bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different α2 adrenoceptor subtypes control noradrenaline release and cell firing in the locus coeruleus of wildtype and monoamine oxidase‐A knockout mice
Authors: Owesson Catarina Å. , Seif Isabelle , McLaughlin Daniel P. , Stamford Jonathan A. 
Published: July 2003

AbstractIn this study, we investigated which subtype(s) of α2‐adrenoceptor control stimulated noradrenaline (NA) release and noradrenergic cell firing in the locus coeruleus (LC) of monoamine oxidase‐A knockout (MAO‐A KO) and C3H/HeJ wildtype mice. On short stimulus trains (10 pulses, 200 Hz), the α2 agonist dexmedetomidine (10 nm) reduced NA efflux by 78 ± 8% and 51 ± 8% in wildtype and MAO‐A KO mice, respectively. In both strains, BRL 44408 (100 nm) and ARC 239 (100 nm) each partially blocked the effect of dexmedetomidine. In MAO‐A KO mice, BRL 44408 (100 nm) increased evoked NA efflux on short trains while ARC 239 (100 nm) had no effect. The two antagonists in combination increased NA efflux (by 81 ± 34%, P < 0.001), significantly more than by BRL 44408 alone. Conversely, in wildtype mice, the α2‐adrenoceptor antagonists did not significantly increase LC NA efflux. On long stimuli (30 pulses, 10 Hz), NA efflux was increased by BRL 44408 (P < 0.001) but not by ARC 239. The effect of BRL 44408 was significantly greater in MAO‐A KO than wildtype mice (208 ± 43% vs. 113 ± 31% increase, P < 0.001). When we examined noradrenergic cell firing, we found that dexmedetomidine inhibited LC cell firing in both strains with comparable EC50 values (2–5 nm), although Emax was significantly lower in MAO‐A KO mice (P < 0.001). The agonist effect was antagonized by BRL 44408 (P < 0.001) in wildtype but not in MAO‐A KO mice, with a pKB of 7.75. ARC 239 had no effect on the agonist response in either strain. A combination of the antagonists was no more effective than BRL 44408 alone (in wildtypes) and had no effect in MAO‐A KO mice. Neither BRL 44408 nor ARC 239 affected basal LC cell firing in wildtype or MAO‐A KO mice. Collectively, these results suggest that, analogous to other monoamine cell groups, there are differences in the autoreceptor populations controlling NA efflux and LC cell firing and that important differences exist between MAO‐A KO and wildtype mice
Differential display implicates cyclophilin A in adult cortical plasticity
Authors: Arckens Lutgarde , Van der Gucht Estel , Van den Bergh Gert , Massie Ann , Leysen Inge , Vandenbussche E. , Eysel Ulf T. , Huybrechts Roger , Vandesande Frans 
Published: July 2003

AbstractRemoval of retinal input from a restricted region of adult cat visual cortex leads to a substantial reorganization of the retinotopy within the sensory‐deprived cortical zone. Little is known about the molecular mechanisms underlying this reorganization. We used differential mRNA display (DDRT‐PCR) to compare gene expression patterns between normal control and reorganizing visual cortex (area 17–18), 3 days after induction of central retinal lesions. Systematic screening revealed a decrease in the mRNA encoding cyclophilin A in lesion‐affected cortex. In situ hybridization and competitive PCR confirmed the decreased cyclophilin A mRNA levels in reorganizing cortex and extended this finding to longer postlesion survival times as well. Western blotting and immunocytochemistry extended these data to the protein level. In situ hybridization and immunocytochemistry further demonstrated that cyclophilin A mRNA and protein are present in neurons. To exclude the possibility that differences in neuronal activity per se can induce alterations in cyclophilin A mRNA and protein expression, we analyzed cyclophilin A expression in the dorsal lateral geniculate nucleus (dLGN) of retinally lesioned cats and in area 17 and the dLGN of isolated hemisphere cats. In these control experiments cyclophilin A mRNA and protein were distributed as in normal control subjects indicating that the decreased cyclophilin A levels, as observed in sensory‐deprived area 17 of retinal lesion cats, are not merely a reflection of changes in neuronal activity. Instead our findings identify cyclophilin A, classically considered a housekeeping gene, as a gene with a brain plasticity‐related expression in the central nervous system.
Identification of a novel alternative splicing isoform of human amyloid precursor protein gene, APP639
Authors: Tang Ke , Wang Chen , Shen Chengyong , Sheng Shuli , Ravid Rivka , Jing Naihe 
Published: July 2003

