摘要:

AbstractPrevious studies in rats have demonstrated both the link between voltage‐operated calcium channels and endothelin and their cerebral involvement in the pathophysiology of spontaneous hypertension. In the present study, the interaction of endothelin with specific dihydropyridine (DHP) binding sites was investigated using the brain slices model. In rat hippocampal slices, pre‐incubation with Bay K 8644 decreased [3H] (+) PN 200‐110 binding. There was no difference in agonist‐induced decrease of DHP binding in normotensive and spontaneously hypertensive (SH) rats. The effect of Bay K 8644 was partially inhibited by endothelin but not by angiotensin in both normotensive and hypertensive rats. These data compared to those of other studies suggest that DHP binding sites which are regulated by endothelin are post‐synaptic. We conclude that brain slices provide a goodin vitromodel to study DHP receptor regulation and to explore endothelin interactions with DHP‐sensitive Ca2+channels.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90001-T

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractTo evaluate the effect of partial denervation on age changes, morphological and physiological parameters were studied in young versus old extensor digitorum longus (EDL) muscles. The aims of this study were to elucidate synaptic maintenance in general and specifically to assess the adaptability of motor neurons from young and old animals to an enlarged field of innervation. Partial denervation was carried out in two groups of 30–40 g mice, aged within 6 or 24 months, by sectioning of the nerve supplying EDL muscle under methoxyfluorane anaesthesia. Sham operations were carried out on additional animals which served as controls. Five weeks' post‐surgery, the safety factor of synaptic transmission was estimated by dividing the nerve‐evoked twitch tension generated in 1 mM Ca2+Krebs by that generated in 2.5 mM Ca2+Krebs. Low Ca2+Krebs caused a more pronounced decline in twitch tension in young control EDL muscles than old control. After partial denervation, young EDL twitch tensions were not significantly different while old were 20% of those in normal Krebs. Zinc Iodide Osmium (ZIO) stained nerve terminal parameters were significantly increased with aging. After partial denervation, nerve terminal areas were 46 and 39% larger in young and old mice, respectively, compared to their corresponding controls. Present data suggest that motor neurons of old mice are unable to develop and maintain an enlarged field of innervation.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90002-U

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractGrowth factors play a central role in the regulation of normal and injury‐induced regenerative cell growth. The purpose of this article is to summarize the available data on the expression of different growth factors and their receptors in the injured peripheral nervous system and to discuss their possible role in promoting peripheral nerve regeneration.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90003-V

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe distribution of the retinoid‐inducible enzyme, tissue transglutaminase (tTG) in developing rat spinal cord was determined by enzyme assay and immunocytochemistry. tTG activity was at its highest in the forebrain in late foetal development. In hindbrain and spinal cord, elevated activity persisted until after birth. In spinal cord only, a second peak of activity occurred during the first weekpost partum(P3). tTG was associated with both the cytosolic and particulate tissue fractions throughout spinal cord development, but the particulate component was more prominent in the early postnatal period. tTG was more concentrated during this period in the ventral horn, where the particulate‐associated enzyme activity was highest. In spinal cord at 3 dayspost partum, particulate tTG could be solubilized with lubrol‐PX, dithiothreitol and potassium thiocyanate. Both soluble and particulate‐associated tTG coeluted with guinea‐pig liver transglutaminase C by DEAE‐sephacel chromatography. The first peak of tTG activity during late foetal life coincided with the transient localization of the enzyme by immunocytochemistry in vascular endothelia throughout the spinal cord. The second peak of activity at 3 dayspost partum, by which time vascular immunoreactivity was absent, coincided with the occurrence of small numbers of intensely immunoreactive motor neurones in the ventral horn. Immunoreactive motor neurones were seen predominantly at two levels: the lower thoracic segments and lumbar enlargement. The abnormal appearance of many immunoreactive neurones suggested degenerative changes were occurring. tTG was also present in central canal cluster cells from birth onwards. No neuronal immunoreactivity was seen throughout foetal development. A proportion of motor neurones prepared from E15 spinal cord and grown in coculture with spinal cord astrocytes, were immunoreactive for tTG. All immunoreactive neurones showed signs of degeneration. Addition of myotube‐conditioned medium (a source of cholinergic differentiation factor, CDF) reduced the proportion of tTG‐immunoreactive neurons in the cultures. Schwann cell‐conditioned medium (a source of ciliary neurotrophic factor, CNTF) had a similar but less potent effect on the numbers of immunoreactive neurones. The possibility that tTG is a marker for late, but not early‐phase programmed cell death in the developing rat spinal cord is discussed in the light of a proposed role for tTG in the mechanism of natural cell death by apoptosis.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90004-W

