摘要:

AbstractThe present study was designed to evaluate the roles of serotonin 5‐HT1Aand 5‐HT2receptors in the effects of neuroleptic drugs in the paw test. This behavioural test has been shown to model both the antipsychotic efficacy as well as the extrapyramidal side‐effect liability of neuroleptic drugs. Whereas the 5‐HT1Areceptor agonist 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin (8‐OHDPAT) reduced the effects of the classical neuroleptic haloperidol, it increased the effects of the atypical neuroleptic clozapine. The 5‐HT2receptor antagonist ketanserin as well as the 5‐HT1C/5‐HT2receptor antagonist ritanserin, on the other hand reduced the effects of haloperidol, whereas the 5‐HT1C/5‐HT2receptor agonist 1‐(2,5‐dimethoxy‐4‐iodophenyl)‐2‐aminopropane (DOl) reduced the effects of clozapine. The most important finding, however, was that the behavioural effects of different (putative) neuroleptics (fluphenazine, SCH‐39166, remoxipride, prothipendyl, thioridazine and risperidone) were differentially influenced by both 8‐OHDPAT and DOl, suggesting that there are important differences between the neuronal mechanisms underlying the behavioural effects of these neuroleptic drugs, even within the subc

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00242.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractSome of the marked biochemical and electrophysiological changes provoked by section of the axon in mature neurons suggest that the intracellular calcium concentration ([Ca2+]i) may be increased. We have measured the [Ca2+]iusing the fluorescent indicator Indo‐1 microinjected into rat superior cervical ganglion neurons. No differences in resting [Ca2+]ilevels were found between control neurons and cells which had been axotomized 7–10 days before. However, the rise in [Ca2+]ievoked by orthodromic or antidromic stimulation and the recovery after the stimulating train were considerably slower in axotomized neurons than in control cells. We also found that the number of calbindin‐D28k‐immunopositive cells in the ganglion increases after axotomy, which could be related to the observed differences in calcium home

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00243.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractCortical neurons differ in their neurochemical properties. Projection neurons use excitatory amino acids as transmitters, most local interneurons contain the inhibitory transmitter GABA, and specific subtypes of local circuit neurons express distinct neuropeptides. How this cellular diversity is generated during development is not known. We have been studying the transmitter differentiation of cortical neurons in differentin vitrosystems using immunohistochemical techniques. Transmitter phenotypes of cortical neurons were examined in slice cultures, i.e. in the absence of extrinsic cortical connections, and in dissociated cortical cell cultures, i.e. in the absence of extrinsic and intrinsic cortical connections. The expression of vasoactive intestinal polypeptide in cortical interneurons occurred normally in slice cultures prepared from neonatal rats between birth and 2 days of age, but was strongly impaired in dissociated cell cultures prepared at the same time. These results suggest that the intact cortical environment present in the slice cultures exerts crucial influences for neuropeptide differentiation. In contrast, the transmitters glutamate and GABA were expressed normally in the appropriate cell types and similar in proportions in dissociated cell cultures prepared from cortices at embryonic day 19. Only cells dissociated during S‐phase failed to express glutamate and GABAin vitro.When cells were kept for 24 h after mitosis in a cortical slice preparationin vitro, however, they later expressed their appropriate transmitter phenotypes. Thus, signals from the local cortical environment that act early in the cell cycle are required for the specification of transmitter phenotypes of cortical neuron

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00244.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractModulation by exogenous and endogenous adenine nucleotides and adenosine of [3H]acetylcholine release evoked by veratridine (10 μM) was compared in synaptosomal fractions from the hippocampus and the cerebral cortex of the rat. In both brain areas, exogenously added ATP or adenosine (10–100 μM) inhibited the evoked tritium release. In the hippocampus, ATPμS, an ATP analogue more resistant to catabolism than ATP, was virtually devoid of effect on tritium release, and the effect of ATP was prevented by the ecto‐5′‐nucleotidase inhibitor α,β‐methylene ADP (100 μM), by adenosine deaminase (2 U/ml) and by the A1adenosine receptor antagonist 1,3‐dipropyl‐8‐cyclopentylxanthine (DPCPX, 20 nM). In contrast, in the cerebral cortex, the effect of ATP on tritium release was not prevented by either α,β‐methylene ADP (100 μM) or adenosine deaminase (2 U/ml), and several ATP analogues (30 μM) inhibited release. The order of intensity of the inhibitory effects of the ATP analogues was: ATPγS>ATP>ñ,γ‐imido ATP>β,γ‐methylene ATP>2‐methyl‐S‐ATP, α,β‐methylene ATP. The effect of ATPγS in the cerebral cortex was prevented by DPCPX (20 nM) and was not affected by the P2purinoceptor antagonist suramin (100 μM). In the hippocampus, α,β‐methylene ADP (100 μM) increased the evoked release of tritium, and adenosine deaminase (2 U/ml) produced an even greater increase; when adenosine deaminase was added in the presence of α,β‐methylene ADP, adenosine deaminase still increased the evoked release of tritium. In the cerebral cortex, DPCPX (20 nM) and adenosine deaminase (2 U/ml) increased the evoked tritium release by a similar magnitude, but the effect of adenosine deaminase was smaller than in the hippocampus. It is concluded that in the cerebral cortex ATP as such presynaptically inhibits acetylcholine release, whereas in the hippocampus the role of adenine nucleotides is as a source of endogenous extracellular adenosine that tonically inhibits acetylcholine release. The results also show that besides formation of adenosine from adenine nucleotides, released adenosine as such contributes in nearly equal amounts to the pool of endogenous adenosine that presynap

