bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical and functional correlation of the endomorphins with mu opioid receptor splice variants
Authors: Abbadie C. , Rossi G. C. , Orciuolo A. , Zadina J. E. , Pasternak G. W. 
Published: March 2003

AbstractThe present study characterizes the relationship between the endogenous mu opioid peptides endomorphin‐1 (EM‐1) and endomorphin‐2 (EM‐2) and several splice variants of the cloned mu opioid receptor (MOR‐1) encoded by the mu opioid receptor gene (Oprm). Confocal laser microscopy revealed that fibers containing EM‐2‐like immunoreactivity (‐LI) were distributed in close apposition to fibers showing MOR‐1‐LI (exon 4‐LI) and to MOR‐1C‐LI (exons 7/8/9‐LI) in the superficial laminae of the lumbar spinal cord. We also observed colocalization of EM‐2‐LI and MOR‐1‐LI in a few fibers of lamina II, and colocalization of EM‐2‐LI and MOR‐1C‐LI in laminae I–II, and V–VI. To assess the functional relevance of the MOR‐1 variants in endomorphin analgesia, we examined the effects of antisense treatments that targeted individual exons within the Oprm1 gene on EM‐1 and EM‐2 analgesia in the tail flick test. This antisense mapping study implied mu opioid receptor mechanisms for the endomorphins are distinct from those of morphine or morphine‐6β‐glucuronide (M6G).
Differential involvement of cortical muscarinic and NMDA receptors in short‐ and long‐term taste aversion memory
Authors: Ferreira G. , Gutiérrez R. , De la Cruz V. , Bermúdez‐Rattoni F. 
Published: March 2003

AbstractIn conditioned taste aversion, an animal avoids a taste previously associated with toxic effects, and this aversive memory formation requires an intact insular cortex. In this paper, we investigated the possible differential involvement of cholinergic and glutamatergic receptors in the insular cortex in short‐term memory (STM) and long‐term memory (LTM) of taste aversion in rats. Taste aversion was induced by intraperitoneal administration of lithium chloride (a malaise‐inducing drug) 15 min after experience with an unfamiliar taste. In order to test STM and LTM of taste aversion, taste stimulus was again presented 4 h and 72 h after lithium injection, respectively. During the acquisition, microinjection of the muscarinic antagonist, scopolamine, in the insular cortex before, but not after, the presentation of the new taste, abolished STM as well as LTM. Blockade of the NMDA receptor, in the insular cortex, by AP5 before, but not after, the presentation of the taste stimulus, impaired LTM but left STM intact. Moreover, when injected 1 h after malaise induction (i.e., during taste–illness association), AP5 disrupted both STM and LTM. These results suggest that activation of muscarinic receptors in the insular cortex is involved in the acquisition of taste memory, whereas NMDA receptors participate in taste memory consolidation. These data demonstrate that different neurochemical mechanisms subserve different memory phases. NMDA receptors are also probably involved in processing the visceral input, thus allowing subsequent taste–illness association. This indicates that in the same cortical area the same neurotransmitter system can be involved in distinct processes: taste memory consolidation vs. taste–illness association.
Consequences of amygdala kindling and repeated withdrawal from ethanol on amphetamine‐induced behaviours
Authors: Ripley Tamzin L. , Dunworth Sarah J. , Stephens David N. 
Published: March 2003

