摘要:

AbstractThe study examines the effects of polyamines on growth of cultured neurons from 6‐day‐old rat cerebellar cortex, by means of: (a) irreversible inhibition of ornithine decarboxylase activity with α‐difluoromethylornithine, and (b) treatment with the exogenous diamine putrescine and the polyamines spermidine and spermine, in the presence of sera from different sources. Inhibition of ornithine decarboxylase activity starting at plating time led after 24 hr to a partial inhibition of cell aggregation with a drastic (90%) inhibition of neurite formation. However, after 48 hr of enzyme inhibition aggregation and neurite formation increased to approach the 24 hr control values and eventually cultures fully recovered. Polyamines added at plating time in the presence of fetal calf serum led to a permanent dose‐dependent inhibition of aggregation and neurite formation, spermine being effective at lower doses (spermineputrescine). The polyamine effects were observed in the presence of fetal calf, heat‐inactivated fetal calf and human sera, but not with rat serum. Addition of polyamines to 24‐hr‐old cultured neurons, in the presence of fetal calf serum, led 12 hr later to cell death. This lethal effect could be inhibited by aminoguanidine. We conclude: (a) irreversible inhibition of ornithine decarboxylase activity delays but does not prevent neuronal growth in culture; (b) oxidation products of extracellular polyamines inhibit cell aggregation and neurite formation of cultured neuroblasts, and have lethal effects on growing neurons in culture, and (c) different pharmacological effects of polyamines can be expected in different species.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90059-6

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractWe compared the rate of protein synthesis in immature and adult rat brainIn vivoto that in brain slices. After the incorporation of a flooding dose of [14C]valine,In vivoand in brain slices, the label in proteins was measured in CNS regions and in neuron‐ and glia‐enriched fractions. In regionsIn vivoin the adult, incorporation rates in corpus callosum were lower than in other regions, which were similar: in the young, cerebellum showed the highest rates and hypothalamus and cord the lowest. Since hypothalamus and cord were low in the young, there was no change during development in these two areas; in other areas incorporation rates in young were 2–3 times higher than in adult brain proteins. Incorporation rates in slices were lower thanIn vivo. In the young, cerebellum, olfactory bulb, and cord were close toIn vivo, and other areas in slices from young incorporated at 60–90% ofIn vivorates. In adult slices incorporation was 5–15% of thatIn vivoexcept in olfactory bulb, where it was 30%. In the cellular fractions, incorporationIn vivoin young was close in the neuronal and glial fractions; in adults incorporation rates in neurons were higher, as the decrease in development was less in neurons than astrocytes. In slices in young, astrocytes incorporated amino acids at 100% of theIn vivorates, neurons at 60%; in adult slices, incorporation was at only 4–7% of theIn vivorate.The results show that developmental changes in protein metabolism occur in all brain areas and brain cells, with metabolic rates in young 2–3 times that in adult. Incorporationin vitrois less thanIn vivo: it is close in immature tissue, but is greatly decreased in adult. Although developmental and postmortem differences in rates of synthesis affect most areas and cells, regional and cellular heterogeneity can be found.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90060-2

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractIn the mammalian organism putrescine is formed by two reactions: (a) decarboxylation of ornithine and (b) degradation of spermidine via the so‐called interconversion pathway. The latter comprises N1‐acetylation of spermidine by a cytosolic acetyltransferase. and oxidative splitting of N1‐acetylspermidine to putrescine by polyamine oxidase (PAO). It has previously been shown that specific inhibition of PAO causes a time‐dependent accumulation of N1‐acetylspermidine in brain, which is a measure of spermidine turnover. Another consequence of PAO inhibition is the decrease of brain putrescine concentration, proportional to its normal formation from spermidine. This observation allowed us to demonstrate the increasing significance of polyamine interconversion with brain maturation. The results support our hypothesis that the mechanisms which regulate cellular polyamine concentrations change during normal brain maturation from a system in whichl‐ornithine decarboxylase is dominating to a more sophisticated system in which both synthetic and catabolic processes become equally important regulatory factors.In contrast with current views, the activity ofS‐adenosylmethionine decarboxylase rather than that of ornithine decarboxylase limits the rate of polyamine biosynthesis during early brain development. In the mature brain the total amount of putrescine, which is formed both by decarboxylation of ornithine and by degradation of spermidine, limits the rate of spermidine formation. Changes of the regulatory system analogous to those described in this work are presumably not exclusive for brain, but rather characteristic for a variety of differentiating cells.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90061-4

