bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of corticospinal tract regeneration in the chronically injured spinal cord
Authors: Ferguson Ian A. , Koide Tomoaki , Rush. Robert A. 
Published: March 2003

AbstractAcute spinal cord injury models have proved popular in studies aimed at identifying factors capable of influencing axonal regeneration within the central nervous system. In these models, the test factors (e.g. graft tissues or cells, antibodies, growth factors, etc.) are typically administered at the time of spinal cord injury. In this study, we use a rat chronic spinal cord injury model to identify possible factors which can stimulate regeneration of the chronically lesioned corticospinal tract axons. We demonstrate that surgical grafting of segments of autologous, preligated sural nerve, into the syrinx, stimulates sprouting and regeneration of the corticospinal tract as evidenced by the presence of anterograde labelled corticospinal tract processes within the cavity walls two or more weeks after treatment. Regrowing corticospinal processes were not observed within control animals. The anterogradely labelled corticospinal tract axons were found exclusively within the central grey tissue comprising the cavity walls with no regrowing corticospinal process observed within the white matter. A similar pattern of regeneration was observed following injection into the cavity of a suspension of minced autologous preligated sural nerve. Evidence of corticospinal tract regeneration was seen when either wheat germ agglutinin–horseradish peroxidase or biotinylated–dextran was used as an anterograde tracer. These data demonstrate that the chronically injured cortical motor neurons retain the capacity to regenerate for extended periods and that regeneration can be stimulated using grafts of minced, preligated autologous peripheral nerve tissue.
Dorsal hippocampal lesions impair appetitive classical conditioning to localized cues
Authors: Bonardi Charlotte 
Published: March 2003

AbstractThree experiments examined appetitive classical conditioning in rats with small electrolytic lesions of the dorsal hippocampus. In all the experiments, the reinforcer was food delivery and the conditioned response (CR) entry to the food tray; the three experiments differed in the nature of the conditioned stimulus (CS). When this was a small light located inside the food tray, conditioning was impaired in lesioned animals, but when the CS was a general increase in illumination, they learned at the same rate as controls. With a white noise as the CS, learning was significantly faster in lesioned subjects. These data demonstrate that lesions of the dorsal hippocampus can produce impairments in appetitive delay conditioning, but only with certain types of CS. It is suggested that deficits are found with CSs that are localized in space.
Odour‐evoked [Ca2+] transients in mitral cell dendrites of frog olfactory glomeruli
Authors: Delaney Kerry , Davison Ian , Denk Winfried 
Published: March 2003

AbstractWe measured Ca2+ concentration, [Ca2+], transients in mitral cell distal apical dendritic tufts produced by physiological odour stimulation of the olfactory epithelium and electrical stimulation of the olfactory nerve (ON) using two‐photon scanning and conventional wide‐field microscopy of Ca2+‐Green‐1 dextran in an in vitro frog nose–brain preparation. Weak or strong ON shock‐evoked fluorescence transients always had short latency with an onset 0–10 ms after the onset of the bulb local field potential, rapidly increasing to a peak of up to 25% fractional fluorescence change (ΔF/F) in 10–30 ms, were blocked by 10 µm CNQX, decaying with a time constant of about 1 s. With stronger ON shocks that activated many receptor axons, an additional, delayed, sustained AP5‐sensitive component (peak at ≈ 0.5 s, up to 40% ΔF/F maximum) could usually be produced. Odour‐evoked [Ca2+] transients sometimes displayed a rapid onset phase that peaked within 50 ms but always had a sustained phase that peaked 0.5–1.5 s after onset, regardless of the strength of the odour or the amplitude of the response. These were considerably larger (up to 150% ΔF/F) than those evoked by ON shock. Odour‐evoked [Ca2+] transients were also distinguished from ON shock‐evoked transients by tufts in different glomeruli responding with different delays (time to onset differed by up to 1.5 s between different tufts for the same odour). Odour‐evoked [Ca2+] transients were increased by AMPA‐kainate receptor blockade, but substantially blocked by AP5. Electrical stimulation of the lateral olfactory tract (5–6 stimuli at 10 Hz) that evoked granule cell feedback inhibition, blocked 60–100% of the odour‐evoked [Ca2+] transient in tufts when delivered within about 0.5 s of the odour. LOT‐mediated inhibition was blocked by 10 µm bicuculline.
The mammalian homologue of the novel peptide Bv8 is expressed in the central nervous system and supports neuronal survival by activating the MAP kinase/PI‐3‐kinase pathways
Authors: Melchiorri D. , Bruno V. , Besong G. , Ngomba R. T. , Cuomo L. , De Blasi A. , Copani A. , Moschella C. , Storto M. , Nicoletti F. , Lepperdinger G. , Passarelli F. 
Published: March 2003

