摘要:

Abstract:Peripheral nerve demyelination was induced in cats by oral administration of ether extracts of Tullidora (Karwinskia humboldtiana). Proteins from several hindlimb nerves, spinal roots, and dorsal columns of the spinal cord were subjected to slab gel electrophoresis and quantified by densitometry. In Tullidora‐treated cats with severe motor disturbances, specific myelin proteins were reduced by at least 50% in motor nerves and less than 25% in cutaneous axons. There was a greater decrease of these proteins in the distal than in the cephalad segments of the sciatic nerve; no changes were detected either in the spinal roots or in the white matter of the spinal cord. Electron microscopy revealed intense demyelination in the motor nerves only. Both the density of the 100 Å‐thick neurofilaments and the relative proportion of a polypeptide with a molecular weight of 68,000 were considerably increased in the affected nerves. It is tentatively concluded that the active principles of Tullidora may enter the axons through the motor nerve terminals. The distal segments of the motor nerves would then be preferentially affected and demyelination could result from axonal da

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02370.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:One sciatic nerve of a White Leghorn hen was severed and the distal portion was allowed to undergo Wallerian degeneration. The change in histamine and DNA concentration and mast cell number was measured at different times following nerve sectioning in the proximal regenerating, distal degenerating, and intact, contralateral nerves. The experimental results revealed a significant accumulation of histamine in the proximal desheathed segment and in the contralateral “functional nerve,” whereas the biogenic amine in the distal desheathed nerve significantly decreased. The pattern of change of histamine in the distal and proximal nerve sheaths was different: it dropped at 2 h and then rose in the later stages of Wallerian degeneration. In the distal desheathed nerves and in both the proximal and distal nerve sheaths DNA increased significantly by 14 days. The number of mast cells appeared to be highest in the 14‐day distal nerve and in the 7‐day proximal nerve sheaths. These results support a dual localization of histamine in the peripheral nerve, and are consistent with the interpretation that the amine has either some role in neurotransmission or in the process of growth and regen

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02371.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The occurrence, metabolism, uptake, and release of noradrenaline were studied in the bovine retina with the following results. (1) Small amounts of noradrenaline occur in the retina and are restricted to the area corresponding to the inner nuclear and plexiform layers. (2) Retinal tissue can metabolise [14C]dopamine to form quantities of [14C]noradrenaline. (3) [14C]Noradrenaline can also be partly metabolised to form [14C]normetanephrine. (4) When bovine retinas were incubated with 5 × 10‐7M‐[3H]noradrenaline for 20 min and processed for autoradiography, most of the label was associated with apparent nerve processes in the inner plexiform layer. Biochemical analysis showed that more than 95% of the label was noradrenaline. (5) [14C]Noradrenaline uptake saturated with increasing noradrenaline concentrations and followed Michaelis‐Menten kinetics. This uptake could be accounted for by two processes, a high‐affinity system with aKm1of 5 × 10‐8M and aVmax1of 0.193 pmol/mg/10 min and a low‐affinity system with aKm2of 6.3 × 10‐5M and aVmax2of 0.109 nmol/mg/10 min. (6) Noradrenaline uptake was strongly dependent on temperature and sodium, less dependent on potassium, and independent of calcium and magnesium ions. (7) Centrally acting drugs, such as desipramine, imipramine, desmethylimipramine, and amitriptyline, inhibited noradrenaline uptake by more than 55% at the concentration of 5 × 10‐5M. These drugs at the same concentration diminished dopamine uptake by less than 30%. (8) Noradrenaline uptake is stereospecific, the (‐) isomer having a greater affinity for the uptake sites than the (+) isomer. (9) [14C]Noradrenaline in the retina could be released by increasing the external potassium concentration. This release was calcium‐dependent and was blocked by 20 mM‐cobalt chloride. The present studies could be interpreted as supporting the idea that noradrenaline acts as a

