bluuebunny/crossref_metadata_2025_split huggingface dataset:
The anxiolytic effect of the CRH1 receptor antagonist R121919 depends on innate emotionality in rats
Authors: Keck Martin E. , Welt Tobias , Wigger Alexandra , Renner Ulrich , Engelmann Mario , Holsboer Florian , Landgraf Rainer 
Published: March 2003

AbstractHyperactivity of central corticotropin‐releasing hormone (CRH) circuits appears to contribute to the symptomatology of affective and anxiety disorders and therefore CRH receptor antagonists have attracted attention as potential therapeutic agents. R121919, a novel high‐affinity nonpeptide CRH1 receptor antagonist, displaced 125I‐oCRH in rat pituitary, cortex and amygdala, but not in choroid plexus or cerebral blood vessels in vitro and in vivo, which is consistent with CRH1 receptor antagonism. In vivo, R121919 significantly inhibited stress‐induced corticotropin release in rats selectively bred for high‐ and low‐anxiety‐related behaviour but displayed anxiolytic effects in high‐anxiety rats only. These data, corroborated by ex vivo receptor occupancy studies, suggest that this animal model is appropriate for the evaluation of CRH1 receptor antagonists and that compounds such as R121919 will be beneficial whenever the central stress hormone system is hyperactive.
Characterization of the metabotropic glutamate receptors mediating phospholipase C activation and calcium release in cerebellar granule cells: calcium‐dependence of the phospholipase C response
Authors: Masgrau Roser , Servitja Joan‐Marc , Young Kenneth W. , Pardo Raul , Sarri Elisabet , Nahorski Stefan R. , Picatoste Fernando 
Published: March 2003

AbstractIn this study we have determined the metabotropic glutamate receptors (mGluRs) involved in the glutamate activation of phospholipase C (PLC) and Ca2+ mobilization in cerebellar granule cells at 9 days in vitro; and studied the Ca2+ modulation of the PLC response. Both PLC activation and Ca2+ signalling were found to be mediated exclusively by the mGluR1 subtype, although both group I mGluRs, mGluR1α and mGluR5, could be detected in cell extracts. Exposure of cells to medium devoid of Ca2+ for various times before agonist stimulation reduced the PLC response, which was quickly recovered following the re‐exposure of cells to Ca2+‐containing medium. The extent of the glutamate response correlated well with changes in the cytosolic Ca2+ concentration. On the other hand, loading of the intracellular Ca2+ stores by a transient depolarization followed by washing in nondepolarizing buffer, allowed glutamate to release stored Ca2+ in the majority of cells and enhanced glutamate activation of PLC. Under such conditions, the absence of extracellular Ca2+ during stimulation and the chelation of cytosolic Ca2+ with BAPTA/AM inhibited both glutamate‐elicited Ca2+ response and PLC activation. Overall, these results indicate that the mGluR‐mediated activation of PLC depends on the presence of extracellular Ca2+ and can be modulated by moderate changes of cytosolic Ca2+. Furthermore, ryanodine reduced PLC stimulation by glutamate in predepolarized cells but not in control cells, suggesting that ryanodine receptors could play a role in the potentiation of the mGluR‐mediated activation of PLC by Ca2+ release in predepolarized cells.
Sympathectomy improves the ear's resistance to acoustic trauma – could stress render the ear more sensitive?
Authors: Horner Kathleen C. , Giraudet Fabrice , Lucciano Michel , Cazals Yves 
Published: March 2003

AbstractEmotional stress is a phenomenon experienced by many people at some time in their lives. Some of its early manifestations, such as unbearable loudness of ambient sounds and sensations of dizziness, might be linked to inner ear dysfunction. Although the inner ear is supplied with a substantial sympathetic innervation, previous studies have failed to demonstrate any significant functional impact. We show here that in the awake guinea pig and following unilateral ablation of the superior cervical ganglion, the temporary threshold shift induced by a 1‐min exposure to 8 kHz pure tone at 96 dB sound pressure level was reduced by as much as 40 dB. Of interest, the protective effect was bilateral suggesting an intimate relationship between the sympathetic and the olivocochlear efferent systems. The data presented here provide new evidence for a key role for the sympathetic system in modulating temporary threshold shifts following exposure to moderate sound stimulation. This opens new perspectives for investigation of sympathetic control in noise‐induced permanent hearing losses.
The retinal projection to the pregeniculate nucleus in normal and destriate monkeys
Authors: Cowey Alan , Johnson Helen , Stoerig Petra 
Published: March 2003