AbstractPrevious studies have identified the mammalian homologue of Bv8 (mBv8), a small protein originally isolated from skin secretions of the frog, Bombina variegata. In situ hybridization showed that mBv8 RNA was widely expressed in the rodent CNS, with high levels being detected in layer II of the cerebral cortex, limbic regions, cerebellar Purkinje cells, and dorsal and ventral horns of the spinal cord. A similar pattern of distribution was found by examining the presence of mBv8 protein by immunocytochemistry. Addition of frog Bv8 to cultured cerebellar granule cells reduced the extent of apoptotic death induced by switching the growing medium from 25 to 5 mm K+. Bv8 could also protect cultured cortical neurons against excitotoxic death. Both effects were prevented by PD98059 and LY294002, which inhibit the mitogen‐activated protein kinase (MAPK) and phosphatidylinositol‐3‐kinase (PI‐3‐K) pathways, respectively. In cultured cerebellar granule cells, Bv8 stimulated both the MAPK and the PI‐3‐K pathways, as revealed by Western blot analysis of phosphorylated p44/p42 MAPKs and phosphorylated Akt, respectively. We conclude that mBv8 acts as an endogenous neurotrophic factor and supports neuronal survival through the activation of the MAPK/PI‐3‐K pathways.
Acute and long‐term changes in the mesolimbic dopamine pathway after systemic or local single nicotine injections
Authors: Ferrari R. , Le Novère N. , Picciotto M. R. , Changeux J. P. , Zoli M. 
Published: March 2003

AbstractWe have examined several neurochemical and behavioural parameters related to the function of the mesolimbic dopamine (DA) pathway in animals treated with nicotine following three modes of drug administration, i.e. systemic intraperitoneal injection, intra‐accumbens (Acb) infusion or intraventral tegmental area (intra‐VTA) microinjection. The present modes of systemic, intra‐Acb and intra‐VTA nicotine administration elicited comparable acute increases in dialysate DA levels from the Acb. The increase in extracellular DA levels was paralleled by a significant enhancement of locomotion in a habituated environment in the case of systemic or intra‐VTA nicotine administration, whereas unilateral or bilateral intra‐Acb nicotine infusion was ineffective, showing that accumbal DA increase is not sufficient to elicit locomotion in this experimental paradigm. Intra‐VTA, but not systemic or intra‐Acb, nicotine administration caused a long‐term (at least 24‐h) increase in basal dialysate DA levels from the Acb. In addition, significant increases in tyrosine hydroxylase (TH) and GluR1 (but not dopamine transporter or NR1) mRNA levels in the VTA were detected 24 h after intra‐VTA nicotine administration. Systemic nicotine injection caused only an increase in TH mRNA levels while intra‐Acb infusion did not modify any of the mRNAs tested. The long‐term increase in basal DA levels in the Acb and TH, and GluR1 mRNA levels in the VTA upon intra‐VTA nicotine microinjection indicates that even a single nicotine injection can induce plastic changes of the mesolimbic DA pathway.
Opposing roles for medial and central amygdala in the initiation of noradrenergic cell responses to a psychological stressor
Authors: Dayas C. V. , Day T. A. 
Published: March 2003

AbstractPsychological stressors trigger the activation of medullary noradrenergic cells, an effect that has been shown to depend upon yet‐to‐be‐identified structures located higher in the brain. To test whether the amygdala is important in this regard, we examined the effects of amygdala lesions on noradrenergic cell responses to restraint, and also looked at whether any amygdala cells that respond to restraint project directly to the medulla. Ibotenic acid lesions of the medial amygdala completely abolished restraint‐induced Fos expression in A1 and A2 noradrenergic cells. In contrast, lesions of the central amygdala actually facilitated noradrenergic cell responses to restraint. Tracer deposits in the dorsomedial (but not ventrolateral) medulla retrogradely labelled many cells in the central nucleus of the amygdala, but none of these cells expressed Fos in response to restraint. These data suggest for the first time that the medial amygdala is critical to the activation of medullary noradrenergic cells by a psychological stressor whereas the central nucleus exerts an opposing, inhibitory influence upon noradrenergic cell recruitment. The initiation of noradrenergic cell responses by the medial amygdala does not involve a direct projection to the medulla. Accordingly, a relay through some other structure, such as the hypothalamic paraventricular nucleus, warrants careful consideration.
Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey
Authors: Petrides M. , Pandya D. N. 
Published: March 2003

