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Biomedical subjects

S Y Felten

Publications and source records attributed to S Y Felten.

80 records · Page 5Linked to original sources

The effect of diabetes on leucine and fucose incorporation into PNS myelin proteins.

Peripheral neuropathy is a common complication associated with diabetes mellitus. Segmental demyelination and other pathological changes frequently accompany loss of sensory amd motor nerve function. Morphological changes seen in diabetic nerve myelin may be a result of altered Schwann cell metabolism under hyperglycemic conditions. Using both alloxan and streptozotocin - induced diabetic rats of 2, 4 and 8 months duration of diabetes, metabolic changes in isolated sciatic nerve myelin were assessed using a double-label in vitro incubation system. Incorporation of 3H-fucose and 1-14C-leucine into myelin was determined per microgram protein. Specific activities of incorporated protein precursors were compared as a ratio of fucose to leucine. Using the Newman-Kuels test for multiple comparisons, statistically significant increases were found in the incorporation ratios of diabetic rats at 2 and 4 months of diabetes when tested against age-matched controls.

Animals↗

Sympathetic noradrenergic innervation of guinea-pig liver: histofluorescence and pharmacological studies.

Norepinephrine concentration was higher in guinea-pig liver than in rat or mouse liver and evidence was obtained that the norepinephrine was present within nerves. In guinea pigs, norepinephrine in liver was depleted by reserpine, 6-hydroxydopamine and metaraminol. The depletion by 6-hydroxydopamine and metaraminol was antagonized by prior treatment with desipramine, an inhibitor of uptake into norepinephrine neurons. Guinea-pig liver concentrated metaraminol to a greater extent than did rat liver; the concentration of metaraminol was lowered by desipramine pretreatment and, within three tissues of the guinea pig (heart greater than liver greater than muscle), paralleled the concentration of endogenous norepinephrine. These findings constitute pharmacological evidence for noradrenergic innervation of guinea-pig liver to a greater extent than in other species. Histofluorescence studies confirmed the existence of norepinephrine-containing nerve terminals in guinea-pig liver. Norepinephrine-containing varicosities were seen adjacent to the hepatic artery, portal vein and bile duct in the portal spaces and adjacent to sinusoid capillaries and hepatocytes in the liver parenchyma. These findings strengthen the evidence for sympathetic innervation of liver and suggest the guinea pig as a useful species in exploring physiological roles of noradrenergic innervation of liver.

Animals↗

Sympathetic innervation of the amphibian spleen: developmental studies in Xenopus laevis.

Spleens from larval and adult South African clawed frogs (Xenopus laevis) were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence for norepinephrine. Innervation of the larval Xenopus spleen is barely detectable at stage 54 and gradually increases during prometamorphosis (stage 57/58) until metamorphic climax (stage 66). This development of innervation late in the larval life of the animal was highly sensitive to environmental conditions and to rapidity at which development occurred. Prevention of overt metamorphosis by sodium perchlorate blockade prevented the development of noradrenergic (NA) splenic innervation in some, but not all, tadpoles examined. Depletion of T-lymphocytes by early larval thymectomy did not alter the kinetics or pattern of splenic NA innervation.

Animals↗

Substance P innervation of the rat thymus.

Immunohistochemistry for substance P (SP) in the rat thymus revealed fine varicose neural profiles in specific regions of the thymus. Thymic SP innervation was abundant within the capsule and interlobular septa. The majority of SP+ nerve fibers within the septa were free of vascular association, although some fibers were associated with the vasculature deep within the septa. SP+ nerve fibers entered the thymic cortex from the septa and distributed among cortical thymocytes and mast cells. Along the corticomedullary junction, SP+ nerve fibers were found in association with the vasculature. The medullary region of the thymus received only a sparse innervation of SP+ fibers. In addition, SP+ nerve fibers coursed adjacent to OX-8+ cells and mast cells in the extrathymic connective tissue surrounding the thymus. The present study provides evidence that SP is present in nerve fibers in the thymus, and may be available to interact with thymocytes, mast cells, and other cells in the thymus, and affect their development and function.

Animals↗

Decreased sympathetic innervation of spleen in aged Fischer 344 rats.

