bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduced anxiety and improved stress coping ability in mice lacking NPY‐Y2 receptors
Authors: Tschenett Alexandra , Singewald Nicolas , Carli Mirjana , Balducci Claudia , Salchner Peter , Vezzani Annamaria , Herzog Herbert , Sperk Günther 
Published: July 2003

AbstractNeuropeptide Y (NPY) has been implicated in the pathophysiology of certain mood disorders, including depression and anxiety. It is, however, not known which of the five cloned NPY receptors mediate these functions. We investigated the effect of Y2 receptor deletion on anxiety and stress‐related behaviours. In the elevated plus maze, Y2 knock out (Y2−/−) mice showed a 2.7‐fold higher frequency of entering into, and spent 3.8 times more time within, the open arms compared to controls, while entries into the closed arms did not differ. Similarly Y2−/− mice entered the central area of the open field 1.7 times more frequently and also spent 1.8 times more time there. In the light/dark test Y2−/− mice had a 4.8‐fold lower latency to enter the lit area but stayed there 2.6 times longer than control mice. Y2−/− mice displayed 3.2‐fold less immobility in the forced swim test, indicating improved stress coping ability. Y2 receptors are predominantly located presynaptically where they mediate feedback inhibition of neurotransmitter release. Deletion of these receptors may result in enhanced release of NPY, GABA and/or glutamate in brain areas linked to the manifestation of anxiety, and stress‐related behaviour such as the amygdala. Taken together, deletion of the Y2 receptor has revealed an important role of Y2 receptors in the generation of anxiety‐related and stress‐related behaviours in mice.
The ablation of glial fibrillary acidic protein‐positive cells from the adult central nervous system results in the loss of forebrain neural stem cells but not retinal stem cells
Authors: Morshead Cindi M. , Garcia A. Denize , Sofroniew Michael V. , Van Der Kooy Derek 
Published: July 2003

AbstractThe adult mammalian forebrain subependyma contains neural stem cells (NSCs) capable of self‐renewal and multilineage differentiation. The in vivo identification of NSCs has not been definitively addressed using a loss of function approach. Using a transgenic mouse expressing herpes‐simplex virus thymidine kinase from the glial fibrillary acidic protein (GFAP) promotor, we have selectively killed dividing GFAP‐positive cells in the presence of ganciclovir (GCV) and shown a > 95% loss in the numbers of NSCs, as assayed by the formation of clonally derived neurospheres in vitro. This loss is seen following 3 days of GCV exposure in vivo or in vitro only and cannot be rescued by coculturing with pure astrocyte populations or control (green fluorescent protein‐expressing) subependymal cells. Exposure to GCV in vitro has no effect on adult retinal stem cells hence, we conclude that adult forebrain NSCs comprise a subpopulation of the GFAP‐positive cells within the subependyma.
Brain capillaries and cholinergic neurons persist in organotypic brain slices in the absence of blood flow
Authors: Moser Karma V. , Schmidt‐Kastner Rainald , Hinterhuber Hartmann , Humpel Christian 
Published: July 2003

AbstractAngiogenesis plays an important role during development of the brain and under pathological conditions. The aim of the present study was to observe interaction of brain capillaries and cholinergic neurons in organotypic brain slices. Immunohistochemistry was used to visualize brain capillary‐like structures (RECA‐1 antigen) and cholinergic neurons (choline acetyltransferase). Under normal culture conditions, a very low number of brain capillaries was found in 2‐ and 4‐week‐old cortex brain slices. Treatment of slices with acidic medium (pH 6) or hyperthermia (42 °C) markedly enhanced the number of brain capillaries. Incubation with 10 ng/mL vascular endothelial growth factor only enhanced angiogenesis in more developed slices. Cholinergic neurons survived in slices of the basal nucleus of Meynert; however, hyperthermia but not acidosis markedly decreased their number. In coslices of the basal nucleus of Meynert and cortex (pretreated with acidic medium), a high number of RECA‐1‐positive capillaries and cholinergic neurons persisted and displayed strong nerve fibre growth of cholinergic fibres into the cortex. In conclusion, we have demonstrated that RECA‐1‐positive capillaries and cholinergic neurons can be studied in slice cultures in the absence of blood perfusion, and that this model could provide a system to study mechanisms involved in vascular dementia.
Regional differences in the circadian modulation of human sleep spindle characteristics
Authors: Knoblauch Vera , Martens Wim , Wirz‐Justice Anna , Kräuchi Kurt , Cajochen Christian 
Published: July 2003

AbstractElectroencephalographic oscillations in the sleep spindle frequency range (11–16 Hz) are a key element of human nonrapid eye movement sleep. In the present study, sleep spindle characteristics along the anterior–posterior axis were analysed during and outside the circadian phase of melatonin secretion. Sleep electroencephalograms were recorded during naps distributed over the entire circadian cycle and analysed with two different methodological approaches, the classical fast Fourier transform in the frequency‐domain and a new method for instantaneous spectral analysis, the fast time frequency transform that yields high‐resolution parameters in the combined time‐frequency‐domain. During the phase of melatonin secretion, spindle density was generally increased and intraspindle frequency variation reduced. Furthermore, lower spindle frequencies were promoted: peak frequencies shifted towards the lower end of the spindle frequency range, and spindle amplitude was enhanced in the low‐frequency range (11–14.25 Hz) and reduced in the high‐frequency range (∼14.5–16 Hz). The circadian variation showed a clear dependence on brain topography such that it was maximal in the parietal and minimal in the frontal derivation. Our data provide evidence that the circadian pacemaker actively promotes low‐frequency sleep spindles during the biological night with a parietal predominance.
Olfactory input to the parahippocampal region of the isolated guinea pig brain reveals weak entorhinal‐to‐perirhinal interactions
Authors: Biella G. R. , Gnatkovsky V. , Takashima I. , Kajiwara R. , Iijima T. , De Curtis M. 
Published: July 2003

AbstractThe processing of olfactory inputs by the parahippocampal region has a central role in the organization of memory in mammals. The olfactory input is relayed to the hippocampus via interposed synapses located in the piriform and entorhinal cortices. Whether olfactory afferents directly or indirectly project to other areas of the parahippocampal region beside the entorhinal cortex (EC) is uncertain. We performed an electrophysiological and imaging study of the propagation pattern of the olfactory input carried by the fibres that form the lateral olfactory tract (LOT) into the parahippocampal region of the in vitro isolated guinea pig preparation. Laminar analysis was performed on field potential depth profiles recorded with 16‐channel silicon probes at different sites of the insular–parahippocampal cortex. The LOT input induced a large amplitude polysynaptic response in the lateral EC. Following appropriate LOT stimulation, a late response generated by the interposed activation of the hippocampus was observed in the medial EC. LOT stimulation did not induce any local response in area 36 of the perirhinal cortex (PRC), while a small amplitude potential with a delay similar to the lateral EC response was inconsistently observed in PRC area 35. No PRC potentials were observed following the responses evoked by LOT stimulation in either the lateral or the medial EC. These findings were substantiated by current source density analysis of PRC laminar profiles. To further verify the absence of EC‐to–PRC field interactions after LOT stimulation, high‐resolution optical imaging of neuronal activity was performed after perfusion of the isolated brain with the voltage‐sensitive dye RH‐795. The optical recordings confirmed that olfactory‐induced activity in the EC does not induce massive PRC activation. The present findings suggest that the olfactory input into the parahippocampal region is confined to the entorhinal cortex. The results also imply that, as demonstrated for the PRC‐to‐EC pathway, the propagation of neuronal activity from the EC to the PRC is hindered, possibly by a powerful inhibitory control generated within the EC.
Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus
Authors: Von Gall Charlotte , Noton Elizabeth , Lee Choogon , Weaver David R. 
Published: July 2003

AbstractBiological rhythms in mammals are driven by a central circadian clock located in the suprachiasmatic nucleus (SCN). At the molecular level the biological clock is based on the rhythmic expression of clock genes. Two basic helix–loop–helix (bHLH)/PAS‐containing transcription factors, CLOCK and BMAL1 (MOP3), provide the basic drive to the system by activating transcription of negative regulators through E box enhancer elements. A critical feature of circadian timing is the ability of the clockwork to be entrained to the environmental light/dark cycle. The light‐resetting mechanism of the mammalian circadian clock is poorly understood. Light‐induced phase shifts are correlated with the induction of the clock genes mPer1 and mPer2 and a subsequent increase in mPER1 protein levels. It has previously been suggested that rapid degradation of BMAL1 protein in the rat SCN is part of the resetting mechanism of the central pacemaker. Our study shows that BMAL1 and CLOCK proteins are continuously expressed at high levels in the mouse SCN, supporting the hypothesis that rhythmic negative feedback plays the major role in rhythm generation in the mammalian pacemaker. Using both immunocytochemistry and immunoblot analysis, our studies demonstrate that BMAL1 protein in the mouse SCN is not affected by a phase‐resetting light pulse. These results indicate that rapid degradation of BMAL1 protein is not a consistent feature of resetting mechanisms in rodents.
Induction of rapid, activity‐dependent neuronal–glial remodelling in the adult rat hypothalamus in vitro
Authors: Langle Sarah L. , Poulain Dominique A. , Theodosis Dionysia T. 
Published: July 2003

AbstractThe hypothalamic oxytocinergic system offers a remarkable model of morphological plasticity in the adult because its neurons and astrocytes undergo mutual remodelling in relation to differing physiological conditions. Among various factors involved in such plasticity, oxytocin (OT) itself appears of primary importance as its central administration resulted in morphological changes similar to those brought on by physiological stimuli. In the present study, we applied OT on acute hypothalamic slices from adult rats that included the supraoptic nucleus. Using ultrastructural morphometric analyses, we found that it induced a significant reduction of astrocytic coverage of OT neurons, leaving their surfaces directly juxtaposed, to an extent similar to that detected in vivo under conditions like lactation. These neuronal–glial changes were rapid and reversible, occurring within a few hours, and specifically mediated via OT receptors. They were potentiated by oestrogen and depended on calcium mobilization and de novo protein synthesis. Moreover, they depended on concurrent neuronal activation brought on by hyperosmotic stimulation or blockade of inhibitory GABAergic neurotransmission; they were inhibited by blockade of glutamatergic receptors. Taken together, our observations show that intrahypothalamic release of OT affects not only neuronal activation of the OT system but its morphological plasticity as well. Moreover, the activity dependence of the OT‐induced changes strongly suggests that astrocytes can sense the level of activity of adjacent neurons and/or afferent input and this can subsequently act as a signal to bring on the neuronal and glial conformational changes.
Rilmenidine produces mydriasis in cats by stimulation of CNS α2‐adrenoceptors
Authors: Koss M. C. 
Published: July 2003

Summary 1
Experiments were undertaken to determine if the imidazoline/α2‐adrenoceptor agonist, rilmenidine, would produce mydriasis in cats and, if so, to delineate its site of action and determine if this effect is mediated by imidazoline receptors or α2‐adrenoceptors. 2 Rilmenidine produced dose‐related pupillary dilator responses in pentobarbital anaesthetized cats that were independent of sympathetic innervation to the iris but were dependent upon intact parasympathetic neuronal tone. The ED50 for rilmenidine‐induced pupillary dilation was approximately 200 μg kg−1, i.v., and was sustained for at least 1 h. 3 The highly selective α2‐adrenoceptor antagonist, RS‐79948, administered either before or after rilmenidine, antagonized rilmenidine‐induced mydriasis. Neuronally induced reflex inhibition of parasympathetic nerve activity was also inhibited by administration of RS‐79948. 4 These results suggest that rilmenidine acts like clonidine to produce pupillary dilation by inhibition of parasympathetic tone to the iris sphincter and that this central nervous system parasympatho‐inhibition is mediated by α2‐adrenoceptors, rather than imidazoline receptors.
Actions of domperidone on the opioid system in isolated guinea‐pig ileum: differences between dopamine antagonists on opioid system
Authors: Ozaki M. , Masuda Y. , Kishioka S. , Yamamoto H. 
Published: July 2003

Summary

To validate the relationship between the dopaminergic, opioidergic and cholinergic nervous systems, we evaluated the effect of domperidone, a dopamine (D2) antagonist, on the opioid system in myenteric plexus‐longitudinal muscle preparation isolated from the guinea‐pig ileum.
One micromolar of domperidone did not affect the 0.1 Hz‐evoked (duration 0.5 ms, maximum intensity) twitch response, but concentration dependently inhibited the twitch response between concentrations of 2 and 20 μm, and the inhibition was maximum after 20–30 min at the highest concentration used (20 μm).
Acetylcholine‐evoked contraction on basal tension was also not inhibited by 1 μm domperidone, but the contraction was concentration dependently inhibited at concentrations of 10–100 μm in a non‐competitive manner.
One micromolar of domperidone, however, increased post‐tetanic twitch inhibition, an indicator of the release of endogenous opioids. This increase was completely antagonized by 1 μm naloxone.
Twitch inhibition induced by dynorphin 1–13 (0.1–10 nm) was not affected by 1 μm domperidone, but increased the maximum twitch inhibition caused by morphine (0.1–1 μm).
These results might reflect the existence of an interaction between the dopaminergic and opioidergic system without the inhibition of the cholinergic system. Dopamine antagonists increased opioid action, an action that may depend more on the increased release of endogenous opioids than on supersensitivity of the opioid receptor.
Reflex bradycardia induced by hydralazine in sino‐aortic deafferented conscious rats
Authors: Sánchez‐Salvatori M. A. , Vidrio H. 
Published: July 2003

