bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sexual dimorphism in the spontaneous recovery from spinal cord injury: a gender gap in beneficial autoimmunity?
Authors: Hauben Ehud , Mizrahi Tal , Agranov Evgenia , Schwartz Michal 
Published: March 2003

AbstractImmune cells have been shown to contribute to spontaneous recovery from central nervous system (CNS) injury. Here we show that adult female rats and mice recover significantly better than their male littermates from incomplete spinal cord injury (ISCI). This sexual dimorphism is wiped out and recovery is worse in adult mice deprived of mature T cells. After spinal cord contusion in adult rats, functional recovery (measured by locomotor scores in an open field) was significantly worse in females treated with dihydrotestosterone prior to the injury than in placebo‐treated controls, and significantly better in castrated males than in their noncastrated male littermates. Post‐traumatic administration of the testosterone receptor antagonist flutamide promoted the functional recovery in adult male rats. These results, in line with the known inhibitory effect of testosterone on cell‐mediated immunity, suggest that androgen‐mediated immunosuppression plays a role in ISCI‐related immune dysfunction and can therefore partly explain the worse outcome of ISCI in males than in female. We suggest that females, which are more prone to develop autoimmune response than males, benefit from this response in cases of CNS insults.
Characterization of a novel NCAM ligand with a stimulatory effect on neurite outgrowth identified by screening a combinatorial peptide library
Authors: Rønn Lars C. B. , Olsen Marianne , Soroka Vladislav , Østergaard Søren , Dissing Steen , Poulsen Flemming M. , Holm Arne , Berezin Vladimir , Bock Elisabeth 
Published: March 2003

AbstractThe neural cell adhesion molecule, NCAM, plays a key role in neural development and plasticity mediating cell adhesion and signal transduction. By screening a combinatorial library of synthetic peptides with NCAM purified from postnatal day 10 rat brains, we identified a nonapeptide, termed NCAM binding peptide 10 (NBP10) and showed by nuclear magnetic resonance analysis that it bound the NCAM IgI module of NCAM. NBP10 modulated cell aggregation as well as neurite outgrowth induced specifically by homophilic NCAM binding. Moreover, both monomeric and multimeric forms of NBP10 stimulated neurite outgrowth from primary hippocampal neurons. The neurite outgrowth response to NBP10 was inhibited by a number of compounds previously shown to inhibit neurite outgrowth induced by homophilic NCAM binding, including voltage‐dependent calcium channel antagonists, suggesting that NBP10 induced neurite outgrowth by activating a signal transduction pathway similar to that activated by NCAM itself. Moreover, an inhibitor of intracellular calcium mobilization, TMB‐8, prevented NBP10‐induced neurite outgrowth suggesting that NCAM‐dependent neurite outgrowth also requires mobilization of calcium from intracellular calcium stores in addition to calcium influx from extracellular sources. By single‐cell calcium imaging we further demonstrated that NBP10 was capable of inducing an increase in intracellular calcium in PC12E2 cells. Thus, the NBP10 peptide is a new tool for the study of molecular mechanisms underlying NCAM‐dependent signal transduction and neurite outgrowth, and could prove to be a useful modulator of regenerative processes in the peripheral and central nervous system.
Reorganization of descending motor tracts in the rat spinal cord
Authors: Raineteau Olivier , Fouad Karim , Bareyre Florence M. , Schwab Martin E. 
Published: March 2003