Splenic noradrenergic innervation in young adult and aged Fischer 344 rats was examined using fluorescence histochemistry for catecholamines and high performance liquid chromatography with electrochemical detection (LCEC) for the quantitation of norepinephrine (NE). In young adult rats, abundant noradrenergic plexuses followed the vasculature and trabeculae into splenic white pulp. In aged rats, noradrenergic innervation was reduced in density and in overall intensity of fluorescence, and splenic NE levels were significantly lower. The relationship between diminished noradrenergic innervation and diminished immune responsiveness in aging mammals, while not clear on a causal level, is presented as a hypothesis for further testing.

Aging↗

Chronic dietary pergolide preserves nigrostriatal neuronal integrity in aged-Fischer-344 rats.

Pergolide, a potent D2 presynaptic agonist with postsynaptic D2 agonist activity and some D1 agonist activity was administered in the diet (0.5 mg/kg/day) of male Fischer 344 rats from age 3 to age 26 months. We hypothesized that the potent D2 presynaptic activity would reduce the baseline release of dopamine (DA) and thereby slow the formation of toxic oxidative metabolites that lead to age-related deterioration of nigrostriatal DA neurons. Pair-fed rats served as controls. We observed age-related losses of fluorescent DA cell bodies in the substantia nigra pars compacta and of fluorescent DA terminals in the striatum; chronic pergolide administration prevented these losses. Pergolide administration also prevented the age-related diminution of DA fluorescence intensity in substantia nigra cell bodies. A large decline in 3H-DA uptake with age was partially prevented by pergolide administration. We found no age-related alteration in the concentration of DA in the striatum and pergolide did not alter this concentration. Pergolide treatment resulted in only minor alterations in striatal 3H-spiperone binding and no change in dendritic arborizations of either DA substantia nigra neurons or medium spiny striatal neurons. Pergolide administration also prevented an age-related decline in circulating FSH levels. The uptake data and quantitative morphological findings suggest that pergolide administration in the diet for 2 years exerts a protective effect on age-related deterioration of DA nigrostriatal neurons. This finding was consistent with clinical reports of a subset of patients with Parkinson's disease in whom long-term efficacy of pergolide therapy is observed.

Aging↗

Noradrenergic and peptidergic innervation of the amphibian spleen: comparative studies.

Spleens from representatives of the three amphibian orders were examined using sucrose-potassium phosphate-glyoxylic acid (SPG) histofluorescence to detect catecholamines and immunocytochemistry to detect several neural antigens. Nerve fibers are scattered throughout the spleens of adult salamanders (Taricha torosa, Notophthalmus viridescens, and Ambystoma mexicanum). A less abundant but similarly diffuse pattern of innervation characterizes the spleen of the caecilian, Typhlonectes sp. The spleen of the adult frog, Xenopus laevis, is separated into clearly defined compartments of red pulp and white pulp, much as is seen in the mammalian spleen. As in mammals, sympathetic innervation of the Xenopus spleen is noradrenergic (NA) and confined to the white pulp. The white pulp of Xenopus spleen also contains fibers which stain for neuropeptide Y and substance P. The spleen of the anuran, Rana pipiens, is also highly compartmentalized, with tyrosine hydroxylase positive fibers in proximity to blood vessels. These findings provide an anatomical substrate for neural-immune interactions in the Amphibia.

Amphibians↗

Age-associated alterations in sympathetic neural interactions with the immune system.

We have examined age-related alterations in sympathetic noradrenergic (NA) innervation in primary and secondary lymphoid organs from mouse and rat. As the thymus involuted with age, the density of NA innervation and norepinephrine (NE) concentration increased markedly. Total thymic NE was not altered significantly with age, suggesting that NA innervation is maintained as the thymus involutes. In the rat spleen, NA innervation and NE concentration were diminished with age. Enhanced antibody responses and in vitro proliferation to a T-dependent protein antigen were observed following selective destruction of NA nerve fibers with the neurotoxin 6-hydroxydopamine (6-OHDA), demonstrating that the diminished NA innervation in the aged spleen is capable of signaling the immune system. Plasticity of NA nerves in old rats was demonstrated following lesioning with 6-OHDA and in intact rats treated with L-deprenyl, a monoamine oxidase B inhibitor. These age-related alterations in NA innervation of lymphoid organs occur concurrently with age-associated changes in immune function. Understanding the functional relationship between these two physiological systems in aging will contribute to a greater understanding of sympathetic nervous system regulation of immune function.

Age Factors↗