AbstractA comparison of the cytoarchitecture of the human and the macaque monkey ventrolateral prefrontal cortex demonstrated a region in the monkey that exhibits the architectonic characteristic of area 45 in the human brain. This region occupies the dorsal part of the ventrolateral prefrontal convexity just below area 9/46v. Rostroventral to area 45 in the human brain lies a large cortical region labelled as area 47 by Brodmann. The ventrolateral component of this region extending as far as the lateral orbital sulcus has architectonic characteristics similar to those of the ventrolateral prefrontal region labelled by Walker as area 12 in the macaque monkey. We designated this region in both the human and the monkey ventrolateral prefrontal cortex as area 47/12. Thus, area 47/12 designates the specific part of the zone previously labelled as area 47 in the human brain that has the same overall architectonic pattern as that of Walker's area 12 in the macaque monkey brain. The cortical connections of these two areas were examined in the monkey by injecting fluorescent retrograde tracers. Although both area 45 and area 47/12 as defined here had complex multimodal input, they could be differentiated in terms of some of their inputs. Retrograde tracers restricted to area 47/12 resulted in heavy labelling of neurons in the rostral inferotemporal visual association cortex and in temporal limbic areas (i.e. perirhinal and parahippocampal cortex). In contrast, injections of tracers into dorsally adjacent area 45 demonstrated strong labelling in the superior temporal gyrus (i.e. the auditory association cortex) and the multimodal cortex in the upper bank of the superior temporal sulcus.
Neuronal responses of the rat amygdala during extinction and reassociation learning in elementary and configural associative tasks
Authors: Toyomitsu Yuji , Nishijo Hisao , Uwano Teruko , Kuratsu Junichi , Ono Taketoshi 
Published: March 2003

AbstractTo investigate functional heterogeneity within the amygdala in appetitive conditioned instrumental behaviours, neuronal activity was recorded from the amygdala of behaving rats during learning and discrimination of conditioned sensory stimuli associated with or without reinforcement [sucrose solution, intracranial self‐stimulation (ICSS)]. Sensory stimuli included auditory (tone), visual (light) and configural (simultaneous presentation of tone and light) stimuli. The rat was trained to lick a spout protruded close to its mouth just after a conditioned sensory stimulus to obtain a reward. Of the 609 neurons recorded from the amygdala and amygdalostriatal transition area, 154 responded to one or more sensory stimuli. The 62 amygdalar neurons responded strongly to certain conditioned sensory stimuli associated with rewards. Of these 62 neurons, 45 were tested with the extinction trials. Responses of 31 neurons to conditioned stimuli were finally extinguished, and those of the remaining 14 were not extinguished. Furthermore, responses of 26 of these 31 neurons resumed in the relearning trials (plastic neurons), suggesting that these sensory responses were associative rather than just responses to physical properties of the stimuli. These plastic neurons were located mainly in the basolateral nucleus of the amygdala, and responses of the plastic neurons were correlated with behavioural responses. These results suggest that the basolateral nucleus is crucial in associative learning between sensory information and affective significance for behavioural outputs in appetitive conditioned instrumental behaviours.
Differential post‐transcriptional regulation of p21WAF1/Cip1 levels in the developing nervous system following γ‐irradiation
Authors: Herzog Karl‐Heinz , Braun Johann S. , Han Sung‐Ho , Morgan James I. 
Published: March 2003

