摘要:

AbstractStrychnine, a complex molecule, antagonizes in some unknown manner the action of glycine, an important inhibitory neurotransmitter in the spinal cord and brainstem of many vertebrates. To help understand the mechanism of this antagonism, we have employed modern computational methods to assess the similarities between these seemingly different molecules. An exhaustive comparison of topological and electronic features of both molecules was made. We have successfully located a glycine‐like fragment in the strychnine molecule that, when compared to glycine, exhibits both topological and electronic charge congruence. The successful location of this glycine‐like fragment allows us to speculate how the large strychnine molecule assumes its role as an antagonist against the inhibitory action of glycine, the simplest amino a

ISSN:0360-4012    

DOI:10.1002/jnr.490170302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractExtracts of injured rat brain contained molecules that shared biological and physicochemical properties with interleukin‐1 (IL‐1). Brain IL‐1‐like activity increased following brain injury in parallel with the increase in astrocyte and fibroblast mitogenic activity. After 3 days postlesion, it reached about 20 times the basal (noninjured) level. Monoclonal antibodies to human IL‐1 inhibited this brain IL‐1‐like activity.One of the cellular sources of brain IL‐1‐like activity seems to be astroglial cells. Primary cultures of purified rat brain astrocytes secreted into the culture medium more IL‐1 activity than comparable numbers of peripheral blood monocytes. Brain IL‐1, as well as authentic monocyte IL‐1, appear to act on brain glial cells, promoting thymidine incorporation into purifie

ISSN:0360-4012    

DOI:10.1002/jnr.490170303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe concentration of myelin basic protein (MBP) mRNA in primary cultures of cells dissociated from embryonic mouse cerebra and grown in the presence of varying amounts of thyroid hormone was measured using a32P‐labeled cDNA probe and a dot‐blot procedure. The cDNA probe contained 1.85 kilobases of the gene for MBP. The concentration of mRNA specific for MBP in control cells grown on a medium containing normal (euthyroid) calf serum increased with increasing age of culture. The greatest increase occurred between 15 and 35 days in culture (5.25‐fold increase); whereas between 35 and 50 days in culture, the rate of accumulation slowed to yield a net increase of MBP mRNA of only 10%. The quantity of MBP mRNA was drastically diminished at all ages studied when the cells were grown from the sixth day onward on a medium containing hypothyroid calf serum. Although the amount of MBP mRNA in hypothyroidtreated cells did increase, the change in concentration was less (3.43‐fold), and it peaked earlier (at 30 days). Unlike the euthyroid cells, after 30 days the MBP mRNA actually fell in the hypothyroid‐treated cells. If hypothyroid media were supplemented with triiodothyronine (T3) on the eighth day in culture, the quantity of MBP mRNA in the cells was restored almost completely to the levels found in the control euthyroid cells at all ages. Therefore, the regulation of the synthesis of MBP by thyroid hormone is at least in part a pretranslational event; that is, thyroid hormone adjusts the concentration of the mRNA specifi

ISSN:0360-4012    

DOI:10.1002/jnr.490170304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractHuman studies of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA‐S) have shown age‐related changes in serum levels of these two sex hormone precursors. The levels of both DHEA and DHEA‐S are characterized by monotonic decreases after puberty in females and after 20–24 yr of age in males. Further studies have shown that DHEA and DHEA‐S levels are significantly low or close to minimal at ages when the incidence of senile dementia of Alzeimer's type (SDAT) begins to increase. We propose that DHEA and DHEA‐S play a significant role in normal function of neuronal cells and that supplementation with them may prevent neuronal loss and/or damage. In the present study, using methods of immunocytochemistry, autoradiography, and scanning electron microscopy, we show that a supplement of as little as 10−8M DHEA or DHEA‐S greatly increases neuronal survival and differentiation and reduces astroglial proliferation rates in mouse brain cells in cultures. These results suggest that correcting the DHEA and the DHEA‐S deficit may prevent and/or improve the SDAT co

ISSN:0360-4012    

DOI:10.1002/jnr.490170305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe trophic effects of specific denervation on the growth and survival of fetal serotonergic (5‐HT) or norepinephrinergic (NE) neurons grafted into the hippocampus were assessed by means of two transplantation paradigms. In the first, fetal raphe cells (containing 5‐HT neurons) were transplanted into the control hippocampus. In the second, the transplantation was performed 2 weeks after the specific removal of 5‐HT afferents to the hippocampus with 5,7‐dihy‐droxytryptamine (5,7‐DHT). We found that a month after transplantation, the number of 5‐HT immunoreactive neurons was not significantly different between the two experimental paradigms. However, transplanted raphe neurons had 400% more 5‐HT synaptosomal high‐affinity uptake and 380% higher content of 5‐HT in the hippocampus with prior 5,7‐DHT lesion than in control hippocampus. Furthermore, immunocytochemistry showed that the transplanted 5‐HT neurons had denser processes and varicosities in the hippocampus with lesion than in control hippocampus. The somatic area of the neurons with these denser processes and varicosities was 42% larger than that of control group. A greater 5‐HT level could be achieved if transplanted neurons in the control hippocampus were treated with the supernatant extracted from the hippocampus with 5,7‐DHT lesion.In contrast, the NE level of the implanted fetal locus ceruleus (containing NE neurons) was not significantly higher in the 5‐HT denervated hippocampus than in control hippocampus a month after transplantation. These results suggest that 5‐HT denervation in the hippocampus induces a trophic substance which promotes the maturation rather than survival of