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00245.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractUsingin situhybridization, the expression of the mRNA for a neuropeptide Y (NPY) receptor, was studied in lumbar (L) 4 and 5 dorsal root ganglia (DRGs) of normal rats and at various intervals after unilateral sciatic nerve transection. Twenty percent of all normal DRG neurons were NPY receptor mRNA‐positive, and the majority of these neurons were of the small type, with only a few labelled medium‐sized and large neurons. In L5 normal ganglia NPY receptor mRNA colocalized with substance P, calcitonin gene‐related peptide and galanin mRNAs in small neurons, but not in medium‐sized or large neurons containing these peptides. NPY receptor mRNA was not observed in somatostatin or nitric oxide synthase mRNA‐positive neurons. Sciatic nerve transection induced a marked decrease in NPY receptor mRNA levels. However, in parallel there was a transient increase in the number of NPY receptor mRNA‐positive small neuron profiles, but the intensity of labelling was mostly very low, although a few strongly labelled, small neuron profiles were also encountered. In addition, axotomy caused a marked increase in the number of NPY receptor mRNA‐positive large neuron profiles in the ipsilateral DRGs, and they constituted 15–20% of counted DRG neuron profiles and 45–65% of counted large neuron profiles, 7–28 days after axotomy. In L5 DRGs, ipsilateral to the axotomy, NPY receptor mRNA colocalized with NPY mRNA in many large and some medium‐sized neuron profiles, with galanin mRNA in some small, medium‐sized and large neuron profiles and with vasoactive intestinal polypeptide mRNA in some small and medium‐sized neuron profiles and a few large profiles. Occasionally, NPY receptor mRNA was observed in nitric oxide synthase mRNA‐positive small neurons. In the dorsal horn, NPY receptor mRNA‐positive small neurons were concentrated in lamina II at L4 and L5 levels, and were scattered in deeper laminae. No marked changes were observed ipsilateral to the axotomy. No NPY receptor mRNA‐positive cells were found in the normal rat gracile nucleus, or in this nucleus after axotomy. These results show that a NPY receptor may be a prejunctional receptor in primary afferent neurons and play a role in the modulation of somatosensatory information, both in normal and lesioned primary afferent DRG cells. However, axotomy induced a distinct shift in NPY receptor mRNA expression from small to large neurons, indicating that sensitivity to NPY is switched from one modality to another. Thus, not only several sensory neuropeptides, as shown in previous studies, but at least also one of the peptide receptors change their expression dramatically in response to axotomy, sugges

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00246.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractWe report that kainic acid‐induced seizures lead to marked increases in mRNAs encoding basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) and fig, one of their receptors, in the rat hippocampus. Anticonvulsant pretreatment inhibits the up‐regulation of these mRNAs. The observed increase in fig mRNA levels involves the pyramidal cells of all hippocampal subfields and the granular ceils of the dentate gyrus. The increased expression of aFGF and bFGF mRNAs is limited to neuron populations that are resistant to seizure‐induced injury, the granular cells of dentate gyrus and pyramidal cells of CA1 region, respectively. The results suggest that the increase in the FGFs and fig may play pivotal roles in neuron survival and in long‐term changes occurring in the hippocampus following seizure a

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00247.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractIt is well established that the inositol lipids mediate signal transduction in several cellular populations. Many neurotransmitters, hormones and growth factors act at plasma membrane receptors to induce the hydrolysis of phosphatidylinositols and hence the generation of various inositol phosphates (IP). The best known member of this family is 1,4,5‐IP3, which is associated with the release of Ca2+from intracellular pools. It has also been proposed that two others inositides, 1,3,4,5‐IP4and IP6, may be involved in Ca2+homeostasis. In order to study the possible relevance of these various inositides in neuronal tissues, we have localized the respective receptors in rat and human brain under both acidic and basic pH conditions. In the hippocampal formation, [3H]1,3,4,5‐IP4binding sites are concentrated in the hilus and the molecular layer while a clearly different pattern of distribution is seen for [3H]1,4,5‐IP3, its highest concentration of labelling being concentrated in the oriens and radiatum laminae. This contrasting profile of distribution is also observed in other brain areas such as the caudate‐putamen, the septo‐hippocampal area, and the molecular and granular layers of the cerebellum. Moreover, while highest amounts of specific [3H]1,4,5‐IP3binding are obtained at pH 8.5, the opposite is found for [3H]1,3,4,5‐IP4, with high binding levels seen under acidic conditions. [3H]IP6binding sites are broadly distributed with specific labelling concentrated in areas enriched with neuronal perikarya such as the granular cell layer of the dentate gyrus, the pyramidal cell layers of the hippocampus and the granular cell layer of the cerebellum. [3H]IP6binding is particularly abundant at basic pH in a few regions such as the accessory olfactory bulb, the piriform cortex and the septo‐hippocampal nucleus. The pH dependency of each inositide binding may be correlated to changes in intracellular pH that are observed following the activation of phospholipase C. The apparent distribution of specific 1,4,5‐IP3, 1,3,4,5‐IP4and IP6binding sites is rather similar in rat and human brains, suggesting their preserved functions acr