AbstractRadiation‐induced death in the developing brain is p53‐dependent. However, genetic studies indicate that the signalling pathways that couple irradiation to p53 expression can vary between different developing neural populations [Herzog et al. (1998)Science, 280, 1089–1091]. Here we establish that signalling downstream of p53 also exhibits brain region‐specific differences that are associated with the relative vulnerability of some cell populations to radiation‐induced killing in the mouse. Following γ‐irradiation, p53 and p21WAF1/cip1, but not Bax, protein levels increased in the developing cerebellum. In contrast, neither p21WAF1/cip1 nor Bax protein levels were elevated in the retina following irradiation, despite increased p53 expression. In the retina, p53 expression was associated with cells destined to die, whereas in the cerebellum, p53 was expressed in both radiation‐sensitive and radiation‐resistant neuroblasts of the external granule cell layer. Although p21WAF1/cip1 mRNA was expressed in all p53‐positive neuroblasts after irradiation, p21WAF1/cip1 protein was only detected in radiation‐resistant neuroblasts of the cerebellum. Thus, p21WAF1/cip1 was subject to post‐transcriptional regulation with p21WAF1/cip1 protein only accumulating in cells destined to survive irradiation. Nevertheless, p21WAF1/cip1 function was not essential for radiation resistance, as postmitotic neuroblasts in the external granule cell layer were spared in p21WAF1/cip1 knockout mice.
A dose‐dependent facilitation and inhibition of peripheral nerve regeneration by brain‐derived neurotrophic factor
Authors: Boyd J. G. , Gordon T. 
Published: March 2003

AbstractThe time‐dependent decline in the ability of motoneurons to regenerate their axons after axotomy is one of the principle contributing factors to poor functional recovery after peripheral nerve injury. A decline in neurotrophic support may be partially responsible for this effect. The up‐regulation of BDNF after injury, both in denervated Schwann cells and in axotomized motoneurons, suggests its importance in motor axonal regeneration. In adult female Sprague–Dawley rats, we counted the number of freshly injured or chronically axotomized tibial motoneurons that had regenerated their axons 1 month after surgical suture to a freshly denervated common peroneal distal nerve stump. Motor axonal regeneration was evaluated by applying fluorescent retrograde neurotracers to the common peroneal nerve 20 mm distal to the injury site and counting the number of fluorescently labelled motoneurons in the T11–L1 region of the spinal cord. We report that low doses of BDNF (0.5–2 µg/day for 28 days) had no detectable effect on axonal regeneration after immediate nerve repair, but promoted axonal regeneration of motoneurons whose regenerative capacity was reduced by chronic axotomy 2 months prior to nerve resuture, completely reversing the negative effects of delayed nerve repair. In contrast, high doses of BDNF (12–20 µg/day for 28 days) significantly inhibited motor axonal regeneration, after both immediate nerve repair and nerve repair after chronic axotomy. The inhibitory actions of high dose BDNF could be reversed by functional blockade of p75 receptors, thus implicating these receptors as mediators of the inhibitory effects of high dose exogenous BDNF.
GDNF and NGF released by synthetic guidance channels support sciatic nerve regeneration across a long gap
Authors: Fine Eric G. , Decosterd Isabelle , Papaloïzos Michael , Zurn Anne D. , Aebischer Patrick 
Published: March 2003

AbstractThe present work was performed to determine the ability of neurotrophic factors to allow axonal regeneration across a 15‐mm‐long gap in the rat sciatic nerve. Synthetic nerve guidance channels slowly releasing NGF and GDNF were fabricated and sutured to the cut ends of the nerve to bridge the gap. After 7 weeks, nerve cables had formed in nine out of ten channels in both the NGF and GDNF groups, while no neuronal cables were present in the control group. The average number of myelinated axons at the midpoint of the regenerated nerves was significantly greater in the presence of GDNF than NGF (4942 ± 1627 vs. 1199 ± 431, P ≤ 0.04). A significantly greater number of neuronal cells in the GDNF group, when compared to the NGF group, retrogradely transported FluoroGold injected distal to the injury site before explantation. The total number of labelled motoneurons observed in the ventral horn of the spinal cord was 98.1 ± 23.4 vs. 20.0 ± 8.5 (P ≤ 0.001) in the presence of GDNF and NGF, respectively. In the dorsal root ganglia, 22.7% ± 4.9% vs. 3.2% ± 1.9% (P ≤ 0.005) of sensory neurons were labelled retrogradely in the GDNF and NGF treatment groups, respectively. The present study demonstrates that, sustained delivery of GDNF and NGF to the injury site, by synthetic nerve guidance channels, allows regeneration of both sensory and motor axons over long gaps; GDNF leads to better overall regeneration in the sciatic nerve.
Dose‐dependent rescue of axotomized rat retinal ganglion cells by adenovirus‐mediated expression of glial cell‐line derived neurotrophic factorin vivo
Authors: Schmeer Christian , Straten Guido , Kügler Sebastian , Gravel Claude , Bähr Mathias , Isenmann Stefan 
Published: March 2003