AbstractIt has been shown previously that chronic ethanol treatment in mice leads to accelerated behavioural sensitization to psychomotor stimulants [Manley & Little (1997) J. Pharmacol. Exp. Ther., 281, 1330–1339], whilst repeated experience of ethanol withdrawal sensitizes pathways underlying seizure activity (Becker & Hale (1993) Alcohol Clin. Exp. Res., 17, 94–98]. The aim of the current experiment was to investigate the consequences of repeated withdrawal from ethanol on amphetamine‐induced behaviours in the rat and compare this with animals with electrical kindling of the amygdala, a procedure that has been shown to enhance alcohol withdrawal seizures [Pinel et al. (1975) Can. J. Neurol. Sci., 2, 467–475]. For the kindling experiments, electrodes were surgically implanted in the left basolateral amygdala and were stimulated daily at the afterdischarge threshold until a criterion of three consecutive stage 5 seizures was reached. Fully kindled rats showed a marginally significant reduction in sensitivity to the locomotor stimulant effects of acute amphetamine compared with sham and partially kindled rats which had experienced subthreshold stimulation of the amygdala. Sham and partially kindled rats sensitized readily to the locomotor activating effects of amphetamine (0.125 mg/kg) following repeated treatments, but the fully kindled rats did not. Fully kindled rats also failed to show place preference conditioning to amphetamine (0.5 mg/kg). Rats, withdrawn three times from chronic ethanol (liquid‐diet), kindled more quickly to PTZ (30 mg/kg, i.p.) than rats with the same overall exposure to ethanol (24 days) followed by a single withdrawal or control animals. However, there was no difference in the locomotor stimulating effects of acute amphetamine (0.25–1 mg/kg, i.p.), the rate of sensitization to amphetamine (0.125 mg/kg, i.p.) or amphetamine induced conditioned place preference (1 mg/kg, i.p.). These observations suggest that, in rats, repeated withdrawal from a relatively mild chronic ethanol treatment modulates neuronal systems that may also be involved in PTZ‐induced kindling but not those involved in either the acute stimulant effects of amphetamine or behavioural sensitization or appetitive conditioning following repeated amphetamine administration. Behavioural changes following amygdala kindling differed from those following repeated ethanol withdrawal, suggesting that withdrawal kindling from a mild ethanol treatment differs in its effects from amygdala kindling.
In the rat, exogenous melatonin increases the amplitude of pineal melatonin secretion by a direct action on the circadian clock
Authors: Bothorel Béatrice , Barassin Stéphane , Saboureau Michel , Perreau Stéphanie , Vivien‐Roels Berthe , Malan André , Pévet Paul 
Published: March 2003

AbstractThe effect of exogenous melatonin on pineal melatonin synthesis was studied in the rat in vivo. Daily melatonin profiles were measured by transpineal microdialysis over 4 consecutive days in rats maintained on a 12‐h light : 12‐h dark schedule (LD 12 : 12). Curve‐fitting was used to determine the amplitude of the peak of melatonin production, and the times of its onset (IT50) and offset (DT50). A subcutaneous injection of melatonin (1 mg/kg) at the onset of darkness (ZT12) induced an advance of IT50 on the second day after the treatment, in 50% of the animals kept in LD. When the animals were switched to constant darkness, the treatment caused no detectable advance of IT50, while 70% of individuals showed a significant delay in DT50 2 days after the injection. Locally infusing the drug by reverse microdialysis into the suprachiasmatic nuclei (SCN) failed to enhance the shift in melatonin onset. Following subcutaneous melatonin injection, a significant increase (≈ 100%) in melatonin peak amplitude was observed. This increase persisted over 2 days and occurred only when the melatonin was applied at ZT12, but not at ZT6, 17 or 22. The effect was also observed when the drug was infused directly into the SCN, but not into the pineal. Thus, the SCN are the target site for the effect of exogenous melatonin on the amplitude of the endogenous melatonin rhythm, with a similar window of sensitivity as its phase‐shifting effect on the pacemaker.
Passive avoidance training enhances cell proliferation in 1‐day‐old chicks
Authors: Dermon C. R. , Zikopoulos B. , Panagis L. , Harrison E. , Lancashire C. L. , Mileusnic R. , Stewart M. G. 
Published: March 2003

AbstractOne‐day‐old domestic chicks were injected i.p. with bromodeoxyuridine (BrdU) before training on a one‐trial passive avoidance task where the aversive experience was a bead coated with a bitter tasting substance, methyl anthranilate (MeA). Animals were tested 24 h later; those avoiding (if MeA‐trained) or pecking if water (W)‐trained (which they peck appetitively), along with a group of untrained naïve chicks, were used to determine cell proliferation either 24 h or 9 days post BrdU injection. In all three groups, BrdU positive cells were identified sparsely throughout the forebrain but labelling was pronounced around ventricular zone (VZ) surfaces at both 24 h and 9 days post‐BrdU‐injection. Double immunolabelling with neuronal specific antibodies, to either NeuN, or β‐tubulin III, confirmed that most BrdU labelled cells appeared to be neurons. Unbiased stereological analysis of labelled cells in selected forebrain areas 24 h post BrdU injection showed a significant MeA‐training induced increase in labelled cells in both the dorsal VZ surface bordering the intermediate and medial hyperstriatum ventrale (IMHV) and the tuberculum olfactorium (TO). By 9 days post‐BrdU‐injection, there was a significantly greater number of BrdU labelled cells in MeA‐trained birds within the IMHV, lobus parolfactorius (LPO) and TO. These results demonstrate that avoidance training in 1‐day‐old chicks has a marked effect on cell proliferation, in the LPO and IMHV, regions of the chick previously identified as a key loci of memory formation, and in a second region (TO), which has olfactory functions, but has not been previously investigated in relation to avoidance learning.
Postnatal innervation of the rat superior colliculus by axons of late‐born retinal ganglion cells
Authors: Dallimore Elizabeth J. , Cui Qi , Beazley Lyn D. , Harvey Alan R. 
Published: March 2003