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractNeurogenesis in the rat olfactory peduncle was examined with [3H]thymidine autoradiography. Animals in the prenatal groups were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H]thymidine on embryonic days (E) E13–E14, E14–E15, … E21–E22, respectively. One group of postnatal animals was given four consecutive injections of [3H]thymidine on postnatal days (P) P0‐P3. On P60, the percentage of labeled cells and the proportion of cells originating during either 24 or 48 hr periods were quantified at seven anatomical levels through both the anterior olfactory nucleus and the transition areas. A caudal (older) to rostral (younger) neurogenetic gradient is found both within and between structures in the olfactory peduncle. Neurons in the dorsal, lateral, and ventral‐lateral transition areas are generated mainly between E14 and E19, those in the anterior olfactory nucleus mainly between E15 and E21. Only 3–4% of the neurons in the most anterior pars lateralis and pars dorsalis originate after birth. All parts of the anterior olfactory nucleus show a strong superficial (older) to deep (younger) neurogenetic gradient (the “outside‐in” pattern). In contrast, neurons in the ventral—lateral transition area and in the dorsal transition area originate in a deep to superficial neurogenetic gradient (the “inside‐out” pattern), suggesting that these areas are, in reality, primary olfactory cortex. The lateral transition area is truly “transitional”, showing no neurogenetic gradient along the superficial‐deep plane. The medial transition area originates between E15 and E19 in a center (older) to edge (younger) “sandwich” neurogenetic gradient along the rostrocaudal plane, a pattern apparently unrelated to neurogenetic gradients in other olfactory peduncle structures. These data suggest that characteristic patterns of neurogenesis, namely the “insideout” vs the “outside‐in” gradients, permit the assignment of different structures to cortical vs ganglionic cytoarchitectonic components of the olfactory relay system.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90062-6

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractNeurogenesis in the rat primary olfactory cortex was examined with [3H]thymidine autoradiography. The experimental animals were the offspring of pregnant females given an injection of [3H]thymidine on two consecutive gestation days. Nine groups of embryos were exposed to [3H] thymidine on E13–E14, E14–E15, … E21–E22, respectively. On P60, the percentage of labeled cells and the proportion of cells originating during 24 hr periods were quantified at selected anatomical levels of the anterior and posterior piriform cortex, dorsal lateral peduncular cortex, and posterior two‐thirds of the ventral agranular insular cortex. Throughout most of the primary olfactory cortex, deep cells are generated earlier than superficial cells: the ‘dinside‐out’ pattern. Neurons in the anterior (prepiriform) cortex are located lateral to the caudal anterior olfactory nucleus and olfactory tubercle, and are generated mainly between E14 and E18 in a caudal (older) to rostral (younger) neurogenetic gradient. Neurons in the posterior (periamygdaloid) cortex are located lateral to the caudal olfactory tubercle and amygdala, and are generated mainly between E14 and E17 simultaneously along the rostrocaudal plane. Superficial cells in the piriform cortex have some additional neurogenetic gradients; ventromedial cells forming transition zones with either the olfactory tubercle or amygdala originate earlier than cells located dorsally and laterally. In the posterior piriform cortex, younger neurons are located at middle dorsoventral levels while older neurons lie above and below. Neurons in the dorsolateral peduncular cortex originate between E14 and E20 in a caudal to rostral gradient of neurogenesis; caudal parts also have a lateral to medial neurogenetic gradient. The most lateral part of the dorsolateral peduncular cortex is unique and does not have the typical ‘inside‐out’ cortical neurogenetic gradient. Neurons in the ventral agranular insular cortex (area 13) originate mainly between E15 and E17 in combined caudal to rostral and ventral to dorsal neurogenetic gradients. The neurogenetic gradients in the primary olfactory cortex, along with patterns of neurogenesis throughout the olfactory projection field are related to the termination patterns of afferents from the main olfactory bulb.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90063-8

