bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inducible nitric oxide synthase activity induced by sodium chloride solution prolongs luminal pH elevation in rat and mouse stomachs
Authors: TATEMICHI MASAYUKI , OGURA TSUTOMU , SAKURAZAWA NOBUYUKI , NAGATA HIROSHI , SUGITA MINORU , ESUMI HIROYASU 
Published: August 2003

AbstractBackground:  Sodium chloride (NaCl) is a strong promoter of gastric cancer. We hypothesized that inducible nitric oxide synthase (iNOS) induced by NaCl may be involved in its promoting effects. We investigated iNOS expression by hypertonic NaCl solutions and its pathophysiological roles in the gastric mucosa of rats and mice.Methods:  iNOS mRNA and protein expressions were examined in the rat and mouse gastric mucosa after intragastric administration of NaCl solution by northern blot, reverse transcription‐polymerase chain reaction (RT‐PCR) and immunohistochemistry. The effect on luminal pH by iNOS activity was assessed using aminoguanidine, a potent iNOS inhibitor, and iNOS gene deficient (iNOS–/–) mice.Results:  iNOS expression was detected at concentrations higher than 1.7 M, mainly in the cells infiltrating the damaged mucosa of rats. Administration of a higher than 3.4 M NaCl solution elevated luminal pH of the rat stomach remarkably, enabling bacterial overgrowth and dramatically increasing iNOS expression (n = 5 per concentration). Pretreatment with ampicillin (p.o), an antibiotic, attenuated the iNOS expression in duplicate experiments. Co‐treatment with aminoguanidine (s.q) accelerated recovery of elevated luminal pH at 8 h and 16 h or 24 h after administration of 3.4 M (n = 8) and 5.2 M NaCl solution (n = 5), respectively. iNOS expression and luminal pH elevation were also observed in mice stomachs after administration of 3.4 M NaCl solution. The elevated luminal pH of iNOS–/– mice stomachs after the administration of NaCl solution was significantly lower at 6 h (n = 7) and at 9 h (n = 11), compared to that of wild type mice (n = 9 and 10, respectively).Conclusions:  Hypertonic NaCl solutions induced iNOS expression in the gastric mucosa. iNOS activity prolonged the elevation of the luminal pH, potentially leading to bacterial overgrowth, which in turn enhanced iNOS expression. This vicious cycle might be related to the promoting effect of NaCl.
Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer
Authors: GIBSON RACHEL J , BOWEN JOANNE M , INGLIS MARK RB , CUMMINS ADRIAN G , KEEFE DOROTHY MK 
Published: August 2003

AbstractBackground and Aims:  Irinotecan (CPT‐11) is a chemotherapeutic drug for cancer that causes severe diarrhea by an uncertain mechanism. The aim of the present study was to investigate the time‐course of apoptosis and whole intestinal damage after irinotecan to further elucidate the mechanism behind the diarrhea.Methods:  Groups of breast cancer‐bearing dark agouti (DA) rats were treated with 100, 150 or 200 mg/kg doses of irinotecan or vehicle control daily for two days, and killed at 6, 24, 72 or 96 h after treatment. Apoptosis and morphometry were examined in both the small and large intestines. Histopathology and goblet cell numbers were recorded. Data were analyzed using the Peritz′F‐test.Results:  Irinotecan increased apoptosis and caused villous atrophy and crypt hypoplasia in the small intestine, and increased apoptosis, crypt hypoplasia, crypt dilation and mucus secretion in the large intestine. Irinotecan at 100 and 150 mg/kg caused crypt hypoplasia at 6 and 24 h, with rebound hyperplasia at 72 and 96 h. At 200 mg/kg, irinotecan caused a more pronounced crypt hypoplasia earlier and all animals died by 96 h. Apoptosis peaked at 6 h and remained elevated over the remainder of the time‐points. This was not dose‐dependent. Irinotecan at all doses altered colonic, but not jejunal, goblet cells. Irinotecan increased colonic mucus secretion.Conclusions:  We conclude that irinotecan causes diarrhea by inducing apoptosis and hypoproliferation in both the small and large intestines, and causes colonic damage with changes in goblet cells and mucin secretion.
Hyperexcitability of intact neurons underlies acute development of trauma‐related electrographic seizures in cats in vivo
Authors: Topolnik Lisa , Steriade Mircea , Timofeev Igor 
Published: August 2003