AbstractRat retinal ganglion cells (RGCs) are generated between embryonic day (E) 13 and E19. Retinal axons first reach the superior colliculus at E16/16.5 but the time of arrival of axons from late‐born RGCs is unknown. This study examined (i) whether there is a correlation between RGC genesis and the timing of retinotectal innervation and (ii) when axons of late‐born RGCs reach the superior colliculus. Pregnant Wistar rats were injected intraperitoneally with bromodeoxyuridine (BrdU) on E16, E18 or E19. Pups from these litters received unilateral superior colliculus injections of fluorogold (FG) at ages between postnatal (P) day P0 and P6, and were perfused 1–2 days later. RGCs in 3 rats from each BrdU litter were labelled in adulthood by placing FG onto transected optic nerve. Retinas were cryosectioned and the number of FG, BrdU and double‐labelled (FG+/BrdU+) RGCs quantified. In the E16 group, the proportion of FG‐labelled RGCs that were BrdU+ did not vary with age, indicating that axons from these cells had reached the superior colliculus by P0/P1. In contrast, for the smaller cohorts of RGCs born on E18 or E19, the proportion of BrdU+ cells that were FG+ increased significantly after birth; axons from most RGCs born on E19 were not retrogradely FG‐labelled until P4/P5. Thus there is a correlation between birthdate and innervation in rat retinotectal pathways. Furthermore, compared to the earliest born RGCs, axons from late‐born RGCs take about three times longer to reach the superior colliculus. Later‐arriving axons presumably encounter comparatively different growth terrains en route and eventually innervate more differentiated target structures.
Identification and comparative analysis of differentially expressed proteins in rat striatum following 6‐hydroxydopamine lesions of the nigrostriatal pathway: up‐regulation of amyloid precursor‐like protein 2 expression
Authors: Shen Yan , Yu Yi , Guo Hong , Tang Zhongshu , Yu Fu‐Shin X. , Zhou Jiawei 
Published: March 2003

AbstractDuring neurodegenerative processes, cascades of degeneration and subsequent regeneration are triggered. However, the molecular nature of the factors involved in the neurodegeneration of the CNS remains largely unknown. In this study, the variations of protein expression in the striatum of adult Sprague–Dawley rats following 6‐hydroxydopamine lesions were investigated, in order to better understand the molecular events occurring in the denervated target tissue. The rat striatum, ipsilateral to the lesion was analysed by two‐dimensional gel electrophoresis followed by matrix assisted laser desorption/ionization‐time of flight mass spectrometry. Seven proteins were up‐regulated (188.1–750% compared to control) in response to the lesion: amyloid precursor‐like protein 2 (APLP2), kininogen, glucokinase, tropomyosin α chain, type brain‐1 and calpactin I light chain; whilst four proteins, neural epidermal growth factor‐like 2, minichromosome maintenance 6, and thyroid hormone receptor β‐2, were down‐regulated (to between 36% and 59% of levels in sham‐operated controls). Three proteins that did not match with available data in the SWISS‐PROT protein database were also determined. Immunohistochemical analysis demonstrated colocalization of APLP2 and tyrosine hydroxylase in the nigral neurons. Moreover, reduction of APLP2‐positive neurons in the substantia nigra pars compacta as well as the increases in the substantia nigra pars reticulata and in the striatum were observed. Furthermore, the conditioned medium of the Chinese hamster ovary cells over‐expressing APLP2‐751 (chondroitin sulphate‐modified), but not APLP2‐763 (nonchondroitin sulphate‐modified), was able to increase the number of the tyrosine hydroxylase‐positive neurons in fetal mesencephalic cultures. These results suggest that the expression of APLP2, a protein that has been thought to be associated with Alzheimer's disease, is up‐regulated in the striatum following dopaminergic denervation. They also support the view that chondroitin sulphate‐modified APLP2 protein may play an important role in the dopaminergic nigrostriatal system.
Zinc‐induced inhibition of protein synthesis and reduction of connexin‐43 expression and intercellular communication in mouse cortical astrocytes
Authors: Alirezaei Mehrdad , Mordelet Elodie , Rouach Nathalie , Nairn Angus C. , Glowinski Jacques , Prémont Joël 
Published: March 2003