AbstractSenile plaques, neurofibrillary tangles and amyloid‐laden cerebral vessels are characteristic features in the brains of individuals with Alzheimer's disease (AD). The principal component of amyloid in senile plaque and amyloid‐laden cerebral vessels is β‐amyloid (Aβ), a peptide proteolytically derived from a large amyloid precursor protein (APP). To date, several alternatively spliced human APP transcripts have been described. Here, we report the identification of a novel alternative splicing isoform of the human APP gene, APP639, which excludes exon 2 as well as exons 7 and 8. RT‐PCR and Southern blot analysis show that APP639 mRNA is expressed in many human fetal tissues. In contrast, the APP639 transcript is hardly detected in the aged human cerebral cortex from both pathologically confirmed sporadic AD cases and nondemented controls. However, APP639 mRNA exists in the adult human liver. Western blot analysis shows that the protein product produced from the APP639 cDNA could be recognized by the APP antibody, and it does lack the exon 2 coding region. These results suggest that APP639, a novel alternative splicing isoform of human APP gene, does exist in human tissues in vivo.
Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus
Authors: Ohno‐Shosaku Takako , Matsui Minoru , Fukudome Yuko , Shosaku Jumpei , Tsubokawa Hiroshi , Taketo Makoto M. , Manabe Toshiya , Kano Masanobu 
Published: July 2003

AbstractThe cholinergic system is crucial for higher brain functions including learning and memory. These functions are mediated primarily by muscarinic acetylcholine receptors (mAChRs) that consist of five subtypes (M1–M5). A recent study suggested a novel role of acetylcholine as a potent enhancer of endocannabinoid signalling that acts retrogradely from postsynaptic to presynaptic neurons. In the present study, we further investigated the mechanisms of this cholinergic effect on endocannabinoid signalling. We made paired whole‐cell recordings from cultured hippocampal neurons, and monitored inhibitory postsynaptic currents (IPSCs). The postsynaptic depolarization induced a transient suppression of IPSCs (DSI), a phenomenon known to involve retrograde signalling by endocannabinoids. The cholinergic agonist carbachol (CCh) markedly enhanced DSI at 0.01–0.3 µm without changing the presynaptic cannabinoid sensitivity. The facilitating effect of CCh on DSI was mimicked by the muscarinic agonist oxotremorine‐M, whereas it was eliminated by the muscarinic antagonist atropine. It was also blocked by a non‐hydrolizable analogue of GDP (GDP‐β‐S) that was applied intracellularly to postsynaptic neurons. The muscarinic enhancement of DSI persisted to a substantial degree in the neurons prepared from M1‐knockout and M3‐knockout mice, but was virtually eliminated in the neurons from M1/M3‐compound‐knockout mice. CCh still enhanced DSI significantly under the blockade of postsynatpic K+ conductance, and did not significantly influence the depolarization‐induced Ca2+ transients. These results indicate that the activation of postsynaptic M1 and M3 receptors facilitates the depolarization‐induced release of endocannabinoids.
Production of new cells in the rat dentate gyrus over the lifespan: relation to cognitive decline
Authors: Bizon J. L. , Gallagher M. 
Published: July 2003

AbstractThe identification of neurogenesis in the dentate gyrus of adult mammals has sparked much interest in a functional role for these new neurons in hippocampal‐dependent cognition. The current investigation used a model of age‐related cognitive decline in rodents to study the relationship between changes in markers of neurogenesis and hippocampal function. New cell production in the granule cell layer was progressively reduced across the lifespan of male Long Evans rats, with a 40% reduction at middle age (13 months) and a reduction in excess of 80% in advanced age (25 months), compared with young mature adults (7 months). These effects of aging were not, however, predictive of cognitive status. In particular, the pronounced decrease in new cell production during aging did not distinguish among rats that varied over a wide range of cognitive abilities.
7‐Hydroxylated epiandrosterone (7‐OH‐EPIA) reduces ischaemia‐induced neuronal damage both in vivo and in vitro
Authors: Pringle Ashley K. , Schmidt Werner , Deans Jackie K. , Wulfert Ernst , Reymann Klaus G. , Sundstrom Lars E. 
Published: July 2003