AbstractFollowing lesion of the central nervous system (CNS), reinnervation of denervated areas may occur via two distinct processes: regeneration of the lesioned fibres or/and sprouting from adjacent intact fibres into the deafferented zone. Both regeneration and axonal sprouting are very limited in the fully mature CNS of higher vertebrates, but can be enhanced by neutralizing the neurite outgrowth inhibitory protein Nogo‐A. This study takes advantage of the distinct spinal projection pattern of two descending tracts, the corticospinal tract (CST) and the rubrospinal tract (RST), to investigate if re‐innervation of denervated targets can occur by sprouting of anatomically separate, undamaged tracts in the adult rat spinal cord. The CST was transected bilaterally at its entry into the pyramidal decussation. Anatomical studies of the RST in IN‐1 antibody‐treated rats showed a reorganization of the RST projection pattern after neutralization of the myelin associated neurite growth inhibitor Nogo‐A. The terminal arborizations of the rubrospinal fibres, which are normally restricted to the intermediate layers of the spinal cord, invaded the ventral horn but not the dorsal horn of the cervical spinal cord. Moreover, new close appositions were observed, in the ventral horn, onto motoneurons normally receiving CST projections. Red nucleus microstimulation experiments confirmed the reorganization of the RST system. These observations indicate that mature descending motor tracts are capable of significant intraspinal reorganization following lesion and suggests the expression of cues guiding and/or stabilizing newly formed sprouts in the adult, denervated spinal cord.
Overexpression of corticotropin‐releasing hormone in transgenic mice and chronic stress‐like autonomic and physiological alterations
Authors: Dirks Anneloes , Groenink Lucianne , Bouwknecht J. Adriaan , Hijzen Theo H. , Van Der Gugten Jan , Ronken Eric , Verbeek J. Sjef , Veening Jan G. , Dederen Pieter J. W. C. , Korosi Aniko , Schoolderman Louise F. , Roubos Eric W. , Olivier Berend 
Published: March 2003

AbstractTo gain a greater insight into the relationship between hyperactivity of the corticotropin‐releasing hormone (CRH) system and autonomic and physiological changes associated with chronic stress, we developed a transgenic mouse model of central CRH overproduction. The extent of central and peripheral CRH overexpression, and the amount of bioactive CRH in the hypothalamus were determined in two lines of CRH‐overexpressing (CRH‐OE) mice. Furthermore, 24 h patterns of body temperature, heart rate, and activity were assessed using radiotelemetry, as well as cumulative water and food consumption and body weight gain over a 7‐day period. CRH‐OE mice showed increased amounts of CRH peptide and mRNA only in the central nervous system. Despite the presence of the same CRH transgene in their genome, only in one of the two established lines of CRH‐OE mice (line 2122, but not 2123) was overexpression of CRH associated with increased levels of bioactive CRH in the hypothalamus, increased body temperature and heart rate (predominantly during the light (inactive) phase of the diurnal cycle), decreased heart rate variability during the dark (active) phase, and increased food and water consumption, when compared with littermate wildtype mice. Because line 2122 of the CRH transgenic mice showed chronic stress‐like neuroendocrine and autonomic changes, these mice appear to represent a valid animal model for chronic stress and might be valuable in the research on the consequences of CRH excess in situations of chronic stress.
Retinofugal projections following early lesions of the visual cortex in the ferret
Authors: Restrepo C. Ernesto , Manger Paul R. , Innocenti Giorgio M. 
Published: March 2003

AbstractExtensive lesions of the occipital cortex comprising the developing occipital visual areas and beyond in young ferrets (postnatal day 5) are followed by massive, but incomplete, degeneration of the lateral geniculate (LGN) and lateralis posterior (LP) nuclei of the thalamus, and minor volumetric reduction of the superior colliculus. Retinal projections (revealed by intraocular tracer injections), while reduced, remain confined to their territories of normal termination, both in the adult and throughout development. Comparisons with other mammalian species point to several common features in the developmental plasticity of retinofugal pathway.
Cellular imaging with zif268 expression in the rat nucleus accumbens and frontal cortex further dissociates the neural pathways activated following the retrieval of contextual and cued fear memory
Authors: Thomas Kerrie L. , Hall Jeremy , Everitt Barry J. 
Published: March 2003