AbstractCortical trauma can lead to development of electrographic paroxysmal activities. Current views of trauma‐induced epileptogenesis suggest that chronic neuronal hyperexcitability and extensive morphological reorganization of the traumatized cortex are required for the generation of electrographic seizures. However, the mechanisms responsible for the initiation of electrographic seizures shortly after cortical injury are poorly understood. Here we show that, in the experimental model of partially deafferented (undercut) cortex, an increase in intrinsic and synaptic excitability of neurons in areas adjacent to the undercut cortex is sufficient for the generation of electrographic paroxysmal activity within few hours after partial cortical deafferentation. Locally increased and spatially restricted neuronal excitability arose from the increased incidence of intrinsically bursting neurons, enhanced intrinsic and synaptic neuronal responsiveness, and slight disinhibition. These mechanisms only operate in neurons located in the vicinity of partially deafferented sites because, after the cortical injury, partially deafferented neurons are mostly silent and hypoexcitable. Our results suggest that trauma‐induced electrographic seizures first arise in cortical fields that are closest to the site of injury and such seizures do not require long‐term neuronal reorganization.
A double dissociation between serial reaction time and radial maze performance in rats subjected to 192 IgG‐saporin lesions of the nucleus basalis and/or the septal region
Authors: Lehmann O. , Grottick A. J. , Cassel J. ‐C. , Higgins G. A. 
Published: August 2003

AbstractThe cholinergic basal forebrain has been implicated in aspects of cognitive function including memory and attention, but the precise contribution of its major components, the basalocortical and the septohippocampal systems, remains unclear. Rats were subjected to lesions of either the nucleus basalis magnocellularis (Basalis), the medial septum/vertical limb of the diagonal band of Broca (Septum), or both nuclei (Basalis + Septum), using the selective cholinotoxin 192 IgG‐saporin. Cognitive performance was evaluated in tasks taxing attention (the five‐choice serial reaction time task, 5‐CSRTT) and spatial working memory (radial arm maze, RAM). Nucleus basalis lesions disrupted performance of the 5‐CSRTT, as demonstrated by decreased choice accuracy, increased incidence of missed trials, increased latencies to respond correctly, and a disrupted pattern of response control. Combined lesions of the Basalis and Septum resulted in qualitatively similar deficits to Basalis lesions alone, although interestingly, these rats were unimpaired on measures of response speed, and showed weaker deficits on accuracy and omissions. Decreasing the attentional load by lengthening stimulus duration reversed some of the deficits in Basalis and Basalis + Septum rats, suggesting an attentional deficit rather than motivation or motor perturbations. Performance in rats with septal lesions was only affected when task difficulty was increased. In the RAM an opposing pattern of effects was observed, with Septum and Basalis + Septum rats showing dramatic impairments, and Basalis rats performing normally. Taken together, these data provide clear evidence for a functional dissociation between septohippocampal and basalocortical cholinergic systems in aspects of cognitive function.
Multipleacegenes encoding acetylcholinesterases ofCaenorhabditis eleganshave distinct tissue expression
Authors: Combes Didier , Fedon Yann , Toutant Jean‐Pierre , Arpagaus Martine 
Published: August 2003

Abstractace‐1andace‐2genes encoding acetylcholinesterase in the nematodeCaenorhabditis eleganspresent 35% identity in coding sequences but no homology in noncoding regions (introns, 5′‐ and 3′‐untranslated regions). A 5′‐region oface‐2was defined by rescueof ace‐1;ace‐2mutants. When green fluorescent protein (GFP) expression was driven by this regulatory region, the resulting pattern was distinct from that oface‐1. This latter gene is expressed in all body‐wall and vulval muscle cells (Culettoet al., 1999), whereasace‐2is expressed almost exclusively in neurons.ace‐3andace‐4genes are located in close proximity on chromosome II (Combeset al., 2000). These two genes were first transcribedin vivoas a bicistronic messenger and thus constitute anace‐3;ace‐4operon. However, there was a very low level of monocistronic mRNA oface‐4(the upstream gene)in vivo, and no ACE‐4 enzymatic activity was ever detected. GFP expression driven by a 5′ upstream region of theace‐3;ace‐4operon was detected in several muscle cells of the pharynx (pm3, pm4, pm5 and pm7) and in the two canal associated neurons (CAN cells). A dorsal row of body‐wall muscle cells was intensively labelled in larval stages but no longer detected in adults. The distinct tissue‐specific expression oface‐1,ace‐2andace‐3(coexpressed only in pm5 cells) indicates thatacegenes are not redundant.
N‐methyl‐d‐aspartate‐triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c‐Jun N‐terminal kinase pathway
Authors: Borsello Tiziana , Croquelois Karine , Hornung Jean‐Pierre , Clarke Peter G. H. 
Published: August 2003