AbstractTaking advantage of the segregation of different classes of ganglion cell fibres in the optic tract, we investigated the ganglion cell class that projects to the pregeniculate nucleus (PGN) in the normal macaque monkey (Macaca mulatta and Macaca fascicularis) and following long‐standing removal of striate cortex in one hemisphere. Confining small pellets of horseradish peroxidase and biocytin into ventral or dorsal parts of the tract unilaterally, or placing several pellets throughout the tract, we labelled the retina retrogradely and the PGN anterogradely. Classification of ganglion cells according to soma size and dendritic morphology showed that implants in the dorsal part of the tract labelled predominantly, and perhaps exclusively, Pβ cells, and produced dense anterograde label in the parvocellular lateral geniculate nucleus as well in the PGN. Labelling of the PGN was sparse or absent following implants into the ventral aspect of the tract, which labelled the magnocellular geniculate nucleus anterogradely and chiefly Pα and Pγ cells retrogradely. The finding of a projection to the PGN from Pβ cells has implications for the permanent selective sparing of a subpopulation of these cells after removal of striate cortex and their contribution to wavelength processing in blindsight.
The occ1 gene is preferentially expressed in the primary visual cortex in an activity‐dependent manner: a pattern of gene expression related to the cytoarchitectonic area in adult macaque neocortex
Authors: Tochitani Shiro , Liang Fengyi , Watakabe Akiya , Hashikawa Tsutomu , Yamamori Tetsuo 
Published: March 2003

AbstractMarker molecules to visualize specific subsets of neurons are useful for studying the functional organization of the neocortex. One approach to identify such molecular markers is to examine the differences in molecular properties among morphologically and physiologically distinct neuronal cell types. We used differential display to compare mRNA expression in the anatomically and functionally distinct areas of the adult macaque neocortex. We found that a gene, designated occ1, was preferentially transcribed in the posterior region of the neocortex, especially in area 17. Complete sequence analysis revealed that occ1 encodes a macaque homolog of a secretable protein, TSC‐36/follistatin‐related protein (FRP). In situ hybridization histochemistry confirmed the characteristic neocortical expression pattern of occ1 and showed that occ1 transcription is high in layers II, III, IVA and IVC of area 17. In addition, occ1 transcription was observed selectively in cells of the magnocellular layers in the lateral geniculate nucleus (LGN). Dual labeling immunohistochemistry showed that the occ1‐positive neurons in area 17 include both γ‐aminobutyric acid (GABA)‐positive aspiny inhibitory cells and the α‐subunit of type II calcium/calmodulin‐dependent protein kinase (CaMKII α)‐positive spiny excitatory cells. With brief periods of monocular deprivation, the occ1 mRNA level decreased markedly in deprived ocular dominance columns of area 17. From this we conclude that the expression of occ1 mRNA is present in a subset of neurons that are preferentially localized in particular laminae of area 17 and consist of various morphological and physiological neuronal types, and, furthermore, occ1 transcription is subject to visually driven activity‐dependent regulation.
Stereotactic recordings of median nerve somatosensory‐evoked potentials in the human pre‐supplementary motor area
Authors: Barba Carmen , Frot Maud , Guénot Marc , Mauguière François 
Published: March 2003

AbstractMedian nerve somatosensory‐evoked potentials (SEPs) have been recorded using intracortical electrodes stereotactically implanted in the frontal lobe of eight epileptic patients in order to assess the waveforms, latencies and surface‐to‐depth distributions of somatosensory responses generated in the anterior subdivision of supplementary motor areas (SMAs), the so‐called pre‐SMA. Intracortical responses were analysed in two latency ranges: 0–50 ms and 50–150 ms after stimulus. In all patients, we recorded in the first 50 ms after stimulus two positive P14 and P20 potentials followed by a N30 negativity. In the hemisphere contralateral to stimulation, the P20–N30 potentials showed a clear amplitude decrease from the outer to the inner aspect of the frontal lobe with minimal amplitudes in the pre‐SMA. In the hemisphere ipsilateral to stimulus, P20 and N30 amplitudes were decreasing from mesial to lateral frontal cortex. In the 50–150 ms latency range, contacts implanted in the pre‐SMA recorded a negative potential in the 60–70 ms latency range which, in five patients, was followed by a positive response peaking 80–110 ms after stimulus. These potentials were not picked up by more superficial contacts. We conclude that no early SEP is generated in pre‐SMA in the first 50 ms after stimulation, while some potentials peaking in the 60–100 ms after stimulus are likely to originate from this cortical area. The latency of the pre‐SMA responses recorded in our patients supports the hypothesis that the pre‐SMA does not receive short‐latency somatosensory inputs via direct thalamocortical projections. More probably the pre‐SMA receives somatosensory inputs mediated by a polysynaptic transcortical transmission through functionally secondary motor and somatosensory areas.
The isochronic band hypothesis and climbing fibre regulation of motricity: an experimental study
Authors: Fukuda Masaji , Yamamoto Tomoya , Llinás Rodolfo 
Published: March 2003

AbstractThe dynamic organization of the olivocerebellar afferent input to Purkinje cells was examined in rat cerebellar cortex. The distribution of synchronous Purkinje cell complex spike activity was characterized, bilaterally, utilizing multiple electrode recordings in crus IIa folium under ketamine anaesthesia. The results confirmed the existence of rostrocaudal complex spike isochronicity bands with a mediolateral width of 500 µm. For a given band, no finer spatial submicrostructures could be discerned at a first‐order approximation (two‐dimensional projection). Closer analysis determined that isochronicity between bands is not continuous in space but demonstrates discrete discontinuities at the mediolateral boundaries. Principal component multivariate analysis revealed that the first principal component of the spatio‐temporal variance is synchronicity along the rostrocaudal band with a decreased level of coupling in the mediolateral direction at the band boundary. Furthermore, this discrete banding isochronicity is organized by the distribution of feedback inhibition from the cerebellar nuclei on to the inferior olive nucleus. The usual multiple band structure can be dynamically altered to a single wide‐band dynamic architecture, or to other patterns of activity, as may be required by movement coordination.
Bilaterally synchronous complex spike Purkinje cell activity in the mammalian cerebellum
Authors: Yamamoto Tomoya , Fukuda Masaji , Llinás Rodolfo 
Published: March 2003