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00248.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractPrevious studies have shown that following neonatal peripheral nerve injury, adjacent intact myelinated and unmyelinated primary afferents sprout into the central denervated terminal area. The present study investigates this in more detail and goes further, to study the fate of the central terminals of the surviving axotomized primary afferent neurons. Bulk labelling of the sciatic and saphenous nerves with horseradish peroxidase conjugated to choleragenoid (B‐HRP), to label the A fibres, or wheatgerm agglutinin (WGA‐HRP), to label C fibres were employed to investigate the central consequences of sciatic nerve section and ligation on the day of birth, in adult rats. Bulk labelling of the axotomized sciatic or intact saphenous nerve with either tracer and comparison with contralateral controls revealed alterations to the terminal field. The intact saphenous nerve terminal field expanded caudally from mid L4 to the L4‐L5 boundary when labelled with WGA‐HRP and to the sacral cord when labelled with B‐HRP. Labelling the axotomized sciatic nerve with either tracer revealed little change in the overall somatotopic organization of central terminals, although labelling was less intense compared to control nerves and more variable with WGA‐HRP. Invasion of the substantia gelatinosa (SG) by axotomized A fibres was observed in segments L3‐5, into the area occupied by axotomized C fibres. This area was also invaded by intact saphenous A fibres in the L4–5 segments. These results demonstrate that following neonatal nerve section: (i) axotomized primary afferents are able to retain a ‘normal’ somatotopic map in the rostrocaudal plane; (ii) both A and C fibres from adjacent intact nerves sprout into the denervated territory, but A fibres sprout further caudally; (iii) axotomized A fibres and invading intact A fibres both sprout dorsally into denervated SG. As a result, there is considerable overlap between nerve territories in denervated spinal cord, suggesting that competition for laminar termination sites exists between A and C fibres and also between axotomized and intac

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00249.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractThe development of locomotor function in the rat spans the first 3 postnatal weeks. We have studied morphological features of the soma and dendrites of motoneurons innervating the physiological flexor muscles of the ankle, tibialis anterior and extensor digitorum longus, by intracellular injectionin vitrobetween the first and ninth postnatal days. We obtained serial optical sections of 96 adequately filled motoneurons in whole‐mounted hemisected spinal cords by confocal microscopy, projected them onto a single plane and analysed them morphometrically. On the day after birth, the somatodendritic surfaces of most such motoneurons were covered in growth‐associated spiny, thorny or hair‐like appendages. These had disappeared from the soma by the fourth postnatal day and from most proximal dendrites by day 7, but were still common distally on day 9. During this period there was little or no net growth of either the soma (which was still much smaller than in the adult) or the dendritic tree. A dorsal dendritic bias was present and ‘sprays’ of long, loosely bundled dorsal dendrites were often seen. The mean number of primary dendrites remained constant at about eight, and their combined diameter was already significantly correlated with mean soma diameter, as in the adult cat. Thus, the critical neonatal period during which these ankle flexor motoneurons are known to change their electrophysiological properties and to be particularly sensitive to interference with neuromuscular interaction is characterized by major changes in the neuronal surface, presumably linked to synap

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00250.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

AbstractOxytocin binding sites were detected by autoradiography on films and emulsion‐coated sections in the spinal cord of adult and postnatal rats from C8 to L2, using a highly selective125l‐labelled oxytocin antagonist. Oxytocin binding sites were detected on all transverse sections in the dorsal horn, where labelling was scattered over laminae I and II. The autonomic areas, i.e. the intermediolateral cell column, the central grey (lamina X) and the nucleus intercalatus were labelled. Binding in the intermediolateral cell column was most frequently observed on sections from T9 to T11 in adult and T7 to T8 in postnatal rats. In this location, oxytocin binding sites were highly concentrated on cell bodies of putative sympathetic preganglionic neurons; however, not all of these cells were labelled. Diffuse labelling occurred on the dorsal part of the central grey, mainly between T8 and L2. Isolated labelled cells belonging to the nucleus intercalatus were scattered between the central canal and the intermediolateral cell column. In addition, oxytocin binding sites were found on some motoneurons of the lateral group of T12‐T13, but only in postnatal rats. The distribution of oxytocin binding sites in the rat spinal cord coincides with that of the oxytocin innervation and strongly suggests a modulatory role of this peptide in sensory and autonomic func

ISSN:0953-816X    

DOI:10.1111/j.1460-9568.1994.tb00251.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY