bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of serotonin2A receptors in the d‐amphetamine‐induced release of dopamine: comparison with previous data on α1b‐adrenergic receptors
Authors: Auclair Agnès , Blanc Gérard , Glowinski Jacques , Tassin Jean‐Pol 
Published: September 2004

Abstract d‐Amphetamine is known to induce an increase in dopamine release in subcortical structures, thus inducing locomotor hyperactivity in rodents. Previous data have indicated that only 15% of the d‐amphetamine‐induced release of dopamine in the nucleus accumbens is related to locomotor activity and that this ‘functional’ dopamine release is controlled by α1b‐adrenergic receptors located in the prefrontal cortex. We show here that SR46349B (0.5 mg/kg, 30 min before d‐amphetamine), a specific serotonin2A (5‐HT2A) antagonist, can completely block 0.75 mg/kg d‐amphetamine‐induced locomotor activity without decreasing d‐amphetamine‐induced extracellular dopamine levels in the nucleus accumbens. Using the same experimental paradigm as before, i.e. a systemic injection of d‐amphetamine accompanied by a continuous local perfusion of 3 µm d‐amphetamine, we find that SR46349B (0.5 mg/kg) blocks completely the systemic (0.75 mg/kg) d‐amphetamine‐induced functional dopamine release in the nucleus accumbens. Finally, the bilateral injection of SR46349B (500 pmol/side) into the ventral tegmental area blocked both the d‐amphetamine‐induced locomotor activity and functional dopamine release in the nucleus accumbens, whereas bilateral injection of SR46349B into the medial prefrontal cortex was ineffective. We propose that 5‐HT2A and α1b‐adrenergic receptors control a common neural pathway responsible for the release of dopamine in the nucleus accumbens by psychostimulants.
Chimaerins act downstream from neurotrophins in overcoming the inhibition of neurite outgrowth produced by myelin‐associated glycoprotein
Authors: Mizuno Tatsunori , Yamashita Toshihide , Tohyama Masaya 
Published: September 2004

AbstractSeveral myelin‐derived proteins are inhibitory cues that contribute to the lack of regeneration of the CNS and inhibit neurite outgrowth from some neurons in vitro. This inhibition is blocked if neurons are exposed to neurotrophins before encountering the inhibitors. Here, we demonstrate that chimaerin, one of the Rho GTPase activating proteins, is transcriptionally up‐regulated after exposure to neurotrophins in post‐natal cerebellar neurons. The expression of α chimaerin in the cerebellum is developmentally correlated with the abolishment of the inhibitory effect of myelin‐associated glycoprotein (MAG). Ectopic expression of α chimaerin in cerebellar neurons results in resistance to MAG in regard to neurite outgrowth. These results suggest that up‐regulated expression of chimaerin counteracts the activation of RhoA, which is a key molecule in transducing inhibitory signals in neurons.
Dopamine transporter‐dependent and ‐independent actions of trace amine β‐phenylethylamine
Authors: Sotnikova Tatyana D. , Budygin Evgeny A. , Jones Sara R. , Dykstra Linda A. , Caron Marc G. , Gainetdinov Raul R. 
Published: September 2004

Abstractβ‐Phenylethylamine (β‐PEA) is an endogenous amine that is found in trace amounts in the brain. It is believed that the locomotor‐stimulating action of β‐PEA, much like amphetamine, depends on its ability to increase extracellular dopamine (DA) concentrations owing to reversal of the direction of dopamine transporter (DAT)‐mediated DA transport. β‐PEA can also bind directly to the recently identified G protein‐coupled receptors, but the physiological significance of this interaction is unclear. To assess the mechanism by which β‐PEA mediates its effects, we compared the neurochemical and behavioral effects of this amine in wild type (WT), heterozygous and ‘null’ DAT mutant mice. In microdialysis studies, β‐PEA, administered either systemically or locally via intrastriatal infusion, produced a pronounced outflow of striatal DA in WT mice whereas no increase was detected in mice lacking the DAT (DAT‐KO mice). Similarly, in fast‐scan voltammetry studies β‐PEA did not alter DA release and clearance rate in striatal slices from DAT‐KO mice. In behavioral studies β‐PEA produced a robust but transient increase in locomotor activity in WT and heterozygous mice. In DAT‐KO mice, whose locomotor activity and stereotypy are increased in a novel environment, β‐PEA (10–100 mg/kg) exerted a potent inhibitory action. At high doses, β‐PEA induced stereotypies in WT and heterozygous mice; some manifestations of stereotypy were also observed in the DAT‐KO mice. These data demonstrate that the DAT is required for the striatal DA‐releasing and hyperlocomotor actions of β‐PEA. The inhibitory action on hyperactivity and certain stereotypies induced by β‐PEA in DAT‐KO mice indicate that targets other than the DAT are responsible for these effects.
MAPK recruitment by β‐amyloid in organotypic hippocampal slice cultures depends on physical state and exposure time
Authors: Bell Karen A. , O'Riordan Kenneth J. , Sweatt J. David , Dineley Kelly T. 
Published: September 2004

AbstractElevated β‐amyloid is thought to trigger the onset of Alzheimer's disease. Alzheimer's disease is marked by progressive loss of cognitive function, an early symptom of which is episodic memory deficits. Impairment of episodic memory is linked to hippocampal pathology. We investigated the signal transduction consequences of exposure to nanomolar to low micromolar concentrations of aggregate forms of β‐amyloid in the hippocampus. We found that, in addition to activation of ERK MAPK and its downstream target ribosomal S6 kinase in hippocampal slice cultures following acute exposure to oligomeric β‐amyloid1−42, ERK activation also requires phosphoinositide‐3 kinase activity. These effects were contingent on the α7 subtype of nicotinic acetylcholine receptor. Hippocampal slice cultures treated acutely with oligomeric β‐amyloid1−42 did not exhibit JNK MAPK activation; however, chronic exposure to oligomers or high molecular weight aggregates of β‐amyloid1−42 led to JNK MAPK activation coincident with ERK MAPK down‐regulation. In contrast to the effects of acute application of oligomeric β‐amyloid1−42, nicotine activated ERK MAPK via α7 nicotinic acetylcholine receptors utilizing protein kinase A as an intermediate. In conclusion, we found that both the physical state and duration of exposure to β‐amyloid are determinants of MAPK recruitment in hippocampus. We also found that nicotine and β‐amyloid activate ERK MAPK via α7 nicotinic acetylcholine receptors but use distinct intermediate kinases. These data indicate the existence of differential coupling of α7 to downstream targets depending on the type of ligand that leads to receptor activation.
Inhibition of glutamate‐induced delayed calcium deregulation by 2‐APB and La3+ in cultured cortical neurones
Authors: Chinopoulos Christos , Gerencser Akos A. , Doczi Judit , Fiskum Gary , Adam‐Vizi Vera 
Published: September 2004

AbstractExposure of neurones in culture to excitotoxic levels of glutamate results in an initial transient spike in [Ca2+]i followed by a delayed, irreversible [Ca2+]i rise governed by rapid kinetics, with Ca2+ originating from the extracellular medium. The molecular mechanism responsible for the secondary Ca2+ rise is unknown. Here, we report that the delayed Ca2+ entry in cortical neurones is diminished by 2‐aminoethoxydiphenyl borate (2‐APB: IC50 = 62 ± 9 µm) and La3+ (IC50 = 7.2 ± 3 µm), both known to inhibit transient receptor potential (TRP) and store‐operated Ca2+ (SOC) channels. Application of thapsigargin, however, failed to exacerbate the delayed Ca2+ deregulation, arguing against a store depletion event as the stimulus for induction of the secondary [Ca2+]i rise. In addition, these neurones did not exhibit SOC entry. Unexpectedly, application of ryanodine or caffeine significantly inhibited glutamate‐induced delayed Ca2+ deregulation. In basal Ca2+ entry experiments, La3+ and 2‐APB modulated the rapid rise in [Ca2+]i caused by exposure of neurones to Ca2+ after pre‐incubating in a calcium‐free medium. This basal Ca2+ influx was mitigated by extracellular Mg2+ but not aggravated by thapsigargin, ryanodine or caffeine. These results indicate that 2‐APB and La3+ influence non‐store‐operated Ca2+ influx in cortical neurones and that this route of Ca2+ entry is involved in glutamate‐induced delayed Ca2+ deregulation.
Proteomic analysis of native metabotropic glutamate receptor 5 protein complexes reveals novel molecular constituents
Authors: Farr Carol D. , Gafken Philip R. , Norbeck Angela D. , Doneanu Catalin E. , Stapels Martha D. , Barofsky Douglas F. , Minami Manabu , Saugstad Julie A. 
Published: September 2004