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02372.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The effect of mild hypoxic hypoxia on brain metabolism and acetylcholine synthesis was studied in awake, restrained rats. Since many studies of hypoxia are done with animals anesthetized with nitrous oxide (N2O), the effects of N2O were evaluated. N2O (70%) increased the cerebral cortical blood flow by 33% and the cortical metabolic rate of oxygen by 26%. In addition, the synthesis of acetylcholine in N2O‐anesthetized animals, measured with [U‐14C]glucose and [1‐2H2,2‐2H2]choline, decreased by 45 and 53%, respectively. Consequently, mild hypoxia was studied in unanesthetized rats. Control rats breathing 30% O2(partial pressure of oxygen, Pao2= 120 mm Hg) were compared with rats exposed to 15% O2(Pao2= 57 mm Hg) or 10% O2(Pao2= 42 mm Hg). The synthesis of acetylcholine, measured with [U‐14C]glucose, was decreased by 35 and 54% with 15% O2and 10% O2respectively; acetylcholine synthesis, measured with [1‐2H2,2‐2H2]choline, was decreased by 50 and 68% with 15% O2and 10% O2respectively. Animals breathing either 15% or 10% O2had normal cerebral metabolic rates of oxygen but had increased brain lactates and increased cortical blood flows compared with animals breathing 30% O2. These results show that even mild hypoxic hypoxia impairs acetylcholine synthesis, which in turn may account for the early symptoms of brain dysfunction associated

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02373.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The amino acid content of three tissues was measured in 10‐day‐old rats made hyperphenylalaninemic from age 3 to 10 days by daily injections of phenylalanine plus α‐methylphenylalanine to inhibit phenylalanine hydroxylase (PAH). At 12 h after the last injection, the concentrations of alanine, valine, methionine, isoleucine, and leucine in the cerebral hemispheres were depressed by 25–50%, whereas that of glycine was elevated 2.3‐fold. In the spinal cord, the levels of phosphoserine, methionine, and leucine were decreased by 40–50%, and those of serine and threonine increased by 50%. Tyrosine and phenylalanine concentrations were high in all tissues, 2–3 and 15–30 times normal, respectively; of the amino acids investigated, they were the only ones changed in the liver. Cerebral hyperglycinemia was also produced by chronic treatment with phenylalanine plusp‐chlorophenylalanine to inhibit PAH, but not by acute (12 h) hyperphenylalaninemia. An increase in cerebral phosphoserine phosphatase activity was greater in rats treated with phenylalanine plus PAH inhibitor than with inhibitor alone. The content of brain glycine normally declines with age from birth to 15 days; this decrease was prevented by chronic hyperphenylalaninemia. Attempts to reduce the cerebral glycine content of the hyperphenylalaninemic rats were unsuccessful. However, one of the therapeutic protocols, methionine loading, may be useful because it increased the methionine and decreased the phenylalanine con

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02374.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Myelinogenesis in developing rats was studied following chronic dosing with triethyl tin (TET), at a level of 1.0 mg TET/kg body wt/day. Experiments included starved controls with body weights depressed by 17 to 40% to equal those of the TET‐treated groups. Rats at ages of 16, 21, and 30 days showed decreases relative to well‐nourished controls in body weight, forebrain weight, myelin yield, cerebroside level, and specific activity of brain 2′,3′‐cyclic nucleotide‐3′‐phosphohydrolase when dosed with TET. At 30 days, myelin and cerebroside yields were reduced by approximately 55%, while CNP activity was reduced by less than 20%. No differences in the forebrain myelin protein composition between control, starved, and TET animals were noted. The rate of myelin protein synthesis relative to brain total protein (assayed by incorporation of intracranially injected [3H]glycine into brain homogenate and myelin proteins) was decreased in the TET rats in proportion to the decreased yield of myelin, but no particular myelin protein was preferentially affected. Matching starved controls exhibited similar body weight decreases, less pronounced forebrain weight decreases, and little or no decrease in myelin concentration. There was a relative increase in the myelin protein synthesis rate in the starved rats, indicating preferential utilization of limited protein precursors for myelin protein synthesis. Spinal cord myelin was also decreased in the TET rats, but less severely than in the forebrain. At all ages optic, but not sciatic, nerves showed decreases in myelin concentration with TET treatment. We conclude that TET inhibits forebrain growth and CNS myelination more severely than can be accounted for by a general m