AbstractZinc released from a subpopulation of glutamatergic synapses, mainly localized in the cerebral cortex and the hippocampus, facilitates or reduces glutamatergic transmission by acting on neuronal AMPA and NMDA receptors, respectively. However, neurons are not the only targets of zinc. In the present study, we provide evidence that zinc inhibits protein synthesis in cultured astrocytes from the cerebral cortex of embryonic mice. This inhibition, which reached 85% in the presence of 100 µm zinc, was partially and slowly reversible and resulted from the successive inhibition of the elongation and the initiation steps of the protein translation process. This was assessed by measuring the phosphorylation level of the elongation factor eEF‐2 and of the α subunit of the initiation factor eIF‐2. Due to the rapid turnover of connexin‐43 that forms junction channels in cultured astrocytes, the zinc‐induced decrease of protein synthesis led to a partial disappearance of connexin‐43, which was associated with an inhibition of the cellular coupling in the astrocytic syncitium. In conclusion, zinc not only inhibits protein synthesis in neurons, as previously demonstrated, but also in astrocytes. The resulting decrease in the intercellular communication between astrocytes should alter the function of surrounding neurons as well as their survival.
In vivo infusions of exogenous growth factors into the fourth ventricle of the adult mouse brain increase the proliferation of neural progenitors around the fourth ventricle and the central canal of the spinal cord
Authors: Martens David J. , Seaberg Raewyn M. , Van Der Kooy Derek 
Published: March 2003

AbstractStem cells isolated from the fourth ventricle and spinal cord form neurospheres in vitro in response to basic fibroblast growth factor (FGF2)+heparin (H) or epidermal growth factor (EGF)+FGF2 together. To determine whether these growth factor conditions are sufficient to induce stem cells within the fourth ventricle and spinal cord to proliferate and expand their progeny in vivo, we infused EGF and FGF2, alone or together, with or without H, into the fourth ventricle for 6 days via osmotic minipumps. Animals were injected with bromodeoxyuridine (BrdU) on days 4, 5 and 6 of infusion in order to label cells proliferating in response to the growth factors. Infusions of EGF+FGF2+H into the fourth ventricle resulted in the largest proliferative effect, a 10.8‐fold increase in the number of BrdU+ cells around the fourth ventricle, and a 33.5‐fold increase in the number of BrdU+ cells around the central canal of the spinal cord, as compared to vehicle infused controls. The majority of the cells were nestin+ after 6 days of infusion. Seven weeks post‐infusion, 22 and 30% of the number of BrdU+ cells induced to proliferate after 6 days of EGF+FGF2+H infusions were still detected around the fourth ventricle and central canal of the spinal cord, respectively. Analysis of the fates of the remaining cells showed that a small percentage of BrdU+ cells around the fourth ventricle and in the white matter of the spinal cord differentiated into astrocytes and oligodendrocytes. BrdU+ neurons were not found in the brainstem or in the grey matter of the cervical spinal cord 7 weeks post‐infusion. These results show that endogenous stem cells and progenitors around the fourth ventricle and central canal of the spinal cord proliferate in response to exogenously applied growth factors, but unlike in the lateral ventricle where they generate some new neurons, they only produce new astrocytes and oligodendrocytes at 7 weeks post‐infusion.
The cerebellum in action: a simulation and robotics study
Authors: Hofstötter Constanze , Mintz Matti , Verschure Paul F. M. J. 
Published: March 2003