AbstractQuantitative in situ hybridization revealed that the expression of the plasticity‐associated gene zif268 was increased in specific regions of the rat frontal cortex and nucleus accumbens following fear memory retrieval. Increased expression of zif268 was observed in neurons in the core of the nucleus accumbens during the retrieval of contextual and discrete cued fear associations. In contrast, zif268 expression was additionally induced in neurons of the nucleus accumbens shell and the anterior cingulate cortex during the retrieval of contextual but not cued fear memories. No changes in the expression of this gene were seen in the ventral medial prefrontal cortex or ventral and lateral regions of the orbitofrontal cortex that were correlated specifically with the retrieval of fear memory. These experiments demonstrate the specific and dissociable activation of limbic cortical–ventral striatal regions that accompanies cued and contextual fear. These data, together with those previously published by our laboratory (Hall, J., Thomas, K.L. & Everitt, B.J. (2001) J. Neurosci., 21, 2186–2193), suggest that retrieval of contextual fear memories activates a wider limbic cortical–ventral striatal neural circuitry than does retrieval of cued fear memories. Moreover, the expression of zif268 may contribute to plasticity and reconsolidation of fear memory in these dissociable pathways.
EphB receptors influence growth of ephrin‐B1‐positive statoacoustic nerve fibers
Authors: Bianchi Lynne M. , Gray Neil A. 
Published: March 2003

AbstractThe Eph family of receptors and ligands has been implicated in a variety of developmental processes, including the provision of inhibitory guidance cues to developing nerve fibers. A unique property of the B class of receptors is that they are able to phosphorylate ephrin‐B ligands, allowing for bi‐directional, or reverse signalling. While most of the studies to date have focused on central nerve fibers, little is known about the role of Eph molecules in guiding nerve fibers of the peripheral nervous system. In the present study, ephrin‐B1 was found to be highly expressed on developing peripheral nerve fibers including auditory and vestibular (statoacoustic) and dorsal root ganglion nerve fibers. In vitro assays revealed that EphB‐Fc receptors inhibited further growth of statoacoustic nerve fibers. In contrast, EphA7‐Fc and ephrin‐B2‐Fc did not prevent further growth of SAG. Together, these results suggest a role for EphB receptors in providing guidance signals to ephrin‐B1‐positive SAG nerve fibers.
Conditioned appetitive stimulus increases extracellular dopamine in the nucleus accumbens of the rat
Authors: Datla K. P. , Ahier R. G. , Young A. M. J. , Gray J. A. , Joseph M. H. 
Published: March 2003

AbstractThis study used in vivo microdialysis to examine the release of dopamine (DA) in the nucleus accumbens (nAc) during the performance of a previously learned, signalled sucrose reward task, and during conditioning of a neutral tone stimulus to this reward. Behavioural measures (magazine entries) confirmed that stimuli associated with sucrose presentation became secondary rewarding stimuli, and DA release was also monitored during subsequent presentation of these stimuli alone. Perhaps surprisingly, during magazine entry for consumption of sucrose, i.e. in conditions similar to routine training, dialysate DA levels in the nAc did not increase. In contrast, during conditioning of the tone with light‐sucrose, dopamine levels increased consistently and significantly. Interestingly, DA levels were somewhat, but significantly, increased when tone alone was presented in a test session, i.e. two hours after conditioning, and even more so when tone was combined with the light previously associated with sucrose. In this latter case the number of magazine entries increased to a level similar to that seen during conditioning. Presentation of light alone resulted in a similar level of magazine entries to tone alone, but no significant increase in DA. In summary, these studies confirm that a neutral stimulus can acquire the behavioural properties of reward when conditioned. The neurochemical data, on the other hand, suggest that increases of DA in nAc are more likely to be related to new associative learning than to established incentive or consumatory processes. The increase in DA release in the test session may be related either to the secondary reinforcing properties acquired by the stimulus, or to the change in contingencies, or to the aversive effects of the omission of reward.
Plantar flexor stretch reflex responses to whole body loading/unloading during human walking
Authors: Grey Michael J. , Van Doornik Johan , Sinkjær Thomas 
Published: March 2003

