摘要:

AbstractIron‐saturated transferrin is a ubiquitous growth factor that plays a critical role in cellular iron uptake, growth and proliferation. Here we have studied the expression and distribution of transferrin receptors and iron uptake following injury of the rat sciatic nerve. Axotomy led to a massive but transient increase (days 2–9, maximum day 4) in [125l]transferrin binding at the site of the injury and in the distal, denervated part of the crushed or resected sciatic nerve, shortly preceding the time course of cellular proliferation (Friede and Johnstone,Acta Neuropathol,7, 218–231, 1967; Jureckaet al., Acta Neuropathol,32, 299–312, 1975). An additional, transient increase in specific binding was observed during reinnervation after reconnection of the resected sciatic nerve. Immunocytochemistry using the Ox‐26 monoclonal antibody revealed strong and simultaneous expression of the transferrin receptor protein on two different cell types: on a subpopulation of blood‐borne macrophages invading the injured peripheral nerve and on Schwann cells reacting to denervation and reinnervation. In addition, studies using intravenously injected radioactive iron (59Fe3+) showed a massive increase in endoneural iron uptake confined to the lesion site and to the distal part of the axotomised sciatic nerve, parallel to the time course of reactive transferrin receptor expression. Since iron is an essential cofactor of a number of key enzymes needed in energy metabolism and DNA synthesis, these data suggest that the induction of transferrin receptor expression may play an important role in the regulation of cellular growth and proliferation during peripheral nerve r

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00027.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe release of arachidonic acid (ArA) metabolites from mouse neurons and astrocytes in primary culture has been studied in response to ionomycin or glutamate stimulation. Cells were preincubated with [3H] ArA for 24 h and the radioactivity released was examined by HPLC. In striatal, cortical and hippocampal neurons, glutamate and ionomycin strongly stimulated the release of ArA, but neither prostaglandins (PGs) nor hydroxyeicosatetraenoic acids (HETEs) could be detected. If they were released, these latter compounds represented50% of the [3H]ArA was metabolized to PGF2α, PGE2, PGD2, HHT, 15‐ and 11‐HETE in cultured astrocyte homogenates, no [3H]ArA metabolism could be detected in cultured striatal neuron homogenates. Moreover, neuronal homogenates did not inhibit the metabolism of [3H]ArA observed in either astrocyte or platelet homogenates. These results indicate that central neurons in primary culture possess very low lipoxygenase and cyclooxygenase activities. They emphasize the need to identify the cellular source of ArA metabolites in the brain, particularly when considering the multiple new messenger roles proposed for these molecules, such as that of retrograde messengers involved in syna

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00028.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractWe have used the techniques of microdialysis andin vivovoltammetry to monitor striatal dopamine and ascorbate, as well as motor activity in unanaesthetized, freely‐moving rats. Systemic administration of the non‐selective dopamine receptor agonist apomorphine (0.5 mg/kg, s.c.) caused a decrease in dopamine, an increase in ascorbate, stereotyped behaviour and a generalized increase in motor activity. Separate systemic applications of the D2receptor agonist SKF 38393 (10 mg/kg, s.c.) and the D2receptor agonist Quinpirole (0.1 mg/kg s.c.) caused a decrease in dopamine but had no effect on ascorbate or motor activity. After coadministration of these drugs, there was an increase in both ascorbate and motor activity. Local application of apomorphine (0.01 mM) caused a reduction in dopamine similar to that seen following systemic application but had no effect on ascorbate or motor activity. The present results demonstrate that dopamine, via D1and D2receptors outside the striatum, plays an important role in the control of ascorbate release. These results lend further support to the hypothesis that changes in ascorbate levels are an index of glutamatergic neurotransmiss

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00029.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe changes in local cerebral glucose utilization (LCGU) and neuronal unit activities in the subthalamic nucleus and its major target structures (the pars reticulata of the substantia nigra, the globus pallidus and the entopeduncular nucleus) following microinjection of a GABAergic antagonist (bicuculline methiodide, 0.08 nmol) or agonist (muscimol, 0.2 nmol) into the subthalamic nucleus were determined. The metabolic effect was assessed by measuring LCGU by quantitative [14C]‐2‐deoxyglucose autoradiography in ketamine‐anaesthetized rats. Bicuculline methiodide induced increased LCGU in the ipsilateral globus pallidus, the entopeduncular nucleus and the substantia nigra pars reticulata. In contrast, muscimol decreased LCGU in these structures. The neuronal activities in the subthalamic nucleus and related structures increased following injection of bicuculline and decreased after injection of muscimol. The changes in LCGU within the structures directly related to the subthalamic nucleus were correlated with the changes in the unit activity either in the subthalamic nucleus and/or its projection structures. However, the amplitude of the relative changes in neuronal unit activity were greater than the changes in LCGU. Nevertheless, the results emphasize the functional role of the subthalamic nucleus as an activating structure within the basal ga