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02375.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:The alkaline phosphatases (EC 3.1.3.1) are determined by at least three gene loci, which can be sharply distinguished one from another by their sensitivity to inhibition with various amino acids and peptides and by ther‐mostability. Alkaline phosphatase is present in the brains of guinea pig, rat, mouse, hamster, squirrel, rabbit, cat, sheep, cow, tamarin, baboon, and man. The gene locus coding for alkaline phosphatase in all these brains is the liver/ bone/kidney locus, as indicated by thermostability studies and by inhibition studies with L‐phenylalanine, L‐homoarginine, and L‐phenylalanylglycylglycine. The average brain alkaline phosphatase activity is about 35% of the average for the livers and only 7.2% and 4.4% of the average kidney and placental activities, respectively. During growth and development, brain alkaline phosphatase activity decreases in the mammals studied. The amount of change is tissue‐ and species

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02376.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Rapid cleavage of bovine and guinea pig myelin basic proteins by pepsin at pH 6.0 is limited to the Phe‐Phe bond in the middle of the molecule. In the rabbit protein, however, rapid cleavages occur elsewhere in addition to the Phe87‐Phe88bond in regions in which there are amino acid substitutions. Rapid cleavage occurs at the Leu151‐Phe152bond, at which Ile‐151 has been replaced by Leu, the residue that actually contributes the scissile bond. Rapid cleavages occur at the Phe44‐Phe45and Leu109‐Ser110bonds, which in the bovine and guinea pig proteins are relatively resistant under the experimental conditions (pH 6.0). The increased susceptibility of these bonds in the rabbit protein appears to be related to the replacement of Gly‐46 by Ser and the change in the sequence immediately NH2‐terminal to Leu‐109, from Leu‐Ser to Thr‐Val. These cleavages of the rabbit protein at the four very susceptible bonds have permitted us to isolate peptides (1‐44), (45‐87), (88‐109), (110‐151), and (152‐168) in high yield. We have also isolated peptides (88‐151), (1‐14), and (15‐44) in low yield; the latter two result from limited cleavage at the relatively resistant Tyr14Leu15bond. Peptide (88‐109) has been chromatographically resolved into species differing in the degree of methylation of Arg‐105; this resolution is thought to result from differences in hydrogen

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02377.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:δ‐Aminolaevulinic acid (ALA) uptake into neurons and glia in primary culture as well as ALA toxicity and its effects on γ‐aminobutyric acid (GABA) uptake were examined. [4‐14C]ALA uptake into neurons and glia was nonsaturable, partially Na+‐ and temperature‐dependent, and appeared to comprise mainly diffusion into the cell. 2,4‐Dinitrophenol caused some inhibition of [4‐14C]ALA uptake whereas ouabain, KCN, or amino acids at 1 mM concentration were without effect. ALA (1 mM) caused a slight inhibition of [U‐14C]GABA uptake into neurons (14%) and glia (9%), but was without effect at lower concentrations. It is unlikely that, in acute porphyria, ALA reaches sufficiently high levels in nervous tissue to interfere with the reuptake of GABA into neurons or glia. ALA was shown to be toxic, judged by the loss of cells, to both neurons and glia at concentrations as low as 10 μM. Such a concentration of ALA may be expected to occur in the CSF of porphyric patients in the acute attack. However, results obtained with dispersed cells in culture may not necessarily reflect the situationin vivowhere the cell may have a far greater resistance to the effec

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02378.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY

摘要:

Abstract:Primary cultures of neurons and glial cells (astroblasts) prepared from brains of 8‐day‐old and 15‐day‐old chick embryos, respectively, were grown for periods between 3 and 19 days. Specific activity of lactate dehydrogenase (LDH) increased in both types of cultures as a function of time and was always significantly higher in glial cells than in neurons. Glial cell extracts were found to contain predominantly the anaerobic isoenzymatic form of LDH (LDH‐H4), and this pattern did not change over a period of 19 days. Cultured neurons contained predominantly the aerobic isoenzymatic form LDH‐H4, and there was a progressive appearance of all other isoenzymes over an 8‐day period. These results support the hypothesis of a different energy metabolism in neu

ISSN:0022-3042    

DOI:10.1111/j.1471-4159.1981.tb02379.x

出版商:Blackwell Publishing Ltd    

年代:1981

数据来源: WILEY