Summary 1 It is generally recognized that the vasodilator hydralazine produces hypotension accompanied by baroreflex‐mediated tachycardia. In some experimental conditions, however, the accompanying heart rate change is bradycardia, a paradoxical response which has not been satisfactorily explained. The present study examined the possibility of hydralazine‐induced bradycardia being mediated by vagal or sympathetic afferents activated by changes in left ventricular pressure. 2 Systolic blood pressure and heart rate responses to hydralazine were recorded in conscious normotensive intact rats by a tail cuff method and compared with responses in animals subjected to previous sino‐aortic deafferentation (SAD) to remove the influence of the arterial baroreflex. Responses were also obtained after blockade of myocardial afferent vagal C‐fibres with urethane, of efferent vagal impulses to the heart with methylatropine, of positive inotropic effects of hydralazine with atenolol, and of prostanoid sensitization of myocardial nerve fibres with indomethacin. 3 Hydralazine produced hypotension and tachycardia in intact rats, and hypotension and bradycardia in SAD animals. In intact rats, this pattern was not affected by any of the pretreatments, while in SAD rats, all pretreatments reversed the bradycardia to hydralazine. 4 The present results indicate that suppression of the arterial baroreflex by SAD propitiates the appearance of a bradycardiac response to hydralazine. This reaction probably results from activation of a vagal cardiodepressant reflex originating in the heart, as suggested by its blockade by drugs acting at various sites along the reflex arch.
Increased blocking activity of combined tachykinin NK1‐ and NK2‐receptor antagonists on tachykinergic bronchomotor responses in the guinea‐pig
Authors: Corboz M. R. , Fernandez X. , Rizzo C. A. , Tozzi S. , Monahan M. E. , Hey J. A. 
Published: July 2003

Summary 1 The present study compared the effect of the administration of tachykinin NK1‐ and NK2‐receptor antagonists alone and in combination on exogenous and endogenous tachykinin‐induced contractions using three different guinea‐pig airway preparations: isolated bronchus, isolated perfused lung and in vivo. 2 In the isolated bronchi, the tachykinin NK1‐receptor antagonist CP 99994 (0.01–1 μm)produced concentration‐dependent inhibition of contractions induced the tachykinin NK1‐receptor agonists substance P (SP) and [Met‐OMe11] SP ([Met‐OMe11]SP), whereas the tachykinin NK2‐receptor antagonist SR 48968 (0.1 μm) had no effect. SR 48968 (0.001–0.01 μm)concentration‐dependently inhibited contractions induced by the tachykinin NK2‐receptor agonists neurokinin A (NKA) and [β‐Ala8]‐neurokinin A (4–10) ([βAla8]‐NKA) whereas CP 99994 (0.1 μm) did not inhibit the contractions. The contractile activity of capsaicin, an agent that releases endogenous tachykinins from sensory C‐fibres, was inhibited in a concentration dependent manner by SR 48968 (0.001–0.03 μm) but not by CP 99994 (0.1 μm). Combination of CP 99994 and SR 48968 caused increased inhibitory effects on the concentration–response curves to SP, [Met‐OMe11]SP, NKA, [β‐Ala8]‐NKA and capsaicin. 3 In isolated perfused lungs, SR 48968 concentration (0.01–10 μm) dependently inhibited NKA‐, [β‐Ala8]‐NKA‐ and capsaicin‐induced bronchoconstriction whereas CP 99994 (30 μm) had no effect on SP‐, NKA‐, [β‐Ala8]‐NKA‐ and capsaicin‐induced bronchoconstriction. Combination of inactive concentrations of CP 99994 and SR 48968 produced an increased inhibitory effect on all previous stimuli‐induced bronchoconstriction. 4 In in vivo guinea‐pig studies, intravenous and oral pretreatment with SR 48968 (0.01–1 mg kg−1 i.v. and 0.1–3 mg kg−1 p.o., respectively), but not with CP 99994 (1 mg kg−1 i.v. and 0.3–30 mg kg−1 p.o., respectively), produced a dose‐dependent inhibition of the bronchoconstrictor responses induced by NKA, [β‐Ala8]‐NKA and capsaicin. CP 99994 intravenously (0.3 mg kg−1) and orally (3–10 mg kg−1) inhibited SP‐induced bronchoconstriction only. Intravenous and oral low dose combinations of CP 99994 and SR 48968 produced an increased inhibition of SP‐, NKA‐, [β‐Ala8]‐NKA‐ and capsaicin‐induced bronchoconstriction, respectively. 5 The present data indicate that combined tachykinin NK1‐ and NK2‐receptor antagonist treatment compared with single antagonist treatment, using CP 99994 and SR 48968, produced an augmented blockade of tachykinin NK1‐, NK2‐ and capsaicin‐mediated contractions in guinea pig airways. These findings support the hypothesis that a dual NK1‐ and NK2‐receptor antagonist may provide an advantage over single activity tachykinin NK1‐ or NK2‐receptor antagonists in pulmonary obstructive diseases.
The effect of chronic ethanol administration on nitric oxide‐mediated responses in rat isolated trachea preparation
Authors: Usta C. , Şadan G. 
Published: July 2003