AbstractRecent evidence suggests that steroids such as oestradiol reduce ischaemia‐induced neurodegeneration in both in vitro and in vivo models. A cytochrome P450 enzyme termed cyp7b that 7‐hydroxylates many steroids is expressed at high levels in brain, although the role of 7‐hydroxylated steroids is unknown. We have tested the hypothesis that the steroid‐mediated neuroprotection is dependent on the formation of 7‐hydroxy metabolites. Organotypic hippocampal slice cultures were prepared from Wistar rat pups and maintained in vitro for 14 days. Cultures were then exposed to 3 h hypoxia and neuronal damage assessed 24 h later using propidium iodide fluorescence as a marker of cell damage. Neurodegeneration occurred primarily in the CA1 pyramidal cell layer. The steroids oestradiol, dehydroepiandrosterone and epiandrosterone (EPIA) were devoid of neuroprotective efficacy when present at 100 nm pre‐, during and post‐hypoxia. The 7‐hydroxy metabolites of EPIA, 7α‐OH‐EPIA and 7β‐OH‐EPIA significantly reduced neurotoxicity at 100 nm and 10 nm. 7β‐OH‐EPIA was also neuroprotective in two in vivo rat models of cerebral ischaemia: 0.1 mg/kg 7β‐OH‐EPIA significantly reduced hippocampal cell loss in a model of global forebrain ischaemia, whereas 0.03 mg/kg was neuroprotective in a model of focal ischaemia even when administration was delayed until 6 h after the onset of ischaemia. Taken together, these data demonstrate that 7‐hydroxylation of steroids confers neuroprotective efficacy, and that 7β‐OH‐epiandrosterone represents a novel class of neuroprotective compounds with potential for use in acute neurodegenerative diseases.
Human walking along a curved path. I. Body trajectory, segment orientation and the effect of vision
Authors: Courtine Grégoire , Schieppati Marco 
Published: July 2003

AbstractTask‐related characteristics of gait and segment orientation during natural locomotion along a curved path have been described in order to gain insight into the neural organization of walking. The locomotor task implied continuous deviation from straight‐ahead, thereby requiring continuous adjustment of body movement to produce and assist turn‐related torques. Performance was compared to straight‐ahead locomotion. Subjects easily reproduced both trajectories with eyes open (EO). The actual‐to‐required trajectory difference increased blindfolded (BF), more so during turning. Stride length was unchanged for the outer but decreased for the inner leg. The feet anticipated subsequent body rotation by pivoting toward the inner side of the curve at heel strike. A shift of body centre of mass and trunk roll toward the inner side accompanied turning. The head turned more than dictated by the heading change, and the absolute range of yaw oscillation increased. Head yaw anticipated body yaw by ≈ 200 ms. Despite the minor effect of vision on the behaviour of all other segments, a difference in head pitch occurred between EO and BF; with EO, the head was flexed (P < 0.01), as to look at the path, while pitch was negligible with BF. In general, the changes in the amplitude of head, trunk and feet movements proved to be well related to the kinematics of the steering body, and constituted a sort of basic library of motor synergies.
Human walking along a curved path. II. Gait features and EMG patterns
Authors: Courtine Grégoire , Schieppati Marco 
Published: July 2003

AbstractWe recorded basic gait features and associated patterns of leg muscle activity, occurring during continuous body progression when humans walked along a curved trajectory, in order to gain insight into the nervous mechanisms underlying the control of the asymmetric movements of the two legs. The same rhythm was propagated to both legs, in spite of inner and outer strides diverging in length (P < 0.001). There was a phase lag in limb displacement between the inner and outer leg of 7% of the total cycle duration (P = 0.0001). Swing velocity was greater for outer than inner foot (P < 0.001). The duration of the stance phase diminished and increased in the outer and inner leg (P < 0.01), respectively, and was associated with trunk leaning toward the inside of the path. Muscle activity was not dramatically altered during curved walking. The amplitude of soleus burst during stance increased in the outer (P < 0.05) and decreased in the inner leg (P < 0.05), without changes in timing. Tibialis anterior activity increased in both legs during the swing phase (P < 0.05); it was advanced on the outer and delayed on the inner side (P < 0.01; 2% of the cycle). The peroneus longus burst decreased in both legs, but more in the inner than the outer leg, and lasted longer in the inner leg at the onset of swing. Closing the eyes did not affect the gait pattern and muscle activity during turning. The command to walk along a curved path may exploit the basic mechanisms of the spinal locomotor generator, thereby limiting the computational cost of turning.
Meta‐ecosystems: a theoretical framework for a spatial ecosystem ecology
Authors: Loreau Michel , Mouquet Nicolas , Holt Robert D. 
Published: July 2003