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractDevelopmentally regulated modifications of glycosaminoglycans (GAGs) in the central nervous system (CNS) have suggested that also in the CNS, these compounds might participate in morphogenesis and nerve cell differentiation. However very few studies have been reported concerning the regional distribution of these compounds by histochemical techniques. We have used the Alcian Blue staining method also in conjunction with enzymatic digestion and with a technique which allowed the measurement of the degree of GAG sulphatation. The combination of the three techniques showed that during the first week GAGs, presumed to be hyaluronic acid, are localized throughout the neuropile of the entire cerebellum and especially in the medullary region. Sulphated glycans appear later in the medullary region (particularly at the border between the medullary region and the internal granular layer) and in all the layers of cerebellum (in particular around the Purkinje and deep cerebellar nuclei neurons and possibly in the cerebellar glomeruli). Sulphated glycans in the medullary region disappear around the 12th day when myelination starts. The transient presence of glycoproteins in the molecular layer was also detected.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90064-X

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractExposure of organ cultures of newborn rat brains to tri‐iodothyronine (T3) followed by cell fractionation as well as direct exposure of prefractionated neuronal (N) and glial (G) cells to the hormone results in an almost selective induction of tubulin in the glial cells. This is established from two independent assays of tubulin, viz. colchicine binding and vinblastin precipitation. In the newborn rat brain, the tubulin content of the G cells is almost 3‐fold higher than that of the N cells. Treatment with T3elicits 40–50% stimulation of tubulin in the G cells within 2 hr without any significant increase in the N cells. Brains from 8‐ or 50‐day‐old rats are irresponsive to induction to tubulin by T3. The rate of incorporation of [3H]leucine into total protein is very similar in both N and G cells of newborn rat brain but that into tubulin of G cells is about 3‐fold higher than that of N cells. T3promotes this incorporation by over 30% in the G cells with only a marginal 5% increase in the N cells. The overall results suggest that the glial cells represent the target cells for the T3‐induced synthesis of tubulin, the major structural protein of the developing brain.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90065-1

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractNeuron‐enriched cultures derived from 6‐day‐old chick embryo cerebral hemispheres were treated with morphine or methadone, 10−5M or 10−6M, on days 4–6 or 6–8 in culture and were evaluated morphologically and biochemically at day 9 using phase contrast microscopy and choline acetyltransferase activity (ChAT) as a cholinergic marker. The treatment of the cultures with morphine markedly affected their growth pattern; specifically, we observed an increased number of flat cells presumptively glia, and aggregates sided by flat cells and devoid of thick bundles of neuritic processes that normally characterize neuron‐enriched cultures. These morphologic changes were reflected in a drastic decrease of ChAT activity in cultures treated from day 4 to day 6 but not from 6 to 8. In contrast to morphine, exposure to 10−6M methadone from day 4 to day 6 resulted in reduced ChAT activity but the growth pattern of the cultures remained morphologically intact. We suggest that morphine exerts a general neurotoxic effect whereas methadone may affect some specific cholinergic function.

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90066-3

出版商:Wiley    

年代:2003

数据来源: WILEY

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90067-5

出版商:Wiley    

年代:2003

数据来源: WILEY

ISSN:0736-5748    

DOI:10.1016/0736-5748(86)90068-7

出版商:Wiley    

年代:2003

数据来源: WILEY