Summary 1 In the present study, we investigated the effect of chronic ethanol administration on nitric oxide (NO)‐mediated responses in rat isolated trachea preparation. 2 Ethanol was given to rats in a modified liquid diet for 21 days. Isolated tracheal rings were then used to obtain responses to electrical field stimulation (EFS) after precontraction with 100 μm histamine. The parameters of field stimulation were as follows: supramaximal voltage of 50 V, 0.5 ms duration, 10‐s train; 0.5, 1, 3, 5, 10, 20, 30 and 50 Hz at 2‐min intervals. The effects of l‐and d‐arginine (10−6 m) on the responses to field stimulation (10–20 Hz) were studied. In other experiments, we tested the effects of Nω‐nitro‐l‐arginine methyl ester (l‐NAME, 10−6–10−5 m) and SIN‐1 (10−6–10−5 m) on the responses to field stimulation. 3 Electrical field stimulation induced relaxation responses in the tracheal rings precontracted with histamine from control‐ and ethanol‐treated rats. The relaxation responses induced by EFS were significantly reduced in the tracheal rings precontracted with histamine from ethanol dependent group. The responses induced by EFS in both groups were completely abolished by tetrodotoxin (1 μm), but unaffected by hexamethonium (1 μm). Incubation with d‐arginine did not cause statistically significant increases in relaxation responses to EFS in both groups. l‐Arginine (10−6 m) caused statistically significant increases in relaxation responses to EFS in control rats, but not in ethanol dependent rats. Incubation with l‐NAME (10−6–10−5 m) caused statistically significant inhibition of the relaxation responses to EFS in both groups. SIN‐1 (10−6–10−5 m) induced significantly increase in relaxation responses to EFS in both groups. 4 Our results suggest that the possible mechanism responsible for inhibition of tracheal inhibitory responses to EFS in ethanol‐dependent rats may be a reduction in production of NO and in the uptake of l‐arginine.
Inhibition of calcium/calmodulin‐dependent protein kinase II normalizes diabetes‐induced abnormal vascular reactivity in the rat perfused mesenteric vascular bed
Authors: Yousif M. H. M. , Benter I. F. , Akhtar S. 
Published: July 2003

Summary 1 Calcium/calmodulin‐dependent protein kinase II (CaMKII) has an important function in mediating insulin release but its role in the development of diabetes‐induced cardiovascular complications is not known. 2 We investigated the ability of a chronic administration of KN‐93 (5 mg kg−1alt diem for 4 weeks), an inhibitor of CaMKII, to modulate the altered vasoreactivity of the perfused mesenteric bed to common vasoconstrictors and vasodilators in streptozotocin (STZ)‐induced diabetes. 3 The vasoconstrictor responses induced by noradrenaline (NE), endothelin‐1 (ET‐1), and angiotensin II (Ang II), were significantly increased whereas, vasodilator responses to carbachol and histamine were significantly reduced in the perfused mesenteric bed of the STZ‐diabetic rats as compared with non‐diabetic controls. 4 Inhibition of CaMKII by KN‐93 treatment did not affect blood glucose levels but produced a significant normalization of the altered agonist‐induced vasoconstrictor and vasodilator responses. KN‐93 did not affect agonist‐induced responses in control animals. In addition, KN‐93 significantly reduced weight loss in diabetic rats. 5 The present data suggest that CaMKII is an essential mediator in the development of diabetic vascular dysfunction and may also play an important role in signalling pathways leading to weight loss during diabetes.