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00030.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractNorthern blot analysis was used to demonstrate high levels of hippocampus‐derived neurotrophic factor/ neurotrophin‐3 (HDNF/NT‐3) mRNA in the embryonic day (E) 13–14 and 15–16 spinal cord. The level decreased at E18–19 and remained the same until postnatal day (P) 1, after which it decreased further to a level below the detection limit in the adult.In situhybridization revealed that the NT‐3 mRNA detected in the developing spinal cord was derived from motoneurons and the decrease seen at E18–19 was caused by a reduction in the number of motoneurons expressing NT‐3 mRNA. The distribution of NT‐3 mRNA‐expressing cells in the E15 spinal cord was very similar to the distribution of cells expressing choline acetyltransferase or nerve growth factor receptor (NGFR) mRNA. Moreover, a striking similarity between the developmentally regulated expression of NT‐3 and NGFR mRNA was noted in spinal cord motoneurons. A subpopulation of all neurons in the dorsal root ganglia expressed brain‐derived neurotrophic factor (BDNF) mRNA from E13, the earliest time examined, to adulthood. These results are consistent with a trophic role of NT‐3 for proprioceptive sensory neurons innervating the ventral horn, and imply a local action of BDNF for developing sensory neurons wit

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00031.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractIntracellular recordings and current and single‐electrode voltage‐clamp techniques were used to study the membrane responses of CA1 pyramidal neurons to bath application of L‐homocysteic acid (L‐HC) in the rat hippocampal slice preparation. In control artificial cerebrospinal fluid (ACSF), L‐HC (25 ‐ 250 μM) depolarized the membrane and induced a burst‐like firing pattern. Both the membrane depolarization and the burst firing were blocked by theN‐methyl‐D‐aspartic acid (NMDA) receptor antagonists D‐(‐)‐2‐amino‐5‐phosphonovaleric acid (AP‐5, 50 μM), D‐(‐)‐2‐amino‐7‐phosphonoheptanoic acid (AP‐7, 50 μM) and (±)‐3‐(2‐carboxy‐pipera‐zin‐4‐yl)‐propyl‐1‐phosphonic acid (CPP, 20 μM). In ACSF containing tetrodotoxin (1 μM), L‐HC (100–300 μM) induced at resting membrane potential a depolarization which was associated with a small increase in input conductance. These effects were unaffected by 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX, 10–20 μM) but were fully blocked by AP‐5, AP‐7 (50 μM) and CPP (10–20 μM). In voltage‐clamp experiments, L‐HC induced slow inward currents which were voltage‐dependent between ‐ 70 and ‐ 30 mV and reversed polarity near 0 mV. The L‐HC‐induced inward current was unaffected by CNQX (10–20 μM) but was strongly reduced by AP‐5 or AP‐7 (50 μM).The L‐HC‐induced inward current was temperature‐dependent. Between ‐60 and ‐70 mV, its amplitude increased by 320% when the temperature was lowered from 33 to 22°C. The L‐HC‐induced current was also potentiated by the specific L‐HC uptake blockerβ‐p