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe plasma membranes of several mammalian tissues including the brain are known to have specific binding sites for glucocorticoids. The developmental changes in specific glucocorticoid binding to synaptic plasma membrane (SPM) from rat brain were determined at various postnatal ages, using [3H]triamcinolone acetonide (TA) as the steroid ligand. The specific binding of the labeled glucocorticoid to SPM during the first 2 postnatal weeks was only 40% of the adult level. An increase of the specific binding occurred after day 15 and this developmental rise of binding reached the adult level approximately by the end of the fourth week. Methodologically, these developmental data are detailed in the present article to include nonspecific binding as well as specific binding. Scatchard analysis indicates that the developmental rise of the specific glucocorticoid binding was due to an increase in the membrane binding sites. The ontogenetic increase of membrane binding sites during postnatal brain development provides additional evidence that these binding sites have physiological significance in brain function.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90005-X

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractNormal human (week 17–20) and rat (E16–17) amniotic fluids were used as culture media for primary cultures of rat fetal (E 16) cortical, mesencephalic and striatal cell dissociates, or astroglial subcultures from the same brain regions. Phase‐bright and dark cells were identified under phase contrast microscopy and their cell processes were measured utilizing semi‐automated procedures. Subcultured astroglia were immuno‐reacted against glial fibrillary acidic protein and fibronectin. Rat and human amniotic fluid allowed survival and growth of neuronal and non‐neuronal cells. Human amniotic fluid samples were trophic in variable degrees. Cerebral cortex subcultured astroglia usually expressed a radial‐like morphotype. Although charcoal‐adsorbed human amniotic fluid was trophic for primary cultures, its ability to sustain neuritic growth depended on its degree of trophism before treatment. Growth of cell processes in neuronal‐ and glial‐like cells in primary cultures was inhibited to different degrees by the addition of antisera towards nerve or epidermal growth factors. It is concluded that amniotic fluid constitutes a trophic medium for astroglia and neurons. Both, nerve and epidermal growth factors appear to be necessary for growth of cell processes in neuronal and glial primary cultures in amniotic fluid. Trophic effect of amniotic fluid on subcultured astroglia did not seem to be diminished by nerve growth factor antiserum. The role of amniotic fluid during the early phases of brain organogenesis is discussed.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90006-Y

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractA variety of experimental evidence suggests that calmodulin and protein kinases, especially protein kinase C, may participate in regulating neurite development in cultured neurons, particularly neurite initiation. However, the results are somewhat contradictory. Further, the roles of calmodulin and protein kinases on many aspects of neurite development, such as branching or elongation of axons vs dendrites, have not been extensively studied. Cultured embryonic rat hippocampal pyramidal neurons develop readily identifiable axons and dendrites. We used this culture system and the new generation of highly specific protein kinase inhibitors to investigate the roles of protein kinases and calmodulin in neurite development. Neurons were cultured for 2 days in the continuous presence of calphostin C (a specific inhibitor of protein kinase C), KT5720 (inhibitor of cyclic AMP‐dependent protein kinase), KN62 (inhibitor of Ca2+‐calmodulin‐dependent protein kinase II), or calmidazolium (inhibitor of calmodulin), each at concentrations from approximately 1 to 10 times the concentration reported in the literature to inhibit each kinase by 50%. The effects of phorbol 12‐myristate 13‐acetate (an activator of protein kinase C) and 4α‐phorbol 12,13‐didecanoate (an inactive phorbol ester) were also tested.At concentrations that had no effect on neuronal viability, calphostin C reduced neurite initiation and axon branching without significantly affecting the number of dendrites per neuron, dendrite branching, dendrite length, or axon length. Phorbol 12‐myristate 13‐acetate increased axon branching and the number of dendrites per cell, compared to the inactive 4α‐phorbol 12,13‐didecanoate. KT5720 inhibited only axon branching. KN62 reduced axon length, the number of dendrites per neuron and both axon and dendrite branching. At low concentrations, calmidazolium had no effect on any aspect of neurite development, but at high concentrations, calmidazolium inhibited every parameter that was measured (including viability).These results suggest that these three protein kinases selectively modulate different aspects of neurite development. The universality of effects caused by calmodulin inhibition make it impossible to determine if there are specific targets of calmodulin action involved in neurite development. Finally, our data indicate that some superficially similar characteristics of neuronal differentiation, such as neurite initiation and branching, may be controlled by quite different molecular mechanisms.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90007-Z