AbstractAdult rat retinal ganglion cells undergo degeneration after optic nerve transection. Repeated intraocular injection of glial cell‐line derived neurotrophic factor (GDNF) has been shown to be efficient in enhancing retinal ganglion cell survival following optic nerve axotomy. In the present study we evaluated the potential survival‐promoting effect of adenovirally administered GDNF on axotomized retinal ganglion cells. A single intravitreal injection [7 × 107 plaque‐forming units (pfu) or 7 × 108 pfu] of an adenoviral vector expressing the rat GDNF gene from a cytomegalovirus promoter enhanced retinal ganglion cell survival 14 days after axotomy by 67 and 125%, respectively, when compared to control animals. Intraocular administration of the vector rescued 12.6 and 23%, respectively, of the retinal ganglion cells which would otherwise have died after axotomy. An increase in retinal GDNF protein and specific virally transduced GDNF mRNA expression was detected following intraocular vector application. Our data support previous findings showing that adenoviral delivery of neurotrophic factors to the vitreous body is a feasible approach for the prevention of axotomy‐induced retinal ganglion cell death in vivo and may constitute a relevant strategy for future treatment in traumatic brain injury and ensuing neurodegeneration.
Hypothalamic bHLH transcription factors are novel candidates in the regulation of energy balance
Authors: Nilaweera Kanishka N. , Ellis Claire , Barrett Perry , Mercer Julian G. , Morgan Peter J. 
Published: March 2003

AbstractThe basic helix–loop–helix transcription factors, neurological basic‐helix–loop–helix‐2 (Nhlh‐2), neurogenic differentiation‐1 (NeuroD‐1) and single minded‐1 (Sim‐1) could have roles in energy balance regulation, although supporting evidence is inconclusive. This study in mice provides further evidence that Nhlh‐2 and NeuroD‐1 are involved in energy balance regulation. In situ hybridization was used to study the expression of the genes in relation to physiological status and genetic background within hypothalamic nuclei that are involved in energy balance regulation. These studies show reduced expression of Nhlh‐2 mRNA in the arcuate (ARC) nucleus and NeuroD‐1 mRNA in the paraventricular (PVN) nucleus in obese ob/ob and 24 h food‐deprived mice relative to respective controls, suggesting regulation by leptin. Interestingly, Nhlh‐2 mRNA expression is reduced in obese db/db mice, whereas NeuroD‐1 remains unchanged, suggesting different mechanisms of regulation by leptin of these two genes. To study the role of leptin in the regulation of these genes, leptin was injected intraperitoneally in obese ob/ob mice and mRNA expression evaluated after 1 h or 4 h, or after twice‐daily injection for 7 days. None of these regimes restored Nhlh‐2 or NeuroD‐1 to wild‐type mRNA levels. These latter data suggest either that the regulation of the Nhlh‐2 and NeuroD‐1 genes by leptin is indirect or that the apparent leptin insensitivity of the gene expression reflects a developmental deficit that is a consequence of the phenotype of the obese ob/ob mice. The relationship between Nhlh‐2 and candidate energy balance‐related genes was studied by dual in situ hybridization. Nhlh‐2 mRNA was coexpressed in a subpopulation (30%) of ARC neurons expressing pro‐opiomelanocortin (POMC) mRNA, suggesting a potential functional relationship.
Haematopoietic progenitor cells from adult bone marrow differentiate into cells that express oligodendroglial antigens in the neonatal mouse brain
Authors: Bonilla Sonia , Alarcón Pedro , Villaverde Ramón , Aparicio Pedro , Silva Augusto , Martínez Salvador 
Published: March 2003

AbstractStem cells are self‐renewable, pluripotent cells that, in adult life, proliferate by a characteristic asymmetric division in which one daughter cell is committed to differentiation whereas the other remains a stem cell. These cells are also characterized by their ability to differentiate into various cell types under heterotopic environmental influences. In the present study, we have explored the potential of adult haematopoietic bone marrow cells to differentiate into cells of oligodendroglial lineage under physiological, active myelinating conditions. We present evidence of generation of cells expressing oligodendroglial specific markers from a bone marrow subpopulation enriched on adult haematopoietic progenitor cells (CD117+) in vivo after intracerebral transplantation into the neonatal mouse brain. Our results suggest that adult bone marrow cells have the capacity to undergo differentiation from haematopoietic to oligodendroglial cells and add support the validity of bone marrow transplants as an alternative treatment for demyelinating diseases of the CNS including Multiple Sclerosis.