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00032.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractUnilateral lesions of the rat frontal cortex were made either alone or in combination with the caudate‐putamen in order to examine (a) their morphological influence on the substantia nigra and (b) their neurochemical influence on GABA function in the superior colliculus. One to two months following the combined lesion, neuronal somata in the ipsilateral pars reticulata of the substantia nigra were clearly hypertrophied (+ 30%). Morphological changes in the substantia nigra were not evident contralateraly or in animals bearing only cortical lesions. One to two months following cortex‐only lesions, no significant alterations in tectal GABA concentration were observed. However, the combined lesion induced elevations of GABA within both the medial and lateral sectors of the intermediate and deep layers of the superior colliculus. This effect was restricted to the ipsilateral side and was most pronounced in lateral sectors. The vast majority of GABA released from superfused control tectal slices by a depolarizing stimulus (35 mM KCI) was calcium‐dependent. Such evoked GABA release from ipsilateral tectal slices was significantly reduced (‐25%) by unilateral lesions of the substantia nigra, a structure that is known to provide GABA‐containing inputs to the tectum. In contrast, cortical lesions alone significantly enhanced the evoked tectal GABA release (+ 66%), although their influence was again confined to the ipsilateral side. Combined lesions of the cerebral cortex and caudate‐putamen significantly enhanced the evoked GABA release from tectal slices in both hemispheres but the changes were most marked ipsilaterally (+ 147%). It is suggested that the hypertrophy of GABA‐containing nigrotectal somata seen after removal of corticostriatal, corticotectal and in particular GABA‐containing striatonigral fibres may reflect concomitant increases in GABA synthesis within and/or sprouting of nigrot

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00033.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

In α‐chloralose‐anaesthetized, spinalized cats we examined the effects of NMDA antagonists on the discharges of 71 spinal neurons which had afferent input from the knee joint. These neurons were rendered hyperexcitable by acute arthritis in the knee induced by kaolin and carrageenan. They were located in the deep dorsal and ventral horn and some of them had ascending axons. TheN‐methyl‐d‐aspartate (NMDA) antagonists ketamine andd‐2‐amino‐5‐phosphonovalerate (AP5), were administered ionophoretically, and ketamine was also administered intravenously. In some of the experiments the antagonists were tested against the agonists NMDA and quisqualate. The effects of the NMDA antagonists consisted of a significant reduction in the resting activity of neurons and/or the responses of the same neurons to mechanical stimulation of the inflamed knee. Intravenous ketamine was most effective in suppressing the resting and mechanically evoked activity in 25 of 26 neurons tested. Ionophoretically applied ketamine had a suppressive effect in 11 of 21 neurons, and AP5 decreased activity in 17 of 24 cells. The reduction in the resting and/or the mechanically evoked discharges was achieved with doses of the antagonists which suppressed the responses to NMDA but not those to quisqualate. These results suggest that NMDA receptors are involved in the enhanced responses and basal activity of spinal neurons induced by inflammatio

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00034.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractCalcium influx through voltage‐activated calcium channels may play a crucial role in the propagation and maintenance of seizure activity. We have examined the contribution of various types of calcium currents to epileptogenesis by studying the effects of various calcium channel blockers on epileptiform activity.N‐methyl‐d‐aspartate receptor‐mediated epileptiform activity was induced by removal of magnesium ions superfusing the cortex, or by low‐frequency stimulation of the underlying white matter. CoCl2, CdCl2and ω‐conotoxin, acting at the N‐ and L‐type calcium channels, significantly reduced epileptiform activity. L‐channel antagonists nifedipine and verapamil, and the agonist BAY K 8644, increased spontaneous bursting in cortical wedges, but had no effect upon evoked activity. The T‐channel blocker NiCI2had variable effects on epileptiform activity, whereas phenytoin consistently reduced such activity. These results suggest that calcium influx underlying epileptiform activity in the rat neocortex may occur at least partially via the activation of the N‐type calcium channel. However, contributions from other calcium channel

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00035.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY

摘要:

AbstractThe possibility that the dopaminergic neurons innervating the medial prefrontal cortex (mPFC) can inhibit locomotor behaviour has been suggested in several studies. The evidence remains indirect, however, because the manipulations tested aimed exclusively at permanently depleting mPFC dopamine. Here we demonstrate in rats that acute increases in dopamine transmission in this site by local injections of amphetamine inhibit the known locomotor‐activating effects of amphetamine in the nucleus accumbens (N.Acc). Further, intra‐mPFC injections of the D‐1 dopamine receptor antagonist SCH‐23390, but not other dopamine antagonists with greater affinities for noradrenergic, serotonergic and D‐2 dopamine receptors, enhanced the locomotion induced by intra‐N.Acc. amphetamine. These findings provide direct evidence for the inhibition of locomotor activity by mPFC dopamine and suggest that it is acting at D‐1 dopamine receptors

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1991.tb00036.x

出版商:Blackwell Publishing Ltd    

年代:1991

数据来源: WILEY