AbstractWe used a proteomic approach to identify novel proteins that may regulate metabotropic glutamate receptor 5 (mGluR5) responses by direct or indirect protein interactions. This approach does not rely on the heterologous expression of proteins and offers the advantage of identifying protein interactions in a native environment. The mGluR5 protein was immunoprecipitated from rat brain lysates; co‐immunoprecipitating proteins were analyzed by mass spectrometry and identified peptides were matched to protein databases to determine the correlating parent proteins. This proteomic approach revealed the interaction of mGluR5 with known regulatory proteins, as well as novel proteins that reflect previously unidentified molecular constituents of the mGluR5‐signaling complex. Immunoblot analysis confirmed the interaction of high confidence proteins, such as phosphofurin acidic cluster sorting protein 1, microtubule‐associated protein 2a and dynamin 1, as mGluR5‐interacting proteins. These studies show that a proteomic approach can be used to identify candidate interacting proteins. This approach may be particularly useful for neurobiology applications where distinct protein interactions within a signaling complex can dramatically alter the outcome of the response to neurotransmitter release, or the disruption of normal protein interactions can lead to severe neurological and psychiatric disorders.
A novel constitutively active mutation in the second cytoplasmic loop of metabotropic glutamate receptor
Authors: Yamashita Takahiro , Kai Toshihiro , Terakita Akihisa , Shichida Yoshinori 
Published: September 2004

AbstractG protein‐coupled receptors have a common structural motif of seven transmembrane α‐helices and are classified into different families showing no sequence similarity. Extensive studies have been conducted on the structure–function relationship in family 1 receptors, but those in other families have not been well studied. In this study, to investigate the molecular basis leading to the G protein activation by metabotropic glutamate receptor (mGluR), the member of family 3, we searched for the amino acid residues responsible for the G protein activation in the second cytoplasmic loop, which was thought to be the main G protein binding region. Analyses of the systematical mutations of Gi/Go‐coupled mGluR8 revealed the presence of a constitutively active mutation in the C‐terminal region of the second loop. The corresponding mutation in the second loop of Gq‐coupled mGluR1 also exhibited high agonist‐independent activity. These results indicate that there is a common constitutive active mutation site regardless of mGluR subtypes, suggesting that the structural change of the junction between the second cytoplasmic loop and helix IV is strongly linked to the formation of the active state.
Evidence for histamine as a transmitter in rat carotid body sensor cells
Authors: Koerner Pia , Hesslinger Christian , Schaefermeyer Agnes , Prinz Christian , Gratzl Manfred 
Published: September 2004

AbstractCarotid bodies harboring sensor cells for oxygen have a strategic location at the bifurcation of the carotid artery, which supplies the brain. Upon arterial hypoxia they transmit signals to the respiratory center, which increases the frequency of breathing. Dopamine is considered as the predominant transmitter of the rat carotid body sensor cells. Here we show that the rat carotid body sensor cells are the first cell type known to have the complete apparatus to synthesize, store and release both dopamine and histamine. The tyrosine hydroxylase positive dopaminergic sensor cells of juvenile rats express the histamine biosynthesis enzyme, histidine decarboxylase. Moreover, the sensor cells have not only vesicular monoamine transporter 1 (VMAT1) transporting catecholamines but also VMAT2, which is highly specific for histamine. Additionally, we found that these cells possess components of the neuroendocrine exocytosis apparatus, synaptosome‐associated protein of 25 kDa (SNAP 25) and syntaxin1. The amount of histamine determined in the rat carotid body (164 pmol/carotid body) is more than 10‐fold higher compared with that of dopamine. As a main effect, hypoxia significantly increased histamine release from isolated rat carotid bodies as it has been shown for dopamine. Finally, RT‐PCR experiments indicate the presence of histamine receptors H1, H2 and H3 in the carotid body. Our data suggest that histamine is synthesized, stored and released upon hypoxia by dopaminergic sensor cells of the rat carotid body.
The reproductive biology of the White‐necked PicathartesPicathartes gymnocephalus
Authors: Thompson Hazell Shokellu 
Published: September 2004