ISSN:0360-4012    

DOI:10.1002/jnr.490170306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractMembrane‐bound calmodulin increases following dopaminergic supersensitization of the rat striatum. To assess the generality of this relationship, mice were treated with two different supersensitization paradigms. Calmodulin levels and subcellular distribution were determined by radioimmunoassay. Chronic haloperidol treatment increased striatal D2dopamine receptor density by 25% but had no effect on membrane‐bound calmodulin levels. Similarly, 6‐hydroxy‐dopamine (6‐OHDA) lesions depleted striatal dopamine content>95% without affecting membrane‐bound calmodulin. In contrast, soluble calmodulin levels decreased by 15% in the 6‐OHDA‐lesioned striatum, suggesting that soluble calmodulin is enriched in presynaptic dopaminergic terminals. We conclude that dopaminergic supersensitization can occur in the mouse striatum in the absence of any change in calmodul

ISSN:0360-4012    

DOI:10.1002/jnr.490170307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe distribution of cerebellar gangliosides was studied in adult (73 ± 2 days) nervous (nr/nr) mutant mice which lose 50–90% of their Purkinje cells. This neuronal loss is associated with significant reductions in cerebellar weight and ganglioside concentration. The cerebellar dry weights (mg) and the ganglioside concentrations (μg N‐acetylneuraminic acid per 100 mg dry weight) innr/nrmice and age‐matched normal littermates (+/?) are 7.4 ± 0.3 mg and 13.2 ± 0.4 mg; and 411.7 ± 4.8 μg and 438.5 ± 2.1 μg, respectively. Abnormalities were also observed for the concentration of certain ganglioside species. Most notably, GT1a is significantly reduced by 42%, and GD3 is significantly increased by 29% in thenr/nrmice compared to the +/? mice. Thenr/nrmice also express a slight but significant reduction in GT1b. No ganglioside abnormalities were observed between thenr/nrand +/? mice in cerebral cortex. We previously found reduced cerebellar GT1a content in other mutants that also lose Purkinje cells, i.e.,sg/sg, pcd/pcd, andLc/+. GT1a is not reduced, however, inwv/wvmice that lose mostly granule cells. The findings innr/nrmice are therefore consistent with our hypothesis that GT1a is enriched in Purkinje cells. GD1a, which is enriched in mature granule cells, is not reduced in thenr/nrmice. Since we previously found that GD3 is a good marker for reactive glia in neurological disease, the elevated GD3 concentration in thenr/nrmice indicates a mild gliosis. Our findings withnr/nrand the other neurological mutants indicate that gangliosides can be useful as cell‐surface markers for monitoring changes in the cytoarchitecture of the m

ISSN:0360-4012    

DOI:10.1002/jnr.490170308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractThe basement membranes of the innervated surface of the electric organ ofDiscopyge tschudiipresent a high concentration of mucopolysaccharides as revealed by intense ruthenium red‐positive reaction. Glycosaminoglycans (GAGs) were isolated and characterized from these pure basement membranes by using a combination of agarose gel electrophoresis and enzymatic degradation with specific enzymes. The isolated basement membrane showed a high concentration of GAGs (130 mg/g of dry tissue); of this amount 49% was hyaluronic acid, 24% was chondroitin‐6‐sulfate, 12% was heparan sulfate, and 14% was dermatan sulfate. Controlled digestion with heparinase and heparitinases I and II was used to study the structural features of the heparan sulfate. Four unsaturated disaccharide units were found in the heparan sulfate: disulfated, N‐sulfated, N‐acetylated, and N‐acetylated O‐sulfated disaccharides. The disaccharide units of the cholinergic heparan sulfate present a high amount of disulfated disaccharides and a low amount of N‐acetylated O‐sulfated disaccharides. The N‐sulfated disaccharides, in contrast to the N‐acetylated ones, were found through all the structure of the cholinergic heparan sulfate. Finally our work shows for the first time the presence of dermatan sulfate in the basal lamina

ISSN:0360-4012    

DOI:10.1002/jnr.490170309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractPrimary cultures derived from adult mouse dorsal root ganglia have been maintained in the presence or absence of 5 × 10−6M cytosine arabinoside for periods of up to 4 weeks. In cultures in which cytosine arabinoside is present, the non‐neuronal cell population is effectively reduced. When uncoated plastic substrata are used there is also a concurrent decrease in the number of neurons if the medium is supplemented with cytosine arabinoside. The effects on neuron survival of substrata coated with fibronectin, polyornithine, polylysine, and exudates prepared from mouse liver cells were studied. It was shown that neuronal densities similar to those with uninhibited media may be retained in the presence of cytosine arabinoside if fibronectin‐coated substrata are prepared. With the other coating agents neuronal survival was also enhanced but to a lesser extent. The study offers a means therefore of producing purer cultures of dorsal root ganglia neurons than has previously been possible from adult mammalian s

ISSN:0360-4012    

DOI:10.1002/jnr.490170310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY

摘要:

AbstractA comparison was made of acute and chronic effects of ammonia on production of14CO2from the [U‐14C] labeled branched‐chain amino acids (BCAA) leucine, isoleucine, and valine as well as from [1‐14C] leucine, and on the incorporation of radioactivity from these amino acids into a perchloric‐acid‐precipitable protein fraction in astrocytes and neurons in primary cultures.Acute exposure of astrocytes to 3mM ammonium chloride suppressed14CO2production from [U‐14C] BCAA and especially from [1‐14C] leucine. This inhibitory effect was abolished or even reversed ([U‐14C] leucine) after chronic exposure to ammonia. Analogously, incorporation of radioactivity into the protein fraction was inhibited after acute exposure but not after chronic exposure of astrocytes to ammonia. The total protein content per culture was increased after chronic exposure. In neurons, production of14CO2and incorporation of14C into proteins were less affected than in astrocytes. These results are discussed in relation to the ability of the two cell types to synth

ISSN:0360-4012    

DOI:10.1002/jnr.490170311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1987

数据来源: WILEY