AbstractThis contribution proposes the meta‐ecosystem concept as a natural extension of the metapopulation and metacommunity concepts. A meta‐ecosystem is defined as a set of ecosystems connected by spatial flows of energy, materials and organisms across ecosystem boundaries. This concept provides a powerful theoretical tool to understand the emergent properties that arise from spatial coupling of local ecosystems, such as global source–sink constraints, diversity–productivity patterns, stabilization of ecosystem processes and indirect interactions at landscape or regional scales. The meta‐ecosystem perspective thereby has the potential to integrate the perspectives of community and landscape ecology, to provide novel fundamental insights into the dynamics and functioning of ecosystems from local to global scales, and to increase our ability to predict the consequences of land‐use changes on biodiversity and the provision of ecosystem services to human societies.
Pollinators as mediators of top‐down effects on plants
Authors: Suttle Kenwyn B. 
Published: July 2003

AbstractThis paper explores the idea that predators may disrupt plant–pollinator relationships and consequently inhibit reproduction in flowering plants. Amidst growing evidence that predators influence plant–pollinator interactions, I suggest that such pollinator‐mediated indirect effects may be a common feature of terrestrial communities, with implications for research into top‐down effects and pollination ecology. Experimental evidence of such an effect from a riparian system in northern California is provided, where crab spiders decreased seed production in inflorescences of the invasive plantLeucanthemum vulgareby reducing the frequency and duration of floral visits by pollinating insects.
Biodiversity loss, trophic skew and ecosystem functioning
Authors: Duffy J. Emmett 
Published: July 2003

AbstractExperiments testing biodiversity effects on ecosystem functioning have been criticized on the basis that their random‐assembly designs do not reflect deterministic species loss in nature. Because previous studies, and their critics, have focused primarily on plants, however, it is underappreciated that the most consistent such determinism involves biased extinction of large consumers, skewing trophic structure and substantially changing conclusions about ecosystem impacts that assume changing plant diversity alone. Both demography and anthropogenic threats render large vertebrate consumers more vulnerable to extinction, on average, than plants. Importantly, species loss appears biased toward strong interactors among animals but weak interactors among plants. Accordingly, available evidence suggests that loss of a few predator species often has impacts comparable in magnitude to those stemming from a large reduction in plant diversity. Thus, the dominant impacts of biodiversity change on ecosystem functioning appear to be trophically mediated, with important implications for conservation.
The power of time: spatiotemporal scaling of species diversity
Authors: Adler Peter B. , Lauenroth William K. 
Published: July 2003

AbstractThe species–area relationship (SAR) provides the foundation for much of theoretical ecology and conservation practice. However, by ignoring time the SAR offers an incomplete model for biodiversity dynamics. We used long‐term data from permanent plots in Kansas grasslands, USA, to show that the increase in the number of species found with increasing periods of observation takes the same power‐law form as the SAR. A statistical model including time, area, and their interaction explains 98% of variation in mean species number and demonstrates that while the effect of time depends on area, and vice versa, time has strong effects on species number even at relatively broad spatial scales. Our results suggest equivalence of underlying processes in space and time and raise questions about the diversity estimates currently used by basic researchers and conservation practitioners.
Niche differentiation in Mexican birds: using point occurrences to detect ecological innovation
Authors: Peterson A. Townsend , Holt Robert D. 
Published: July 2003

AbstractThe development of quantitative models of species’ distributions has largely ignored the potential for intraspecific variation in species’ niche requirements. Application of such models may nevertheless provide a rich, untapped opportunity to address the basic issue of niche conservatism vs. evolution. We illustrate this potential using genetic algorithms coupled with geographical information systems, which provide a powerful and novel approach to characterizing species’ ecological niches and geographical distributions. Our example consists of several species of Mexican birds with recognized subspecies, and associated climatic and vegetation data. Our basic protocol is to develop an ecological niche model for each subspecies, and use this model to predict distributions of other subspecies. In some cases, the ecological niche model inferred for one subspecies provides an excellent descriptor of other subspecies’ ranges, whereas in other cases the prediction is rather poor. We suggest that the latter may reveal the potential existence of evolved, intraspecific niche differentiation. We discuss alternative, non‐evolutionary explanations, and point out potential implications of our results for predictive models of species’ invasions.
Vasopressin‐induced facilitation of adrenergic responses in the rat mesenteric artery is V1‐receptor dependent
Authors: Streefkerk J. O. , Pfaffendorf M. , Van Zwieten P. A. 
Published: July 2003