AbstractNumerous animal and human studies have shown that afferent information from the periphery contributes to the control of walking. In particular, recent studies have consistently shown that load receptor input is an important element of the locomotion control mechanism. The objective of this study was to investigate the contribution of load receptor feedback to the compensatory stretch reflex response. We examined the contribution of load receptor feedback to the magnitude of the short and medium latency components of the ankle plantar flexor stretch reflex responses following an unexpected dorsiflexion perturbation during human walking. Three body load conditions were investigated: normal body load, a 30% increase in body load, and a 30% decrease in body load. Healthy subjects walked on a treadmill at ∼ 3.6 km/h with the left ankle attached to a portable stretching device. Dorsiflexion perturbations (8°; 350–425 °/s) were generated during the late stance phase of gate (∼ 400 ms following heel contact). Electromyographic activity was recorded from the soleus, tibialis anterior, medial gastrocnemius, rectus femoris, and biceps femoris muscles using bipolar surface electrodes. Stretch reflex responses were observed in the soleus and gastrocnemius muscles for all of the body load conditions; however, increasing or decreasing the body load did not affect the timing and magnitude of the responses. This study provides evidence that load receptor input does not contribute strongly to the corrective response of the stretch reflex in the plantar flexor muscles during walking.
Interaction of linear vestibular and visual stimulation in the macaque ventral intraparietal area (VIP)
Authors: Schlack Anja , Hoffmann Klaus‐Peter , Bremmer Frank 
Published: March 2003

AbstractNavigation in space requires the brain to combine information arising from different sensory modalities with the appropriate motor commands. Sensory information about self‐motion in particular is provided by the visual and the vestibular system. The macaque ventral intraparietal area (VIP) has recently been shown to be involved in the processing of self‐motion information provided by optical flow, to contain multimodal neurons and to receive input from areas involved in the analysis of vestibular information. By studying responses to linear vestibular, visual and bimodal stimulation we aimed at gaining more insight into the mechanisms involved in multimodal integration and self‐motion processing. A large proportion of cells (77%) revealed a significant response to passive linear translation of the monkey. Of these cells, 59% encoded information about the direction of self‐motion. The phase relationship between vestibular stimulation and neuronal responses covered a broad spectrum, demonstrating the complexity of the spatio‐temporal pattern of vestibular information encoded by neurons in area VIP. For 53% of the direction‐selective neurons the preferred directions for stimuli of both modalities were the same; they were opposite for the remaining 47% of the neurons. During bimodal stimulation the responses of neurons with opposite direction selectivity in the two modalities were determined either by the visual (53%) or the vestibular (47%) modality. These heterogeneous responses to unimodal and bimodal stimulation might be used to prevent misjudgements about self‐ and/or object‐motion, which could be caused by relying on information of one sensory modality alone.
Time‐dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study
Authors: Nyffeler Thomas , Pierrot‐Deseilligny Charles , Felblinger Jaques , Mosimann Urs P. , Hess Christian W. , Müri René M. 
Published: March 2003

AbstractThe performance of memory‐guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double‐pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory‐guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long‐delay paradigm.    These results suggest a time‐dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC‐independent component.
ATP and UTP excite sensory neurons and induce CREB phosphorylation through the metabotropic receptor, P2Y2
Authors: Molliver Derek C. , Cook Sean P. , Carlsten Julie A. , Wright Douglas E. , McCleskey Edwin W. 
Published: March 2003

AbstractExtracellular ATP rapidly excites nociceptive sensory neurons by opening ATP‐gated ion channels (P2X receptors). Here, we describe two actions of both ATP and UTP on rat sensory neurons that are relatively slow and sustained: phosphorylation of the transcription factor CREB and delayed action potential firing that persists for tens of seconds after removal of the ligand. The pharmacology of these responses indicates that they are mediated by the metabotropic receptor P2Y2, and not by P2X receptors. CREB phosphorylation occurred in a subset of small peripherin‐positive neurons likely to be unmyelinated nociceptors. In situ hybridization analysis revealed widespread expression of P2Y2 mRNA in sensory neurons. CREB phosphorylation is mediated by both action‐potential‐evoked calcium influx and calcium release from intracellular stores. These findings suggest that P2Y2 contributes to the transduction of ATP‐mediated sensory signalling, and may be involved in the activity‐dependent regulation of nociceptor phenotype.
5,7‐dihydroxytryptamine lesions enhance and serotonergic grafts normalize the evoked overflow of acetylcholine in rat hippocampal slices
Authors: Birthelmer Anja , Schweizer Theresa , Jeltsch Hélène , Jackisch Rolf , Cassel Jean‐Christophe 
Published: March 2003