AbstractAcute excitotoxic neuronal death was studied in rat organotypic hippocampal slices exposed to 100 µmN‐methyl‐d‐aspartate. Fulgurant death of pyramidal neurons occurred in the CA1 and CA3 regions and was already detectable within 2 h of the N‐methyl‐d‐aspartate administration. Morphologically, the neuronal death was neither apoptotic nor necrotic but had the hallmarks of autophagic neuronal death, as shown by acid phosphatase histochemistry in both CA1 and CA3 and by electron microscopy in CA1. The dying neurons also manifested strong endocytosis of horseradish peroxidase or microperoxidase, occurring probably by a fluid phase mechanism, and followed, surprisingly, by nuclear entry. In addition to these autophagic and endocytic characteristics, there were indications that the c‐Jun N‐terminal kinase pathway was activated. Its target c‐Jun was selectively phosphorylated in CA1, CA3 and the dentate gyrus and c‐Fos, the transcription of which is under the positive control of c‐Jun N‐terminal kinase target Elk1, was selectively up‐regulated in CA1 and CA3. All these effects, the neuronal death itself and the associated autophagy and endocytosis, were totally prevented by a cell‐permeable inhibitor of the interaction between c‐Jun N‐terminal kinase and certain of its targets. These results show that pyramidal neurons undergoing excitotoxic death in this situation are autophagic and endocytic and that both the cell death and the associated autophagy and endocytosis are under the control of the c‐Jun N‐terminal kinase pathway.
Potentiation of amygdaloid and hippocampal auditory‐evoked potentials in a discriminatory fear‐conditioning task in mice as a function of tone pattern and context
Authors: Tang Jianrong , Wagner Stefanie , Schachner Melitta , Dityatev Alexander , Wotjak Carsten T. 
Published: August 2003

AbstractAccording to the local memory storage hypothesis, information about the tone–shock association in an auditory fear‐conditioning paradigm is stored in synapses within the lateral amygdala. Thus, fear‐conditioning‐induced potentiation of auditory‐evoked potentials in response to a conditioned stimulus (CS+, a series of short lasting tones; patterned tone) has been interpreted as an in vivo correlate of amygdaloid synaptic plasticity. Here, we re‐examine the specificity of potentiation of auditory‐evoked potentials in terms of (i) local confinement to the lateral amygdala, (ii) parameters of CS+ and (iii) influence of context, using a discriminatory fear‐conditioning paradigm. Adult male C57BL/6J mice were implanted with recording electrodes aimed at the lateral amygdala, the CA1 region of the hippocampus and the neck muscles for simultaneous recordings of auditory‐evoked potentials and startle responses. In a neutral context, auditory‐evoked potentials within lateral amygdala and CA1 as well as startle and freezing responses to the CS+ were significantly potentiated following conditioning, as compared with pre‐conditioning values and responses to a neutral stimulus (CSn; tone of different frequency). Potentiation was only evident if CS+ was presented as a uniform series but not if presented mixed with CSn. Accordingly, mice failed to show intensified freezing to a patterned tone if a single lasting tone of the same frequency served as CS+. Both CA1 and lateral amygdala auditory‐evoked potentials were potentiated in response to CSn if presented in the conditioning context. These findings demonstrate that (i) potentiation of auditory‐evoked potentials is not restricted to the lateral amygdala, (ii) both tone frequency and pattern of tone presentation are essential for proper CS+ recognition and (iii) contextual memory leads to a general potentiation of auditory‐evoked potentials.
Too much of a good thing: retinoic acid as an endogenous regulator of neural differentiation and exogenous teratogen
Authors: McCaffery P. J. , Adams J. , Maden M. , Rosa‐Molinar E. 
Published: August 2003