Summary1 The present study was designed to analyse the possible involvement of V1‐ and V2‐receptors in vasopressin (AVP)‐induced facilitation of the sympathetic nervous system. Furthermore, we aimed to determine whether the site of facilitation by AVP is located pre‐ or postsynaptically.2 Electrical field stimulation (EFS) was applied on the rat mesteric artery to activate the sympathetic nervous system. In addition, we evaluated the direct vascular effects of AVP. The postsynaptic effect of AVP on the sympathetic nervous system was investigated by exposing the vessels to exogenous noradrenaline. These experiments were performed in the absence or presence of selective V1and V2receptor antagonists SR 49059 and SR 121463, respectively. Desmopressin was applied as a selective V2agonist.3 The direct vasoconstrictor effect of AVP was antagonized by SR 49059 and not by SR 121463. Desmopressin neither showed any direct vasoconstrictor effect nor produced vasodilatation after a precontraction induced by noradrenaline (10 μm). The EFS‐induced rise in vascular tone could be increased by a sub‐pressor concentration of AVP. This fascilitation could be antagonized by SR 49059, but not by SR 121463. Desmopressin did not influence the increase in vascular tone during EFS. Vasoconstriction induced by exogenous noradrenaline could be facilitated by a sub‐pressor concentration of AVP and this selective postsynaptic effect could be antagonized by V1‐receptor blockade.4 In conclusion, the AVP‐induced facilitation of the sympathetic nervous system is completely V1‐receptor dependent and at least partly postsynaptically mediated.
Responsiveness, affinity constants and 2‐adrenoceptor reserves for isoprenaline on portal veins from normo‐ and pre‐ and hypertensive rats
Authors: Chen Y.‐Y. , Doggrell S. A. 
Published: July 2003

Summary 1 This study used contractility methods with the portal veins of 5‐ and 14‐week‐old Wistar–Kyoto normotensive rats (WKY) and spontaneously hypertensive rats (SHRs). The SHRs are prehypertensive at 5 weeks. 2 The first part of our study was to determine whether the responsiveness to isoprenaline and forskolin was altered in the maturation of portal veins from normo‐ and prehypertensive rats. The responses to forskolin were similar on the portal veins of 5‐ and 14‐week‐old WKY and SHRs. 3 The sensitivity and maximum responses to isoprenaline were similar on portal veins of 5‐ and 14‐week‐old WKY. The sensitivity and maximum responses to isoprenaline were lower on the portal veins of 5‐week‐old SHRs (pD2 = 8.25, maximum = 85%) than age‐matched WKY (pD2 = 8.79, maximum = 96%); these differences are not caused by hypertension. At 14 weeks, the sensitivity was similar (WKY pD2 = 8.74, SHR pD2 = 8.65) but the maximum responses to isoprenaline were lower on the portal veins SHRs (77%) than WKY (97%). Thus, the sensitivity to isoprenaline increases with the development of hypertension in the SHR portal vein. 4 The second part of the study was to determine whether the affinity for isoprenaline at β2‐adrenoceptors and the fractional β2‐adrenoceptor occupancy–response relationships on the portal vein were altered in maturation from normo‐ and pre‐hypertensive rats. The effects of bromoacetylalprenololmenthane (BAAM), an irreversible β‐adrenoceptor blocker, on the isoprenaline responses of 5‐ and 14‐week‐old WKY and SHRs were studied. Maturation of the WKY portal vein between 5 and 14 weeks was associated with a loss of affinity for isoprenaline (from pKA of 7.13 to 7.87), and increase in β2‐adrenoceptor reserve (from 72 to 92% at the 95% response). There were similar affinity and reserve findings in the maturation of the SHR portal vein. Thus, there are major changes in β2‐adrenoceptor structure and reserve in maturation on the portal vein that are irrespective of the development of hypertension.