AbstractAdult rats were subjected to intracerebroventricular injections of 5,7‐dihydroxytryptamine (5,7‐DHT; 150 µg) and, 15 days later, to intrahippocampal grafts of fetal raphe cell suspensions. About 11 months later, we assessed baseline and electrically evoked release of tritium ([3H]) in hippocampal slices, preloaded with tritiated ([3H])choline or [3H]serotonin (5‐HT), in the presence or absence of the 5‐HT1B receptor agonist CP‐93,129 and the 5‐HT receptor antagonist methiothepine. HPLC determinations of monoamine concentrations were also performed. The lesions reduced the concentration of 5‐HT (−90%) and the accumulation (−80%) as well as the evoked release (−90%) of [3H]5‐HT. They also decreased the inhibitory effects of CP‐93,129 on the evoked release of [3H]5‐HT. Most interestingly, they facilitated the evoked release of [3H]acetylcholine (+20%). In slices from rats subjected to lesions and grafts, the responsiveness of the serotonergic autoreceptors (presumably located on the terminals of the grafted neurons) and the release of acetylcholine were close to normal. These results confirm that grafts rich in serotonergic neurons may partially compensate for the dramatic effects of 5,7‐DHT lesions on serotonergic hippocampal functions. The lesion‐induced reduction of the 5‐HT1B autoreceptor‐mediated inhibition of evoked 5‐HT release may be an adaptation enhancing serotonergic transmission in the (few) remaining terminals. The facilitated release of acetylcholine is probably caused by a reduced serotonergic tone on the inhibitory 5‐HT1B heteroreceptors of the cholinergic terminals. When related to data in the literature, this facilitation may be of particular interest in terms of transmitter‐based strategies developed to tackle cognitive symptoms related to neurodegenerative diseases.
Genetic engineering of mouse embryonic stem cells by Nurr1 enhances differentiation and maturation into dopaminergic neurons
Authors: Chung Sangmi , Sonntag Kai‐C. , Andersson Therese , Bjorklund Lars M. , Park Jae‐Joon , Kim Dong‐Wook , Kang Un Jung , Isacson Ole , Kim Kwang‐Soo 
Published: March 2003

AbstractNurr1 is a transcription factor critical for the development of midbrain dopaminergic (DA) neurons. This study modified mouse embryonic stem (ES) cells to constitutively express Nurr1 under the elongation factor‐1α promoter. The Nurr1‐expression in ES cells lead to up‐regulation of all DA neuronal markers tested, resulting in about a 4‐ to 5‐fold increase in the proportion of DA neurons. In contrast, other neuronal and glial markers were not significantly changed by Nurr1 expression. It was also observed that there was an additional 4‐fold increase in the number of DA neurons in Nurr1‐expressing clones following treatment with Shh, FGF8 and ascorbic acid. Several lines of evidence suggest that these neurons may represent midbrain DA neuronal phenotypes; firstly, they coexpress midbrain DA markers such as aromatic l‐amino acid decarboxylase, calretinin, and dopamine transporter, in addition to tyrosine hydroxylase and secondly, they do not coexpress other neurotransmitters such as GABA or serotonin. Finally, consistent with an increased number of DA neurons, the Nurr1 transduction enhanced the ability of these neurons to produce and release DA in response to membrane depolarization. This study demonstrates an efficient genetic manipulation of ES cells that facilitates differentiation to midbrain DA neurons, and it will serve as a framework of genetic engineering of ES cells by key transcription factor to regulate their cell fate.