cortex from patients with dementia compared with controls. An increase (26%; p less than 0.05) in the mean level of hyaluronate, but not of other glycosaminoglycans, was found in temporal cortex samples. On the other hand, the uronic acid content of hyaluronate degradation products following Streptomyces hyaluronidase treatment of brain glycosaminoglycans did not reveal any statistically significant changes in Alzheimer's disease. HPLC of disaccharide products from Arthrobacter chondroitinase AC digests did not reveal any significant changes in sulphate substitution of chondroitin sulphate in Alzheimer brain.
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