The reproductive biology of the White‐necked PicathartesPicathartes gymnocephalus, a threatened species endemic to the Upper Guinea rainforest of West Africa, was studied in Sierra Leone from 1990 to 1996. The modal clutch size was two (mean 1.92) eggs. Incubation averaged 20 days and the nestling period 25 days. Nesting success (probability of eggs laid surviving to fledge) was 22.9%. Only 0.44 chicks fledged per nesting pair. The main known causes of nest mortality were predation and infanticide. Nestlings fledged when almost 30% smaller than adult size. A life‐table indicates that populations in Sierra Leone could be declining slowly. Alternatively, White‐necked Picathartes could be very long‐lived (annual adult survival could be greater than 90%), in which case populations would be self‐sustaining.
Environmental heterogeneity, spatial segregation of prey, and the utilization of southwest Atlantic mudflats by migratory shorebirds
Authors: Ribeiro Pablo D. , Iribarne Oscar O. , Navarro Diego , Jaureguy Luciano 
Published: September 2004

We studied the relationships between the habitat use of migratory shorebirds and the spatial distributions of the Southwestern Atlantic Fiddler Crab Uca uruguayensis, polychaetes, sediment characteristics and tidal levels in the Río de La Plata estuary, Argentina, where U. uruguayensis is one of the most important intertidal species. Crabs have a well‐defined patchy distribution that is segregated spatially from that of polychaetes. Crab density on the surface varied across the tidal cycle, reaching maximum values during low tide. Polychaete density decreased with depth but showed no change through the tidal cycle; however, given that sediment penetrability did change during the same period, their availability to probing shorebirds is expected to change. Habitat use by shorebirds followed the spatial distribution of prey; shorebirds that foraged on polychaetes (White‐rumped Sandpiper Calidris fuscicollis, Two‐banded Plover Charadrius falklandicus and Hudsonian Godwit Limosa haemastica) focused their attention on the areas with the highest densities of polychaetes, whereas species that preyed mostly on crabs (Ruddy Turnstone Arenaria interpres, Whimbrel Numenius phaeopus and Grey Plover Pluvialis squatarola) predominantly used areas with crabs. This segregation occurred particularly during low tide, a period in which polychaetes became fully available. Results show that the spatial and temporal heterogeneity of mudflats in relation to the types and availability of prey has a strong effect on shorebird habitat use.
Predicting the effects of marine climate change on the invertebrate prey of the birds of rocky shores
Authors: Kendall Michael A. , Burrows Michael T. , Southward Alan J. , Hawkins Stephen J. 
Published: September 2004

By the end of the 21st century models of climate change predict that the air temperature over most of the British Isles will increase by between 2 and 3 °C and sea‐level will rise by 40–50 cm. Over that period it will become windier and mean wave height will increase, as will the frequency of storms. These changes in climate and weather will impact the intertidal zone of the UK and will cause distribution changes in many of the common invertebrate species that live there. Where these changes are severe they may well impact on patterns of distribution of ducks and wading birds. In the British Isles a number of organisms live close to their geographical limits of distribution. Some of these species might be expected to extend their range as climatic restraints are relaxed. Species currently limited by cool summers or winter cold will move northwards. In most cases the effects on the distribution of waterbirds will be small. For example, the replacement of the Northern Limpet Patella vulgata by the Southern Limpet P. depressa is unlikely to adversely affect Eurasian Oystercatchers Haematopus ostralegus. Of wider concern is the possibility that as climate warms the abundance and productivity of brown algae will decrease. This is likely to have two significant effects for waders. First, it would represent a loss of potentially rich feeding grounds for species such as Ruddy Turnstone Arenaria interpres that feed on small easily desiccated invertebrates living on or below the seaweed. Secondly, as algae die or are broken away the resulting debris is exported to sediment habitats where it considerably boosts the in situ production of bacteria at the base of the food web. An increase in sea‐level will only have a major impact on the extent of rocky shore invertebrate communities where shore topography prevents the upward migration of the biota. Where a seawall limits shores, for example, biological production will be curtailed as the area available for colonization decreases. Increases in the size of waves and the frequency of storms will mimic increasing exposure and there will be a significant reduction in algal production in areas that are affected.
The recent declines of farmland bird populations in Britain: an appraisal of causal factors and conservation actions
Authors: Newton Ian 
Published: September 2004