AbstractThe control or prediction of the precise timing of events are central aspects of the many tasks assigned to the cerebellum. Despite much detailed knowledge of its physiology and anatomy, it remains unclear how the cerebellar circuitry can achieve such an adaptive timing function. We present a computational model pursuing this question for one extensively studied type of cerebellar‐mediated learning: the classical conditioning of discrete motor responses. This model combines multiple current assumptions on the function of the cerebellar circuitry and was used to investigate whether plasticity in the cerebellar cortex alone can mediate adaptive conditioned response timing. In particular, we studied the effect of changes in the strength of the synapses formed between parallel fibres and Purkinje cells under the control of a negative feedback loop formed between inferior olive, cerebellar cortex and cerebellar deep nuclei. The learning performance of the model was evaluated at the circuit level in simulated conditioning experiments as well as at the behavioural level using a mobile robot. We demonstrate that the model supports adaptively timed responses under real‐world conditions. Thus, in contrast to many other models that have focused on cerebellar‐mediated conditioning, we investigated whether and how the suggested underlying mechanisms could give rise to behavioural phenomena.
TRKB signalling controls the expression of N‐methyl‐d‐aspartate receptors in the visual cortex
Authors: Margotti Elisa , Covaceuszach Sonia , Tongiorgi Enrico , Cattaneo Antonino , Domenici Luciano 
Published: March 2003

AbstractNMDA receptors (NMDARs) are multimeric proteins, the biological and functional characteristics of which depend on differential subunit assembly during postnatal development. In the present paper, we investigated whether the expression of NMDAR subunits NR1, NR2A, NR2B is influenced by neurotrophins in rat visual cortex. We used a soluble form of the TrkB receptor engineered as an immunoadhesin (TrkB‐IgG) in order to block TrkB ligands. TrkB‐IgG was released through a cannula implanted in the occipital pole and connected to a mini‐osmotic pump. TrkB‐IgG was continuously released from postnatal day 20–21 (P20–21) to P36–37. In a different group of animals used as controls, osmotic pumps were filled with saline. Different antibodies were used to stain neurons expressing NR1, NR2A and NR2B. We counted the number of neurons stained for NR2A and NR2B subunits and expressed this as percentage with respect to the total number of cresyl‐violet stained neurons in each cortical layer. In the visual cortex of TrkB‐IgG‐treated rats, the percentage of neurons expressing NR2A was significantly increased in all cortical layers. Concerning the NR2B subunit, the percentage of stained neurons was not significantly different between TrkB‐IgG‐treated and control rats. The staining level for both NR2A and NR2B, but not NR1, was reduced in all cortical layers in TrkB‐IgG‐treated animals. In agreement with this result, the endogenous levels of NR2A and NR2B subunits were reduced in TrkB‐IgG‐treated animals as shown by Western blotting. Thus, TrkB signalling controls the cellular expression of NMDAR subunits in visual cortical neurons during postnatal development.
Evidence for a direct projection from the paraventricular nucleus of the hypothalamus to putative serotoninergic neurons of the nucleus paragigantocellularis involved in the control of erection in rats
Authors: Bancila M. , Giuliano F. , Rampin O. , Mailly P. , Brisorgueil M.‐J. , Calas A. , Vergé D. 
Published: March 2003

AbstractIn the male rat, serotoninergic neurons of the ventrolateral medulla send direct projections onto spinal preganglionic neurons that innervate the penis. The role of the paraventricular nucleus of the hypothalamus in the control of penile erection is well recognized. Our aim was to demonstrate anatomical relation between paraventricular neurons and medullary serotoninergic neurons innervating the penis. In adult male rats, stereotaxic iontophoretic injections of Phaseolus vulgaris leuco‐agglutinin were performed in the paraventricular nucleus. Neurons in the ventrolateral medulla were retrogradely labelled using transneuronal retrograde transport of pseudorabies virus injected in the corpus cavernosum. Sections of the ventro‐lateral medulla were processed for double immunofluorescence to reveal both Phaseolus vulgaris leuco‐agglutinin and pseudorabies virus using specific antibodies. Sections were also processed for the simultaneous detection of pseudorabies virus and serotonin. Pseudorabies virus‐infected neurons in the ventrolateral medulla were present in the nucleus paragigantocellularis, reticular formation of the medulla, raphe pallidus and raphe magnus. In the nucleus paragigantocellularis, all pseudorabies virus‐infected‐neurons were immunoreactive for serotonin. Some of them received Phaseolus vulgaris leuco‐agglutinin‐labelled varicose fibres that ran along the soma of pseudorabies virus‐infected neurons. Confocal microscopy suggested the presence of several close appositions between them, which were demonstrated using three‐dimensional reconstruction of serial optical sections. Our results show that paraventricular neurons send direct projections in the nucleus paragigantocellularis onto neurons that innervate the penis. They suggest a possible role of the paraventricular nucleus in penile erection through the control of descending serotoninergic raphe‐spinal neurons. The neurotransmitter used in this pathway remains to be determined.