AbstractRetinoic acid (RA) is essential for both embryonic and adult growth, activating gene transcription via specific nuclear receptors. It is generated, via a retinaldehyde intermediate, from retinol (vitamin A). RA levels require precise regulation by controlled synthesis and catabolism, and when RA concentrations deviate from normal, in either direction, abnormal growth and development occurs. This review describes: (i) how the pattern of RA metabolic enzymes controls the actions of RA; and (ii) the type of abnormalities that result when this pattern breaks down. Examples are given of RA control of the anterior/posterior axis of the hindbrain, the dorsal/ventral axis of the spinal cord, as well as certain sex‐specific segments of the spinal cord, using varied animal models including mouse, quail and mosquitofish. These functions are highly sensitive to abnormal changes in RA concentration. In rodents, the control of neural patterning and differentiation are disrupted when RA concentrations are lowered, whereas inappropriately high concentrations of RA result in abnormal development of cerebellum and hindbrain nuclei. The latter parallels the malformations seen in the human embryo exposed to RA due to treatment of the mother with the acne drug Accutane (13‐cisRA) and, in cases where the child survives beyond birth, a particular set of behavioural anomalies can be described. Even the adult brain may be susceptible to an imbalance of RA, particularly the hippocampus. This report shows how the properties of RA as a neural induction agent and organizer of segmentation can explain the consequences of RA depletion and overexpression.
Direction‐selective motion blindness after unilateral posterior brain damage
Authors: Blanke Olaf , Landis Theodor , Mermoud Christophe , Spinelli Laurent , Safran Avinoam B. 
Published: August 2003

AbstractMotion blindness (MB) is defined as the selective disturbance of visual motion perception despite intact perception of other features of the visual scene. MB is characterized by a pandirectional deficit of motion direction discrimination and is assumed to result from damage to the visual motion pathway, especially area MT/V5. However, the most characteristic feature of primate MT/V5 neurons is not their motion selectivity but their preference for one direction of motion (direction selectivity), which changes incrementally at neighbouring columns. In addition to this microscopic directional organization, studies in nonhuman and human primates suggest that single directions of motion are also coded at a more macroscopic level. We thus hypothesized that if MB in humans results from damage to direction‐selective neurons in the visual motion pathway, posterior brain damage might cause MB which is direction selective, not pandirectional. The present study investigated motion direction discrimination in patients with posterior unilateral brain damage and determined separate psychophysical thresholds for the four cardinal directions. In addition, we analysed whether the direction of erroneous motion perception (i.e. the perception of right motion for upward motion) was random or showed a directional bias. We report three principal findings. First, motion direction discrimination was severely impaired in one or two directions while it was normal in the other directions. This constituted direction‐selective MB. Second, MB was characterized not only by a quantitative direction‐selective increase in psychophysical thresholds but also by a qualitative impairment of perceiving motion direction systematically in wrong directions. Both findings suggest that the cortical modules specialized for the perception of a single direction of motion might be larger than previously thought. Third, lesion analysis showed that unilateral damage, not only the human homologue of MT/V5 but also to parieto‐occipital cortex, leads to MB.
NMDA lesions of Ammon's horn and the dentate gyrus disrupt the direct and temporally paced homing displayed by rats exploring a novel environment: evidence for a role of the hippocampus in dead reckoning
Authors: Wallace Douglas G. , Whishaw Ian Q. 
Published: August 2003