In this paper, the main aspects of agricultural intensification that have led to population declines in farmland birds over the past 50 years are reviewed, together with the current state of knowledge, and the effects of recent conservation actions. For each of 30 declining species, attention is focused on: (1) the external causes of population declines, (2) the demographic mechanisms and (3) experimental tests of proposed external causal factors, together with the outcome of (4) specific conservation measures and (5) agri‐environment schemes. Although each species has responded individually to particular aspects of agricultural change, certain groups of species share common causal factors. For example, declines in the population levels of seed‐eating birds have been driven primarily by herbicide use and the switch from spring‐sown to autumn‐sown cereals, both of which have massively reduced the food supplies of these birds. Their population declines have been associated with reduced survival rates and, in some species, also with reduced reproductive rates. In waders of damp grassland, population declines have been driven mainly by land drainage and the associated intensification of grassland management. This has led to reduced reproductive success, as a result of lowered food availability, together with increased disturbance and trampling by farm stock, and in some localities increased nest predation. The external causal factors of population decline are known (with varying degrees of certainty) for all 30 species considered, and the demographic causal factors are known (again with varying degrees of certainty) for 24 such species. In at least 19 species, proposed causal factors have been tested and confirmed by experiment or by local conservation action, and 12 species have been shown to benefit (in terms of locally increased breeding density) from options available in one or more agri‐environment schemes. Four aspects of agricultural change have been the main drivers of bird population declines, each affecting a wide range of species, namely: (1) weed‐control, mainly through herbicide use; (2) the change from spring‐sown to autumn‐sown cereal varieties, and the associated earlier ploughing of stubbles and earlier crop growth; (3) land drainage and associated intensification of grassland management; and (4) increased stocking densities, mainly of cattle in the lowlands and sheep in the uplands. These changes have reduced the amounts of habitat and/or food available to many species. Other changes, such as the removal of hedgerows and ‘rough patches’, have affected smaller numbers of species, as have changes in the timings of cultivations and harvests. Although at least eight species have shown recent increases in their national population levels, many others seem set to continue declining, or to remain at a much reduced level, unless some relevant aspect of agricultural practice is changed.
Detection and Management of Cognitive Impairment in Primary Care: The Steel Valley Seniors Survey
Authors: Ganguli Mary , Rodriguez Eric , Mulsant Benoit , Richards Stephanie , Pandav Rajesh , Bilt Joni Vander , Dodge Hiroko H. , Stoehr Gary P. , Saxton Judith , Morycz Richard K. , Rubin Robert T. , Farkas Barry , DeKosky Steven T. 
Published: September 2004

Objectives: To identify characteristics of older primary care patients who were cognitively impaired and who underwent mental status testing by their physicians.Design: Cross‐sectional and retrospective analysis.Setting: Seven small‐town primary care practices.Participants: A total of 1,107 patients with a mean±standard deviation age of 76.3±6.6, screened using the Mini‐Mental State Examination (MMSE); medical records reviewed.Measurements: Demographics, MMSE, medical record information. Odds ratios (OR) with 95% confidence intervals (CI), adjusted for age, sex, and education.Results: Thirty‐one percent of the sample had MMSE scores of less than 25. Among these patients, physicians documented memory loss in only 23% which was significantly more often than in the higher scoring group (OR=1.9, 95% CI=1.3–2.8), basic activity of daily living (ADL) impairment in 7.9% (OR=2.4, 95% CI=1.3–4.4), instrumental ADL (IADL) impairment in 6.7% (OR=2.2, 95% CI=1.1=4.2), dementia in 12.2% (OR=3.7, 95% CI=2.0–6.8), and prescription of cholinesterase inhibitors in 7.6% (OR=4.4, 95% CI=1.9–10.2). Physicians recorded mental status testing largely in patients with research MMSE scores of 24 to 28, significantly more often when they also documented memory loss (OR=3.8, 95% CI=2.5–5.6) or impaired IADLs (OR=2.7, 95% CI=1.4–5.2), diagnosed dementia (OR=4.9, 95% CI=2.8–8.6), referred to specialists (OR=6.3, 95% CI=2.5–16.2) or social services (OR=3.6, 95% CI=1.8–7.3), or prescribed cholinesterase inhibitors (OR=8.5, 95% CI=4.2–17.5).Conclusion: Physicians noted impairment in a minority of impaired patients. They tested mental status in those with documented cognitive and functional difficulties, in very mildly impaired patients, and in those for whom they intervened.