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe postnatal development of laminar pattern ofm1‐,m3‐ andm4‐mRNA‐muscarinic acetylcholine receptor subtypes in the visual cortex of both normally raised and monocularly deprived rats (one eyelid sutured at the age of 11 days) was studied usingin situhybridization histochemistry and computer‐assisted image analysis. From birth until day 15 the level ofm1‐receptor transcript in layer II/III increases markedly as compared to deeper layers. From day 15 up to day 18 a transient bimodal pattern develops with peaks in layers II/III and VI. Already on day 35 a more homogeneous distribution ofm1‐receptor mRNA level is detectable persisting until adulthood. In contrast, them3‐receptor mRNA shows already at birth a bimodal distribution with peaks in layers II/III and VI. Further development until adulthood results in transient changes in the ratio of the mRNA levels in these layers. In the adult visual cortex a similar laminar pattern as at birth is observed. From day 1 up to day 10 a relative increase in the mRNA level of them4‐receptor in layers II to IV is observed. From day 10 until day 15 a bimodal distribution of receptor mRNA develops with peaks in layers III and VI which is similar to the adult stage. However, between days 18 and 35 a shift in the laminar receptor mRNA distribution occurs resulting in peaks in layers IV and VI. The labeling of them5‐receptor transcript in rat visual cortex was very weak and did not show any alteration with age.Unilateral eyelid closure from postnatal day 11 resulted in transient changes in the laminar distribution ofm3‐ andm4‐receptor mRNA between postnatal days 18 and 25, whereas the development of the laminar pattern of them1‐receptor mRNA was not affected regardless of the length of visual deprivation.The distinct laminar developmental pattern of mRNA muscarinic receptor subtypes in rat visual cortex suggests specific roles of the muscarinic receptor subtypes during the first weeks of postnatal maturation of visual function.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90008-2

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe present study was designed to ascertain septohippocampal cholinergic alterations and their related behavioral deficits after early exposure to ethanol. Mouse pups were exposed to ethanol, 3 g/kg by daily subcutaneous injection on postnatal days 2–14. At age 50 days, the ethanol‐exposed mice had significant reductions from control levels in eight‐arm maze performance. For example, on the fourth testing day, the number of correct entries in the ethanol group was 21% below control levels (P<0.05) and the number of trials needed to enter all arms was 48% above control (P<0.001). It took the ethanol‐exposed mice twice the time to reach criterion than it did control (P<0.01). A 33% increase from control level in muscarinic receptor number (βmax) was found in the treated mice of age 22 days and a 64% increase at age 50 days (P<0.001). However, no differences between control and treated groups could be detected in the presynaptic component of the cholinergic innervation, choline acetyltransferase activity. The results suggest that early ethanol exposure acts on hippocampal function similarly to phenobarbital, probably via alterations in postsynaptic processes in the septohippocampal cholinergic pathways.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90009-3

出版商:Wiley    

年代:2003

数据来源: WILEY

摘要:

AbstractThe temporal pattern of development and distribution of gamma aminobutyric acid, serotonin, substance P and neuropeptide Y immunoreactive profiles was studied in the human visual cortex from 16 to 26 weeks of gestation, using an immunohistochemical technique. The immunoreactive profiles showed an increase in number and a change in their morphology and distribution pattern over the time period studied. A large number of neurons, fibers and terminals were stained with GABA antibody at 17–18 weeks and were distributed throughout the five zones of the developing visual cortex. GABA neurons were non‐pyramidal and bipolar in form at 17–18 weeks while at 18–19 and 20–21 weeks the cells of subplate and intermediate zones were multipolar. Substance P and serotonin immunopositive fibers were present mainly in the intermediate zone at 16 and 17–18 weeks, where they were oriented in a horizontal manner. At subsequent ages they invaded the other zones also. Substance P positive neurons could be visualized only at 26 weeks of gestation in the intermediate, subventricular and ventricular zones; no cell bodies, however, stained with serotonin antibody. Neuropeptide Y immunoreactive cells and fibers were first seen in the intermediate zone but later were found to be distributed in other zones too. The observations indicate that the intermediate zone of the visual cortex in which the transmitters and peptides appear earlier assumes importance in the normal development as also noted in other mammals.

ISSN:0736-5748    

DOI:10.1016/0736-5748(93)90010-B

出版商:Wiley    

年代:2003

数据来源: WILEY