AbstractDead reckoning, a form of navigation used to locate a present position and to return to a starting position, is used by rats to return to their home base. The present experiment examined whether dead reckoning is displayed by rats during their first exploratory excursions in a novel environment and also examined whether the behaviour requires the integrity of the cells of the hippocampus. Experimental rats, those with NMDA (N‐methly d‐aspartate) lesions of Ammon's horn and the dentate gyrus, and control rats could leave a cage to explore a large circular table under light and dark conditions. Home base behaviour, use of olfactory cues, and thigmotaxic‐ based navigation were evaluated. Temporal, topographical and kinematic analyses were conducted on the first three exploratory excursions that extended at least halfway across the table. Groups did not differ in numbers of exits from the home base, lingering near the home base, distance travelled, or the use of surface cues as might be exemplified by thigmotaxic and olfactory behaviour. Temporal, topographical and kinematic reconstructions of homing behaviour, however, indicated that control rats, but not hippocampal rats, made direct high velocity return trips to the home base in both the light and the dark. Peak velocity of the trips occurred at the trip midpoint, independent of trip distance, suggesting the movements were preplanned. These results are discussed in relation to the ideas that dead reckoning is used in the homing of exploring rats and that this form of navigation involves the hippocampus.
Mechanisms of sensitization of the response of single dorsal root ganglion cells from adult rat to noxious heat
Authors: Galoyan Samuel M. , Petruska Jeffrey C. , Mendell Lorne M. 
Published: August 2003

AbstractWe investigated the regulation by nerve growth factor of the response of sensory neurons to noxious heat (>43 °C). In dissociated dorsal root ganglion neurons (<30 µm) from adult rat we demonstrated, using perforated patch clamp recording, that the inward current elicited in response to noxious heating is enhanced by nerve growth factor and reduced by capsazepine. The tachyphylaxis observed in response to the second of two heat pulses was reversed in most cells when nerve growth factor was introduced into the medium during the 5 min between the two heat stimuli, similar to findings using capsaicin [X. Shu & L.M. Mendell (1999) Neurosci. Lett.274, 159–162]. The threshold temperature did not change systematically after nerve growth factor. Using antibodies to TRPV1 and trkA in a subset of cells from which we recorded, we found a virtually perfect correlation between expression of TRPV1 and sensitivity to noxious heat. In addition, trkA expression was perfectly correlated with the ability of nerve growth factor to reverse tachyphylaxis. Thus, this physiological test is a reliable measure of trkA expression in cells sensitive to noxious heat. In agreement with studies in heterologous cells expressing trkA and TRPV1, pharmacologically blocking phospholipase C abolished the effect of nerve growth factor on heat‐evoked currents in cells verified to express trkA. We conclude that the response of dorsal root ganglion neurons to noxious heat is conditioned by nerve growth factor in the same way as their response to capsaicin and that these responses require the presence of trkA and TRPV1.
Corticotropin‐releasing factor receptor types 1 and 2 are differentially expressed in pre‐ and post‐synaptic elements in the post‐natal developing rat cerebellum
Authors: Swinny J. D. , Kalicharan D. , Blaauw E. H. , Ijkema‐Paassen J. , Shi F. , Gramsbergen A. , Van Der Want J. J. L. 
Published: August 2003

AbstractCorticotropin‐releasing factor (CRF)‐like proteins act via two G‐protein‐coupled receptors (CRF‐R1 and CRF‐R2) playing important neuromodulatory roles in stress responses and synaptic plasticity. The cerebellar expression of corticotropin‐releasing factor‐like ligands has been well documented, but their receptor localization has not. This is the first combination of a light microscopic and ultrastructural study to localize corticotropin‐releasing factor receptors immunohistologically in the developing rat cerebellum. Both CRF‐R1 and CRF‐R2 were expressed in climbing fibres from early stages (post‐natal day 3) to the adult, but CRF‐R2 immmunoreactivity was only prominent throughout the molecular layer in the posterior cerebellar lobules. CRF‐R1 immunoreactivity was concentrated in apical regions of Purkinje cell somata and later in primary dendrites exhibiting a diffuse cytoplasmic appearance. In Purkinje cells, CRF‐R1 immunoreactivity was never membrane bound post‐synaptically in dendritic spines while CRF‐R2 immunoreactivity was found on plasmic membranes of Purkinje cells from post‐natal day 15 onwards. We conclude that the localization of these receptors in cerebellar afferents implies their pre‐synaptic control of the release of corticotropin‐releasing factor‐like ligands, impacting on the sensory information being transmitted from afferents. Furthermore, the fact that CRF‐R2 is membrane bound at synapses, while CRF‐R1 is not, suggests that ligands couple to CRF‐R2 via synaptic transmission and to CRF‐R1 via volume transmission. Finally, the distinct expression profiles of receptors along structural domains of Purkinje cells suggest that the role for these receptors is to modulate afferent inputs.