AbstractComplex spike activity was simultaneously recorded from 96 Purkinje cells in the rat cerebellar cortex. Rostrocaudal complex spike synchronicity bands were studied in crus I, IIa and IIb and in vermal lobule 6c. Detailed analysis in crus IIa revealed that complex spike activity was staggered sequentially with a 20–50 cm/sec ‘propagation velocity’ in the mediolateral direction, and that such activity was bilaterally synchronous. The ‘propagation’ of complex spike activity was symmetrical between right and left crus IIa. Temporally, the neurons that aligned in the rostrocaudal direction typically generated complex spikes close to simultaneously. The correlation of complex spike firing was high between crus IIa and crus IIb, moderate between crus IIa and vermis 6c, and relatively low between Purkinje cells in crus I and crus IIa. These results indicate that, whilst discrete boarders exist between different isochronicity bands, these bands do communicate with each other in the mediolateral direction via slow ‘propagation waves’ that loosely bind their activity. The results indicate that the olivocerebellar system is organized, bilaterally, to take advantage of the timing signals generated at the inferior olive nucleus.
Peripheral nerve injury fails to induce growth of lesioned ascending dorsal column axons into spinal cord scar tissue expressing the axon repellent Semaphorin3A
Authors: Pasterkamp R. Jeroen , Anderson Patrick N. , Verhaagen Joost 
Published: March 2003

AbstractWe have investigated the hypothesis that the chemorepellent Semaphorin3A may be involved in the failure of axonal regeneration after injury to the ascending dorsal columns of adult rats. Following transection of the thoracic dorsal columns, fibroblasts in the dorsolateral parts of the lesion site showed robust expression of Semaphorin3A mRNA. In addition, dorsal root ganglion (DRG) neurons with projections through the dorsal columns to the injury site persistently expressed both Semaphorin3A receptor components, neuropilin‐1 and plexin‐A1. These ascending DRG collaterals failed to invade scar regions occupied by Semaphorin3A‐positive fibroblasts, even in animals which had received conditioning lesions of the sciatic nerve to enhance regeneration. Other axon populations in the dorsal spinal cord were similarly unable to penetrate Semaphorin3A‐positive scar tissue. These data suggest that Semaphorin3A may create an exclusion zone for regenerating dorsal column fibres and that enhancing the intrinsic regenerative response of DRG neurons has only limited effects on axonal regrowth. Tenascin‐C and chondroitin sulphate proteoglycans were also detected at the injury site, which was largely devoid of central nervous system (CNS) myelin, showing that several classes of inhibitory factors, including semaphorins, with only partially overlapping spatial and temporal patterns of expression are in a position to participate in preventing regenerative axonal growth in the injured dorsal columns. Interestingly, conditioning nerve injuries enabled numerous ascending DRG axons to regrow across areas of strong tenascin‐C and chondroitin sulphate proteoglycan expression, while areas containing Semaphorin3A and CNS myelin were selectively avoided by (pre)primed axonal sprouts.
The synthetic cannabinoid WIN55212‐2 decreases the intraocular pressure in human glaucoma resistant to conventional therapies
Authors: Porcella Anna , Maxia Chiara , Gessa Gian Luigi , Pani Luca 
Published: March 2003

AbstractThe search for new ocular hypotensive agents represents a frontier of current eye research because blindness due to optic neuropathy occurs insidiously in 10% of all patients affected by glaucoma. Cannabinoids have been proposed to lower intraocular pressure by either central or peripheral effects but a specific mechanism for this action has never been elucidated. We recently demonstrated the presence of the central cannabinoid receptor (CB1) mRNA and protein in the human ciliary body. In the present study we show that the synthetic CB1 receptor agonist, WIN 55212–2, applied topically at doses of 25 or 50 µg (n = 8), decreases the intraocular pressure of human glaucoma resistant to conventional therapies within the first 30 min (15 ± 0.5% and 23 ± 0.9%, respectively). A maximal reduction of 20 ± 0.7% and 31 ± 0.6%, respectively, is reached in the first 60 min. These data confirm that CB1 receptors have direct involvement in the regulation of human intraocular pressure, and suggest that, among various classes of promising antiglaucoma agents, synthetic CB1 receptor agonists should deserve further research and clinical development.
The anabolic‐androgenic steroid nandrolone decanoate affects the density of dopamine receptors in the male rat brain
Authors: Kindlundh Anna M. S. , Lindblom Jonas , Bergström Lena , Wikberg Jarl E. S. , Nyberg Fred 
Published: March 2003

AbstractIn recent years a male group of anabolic‐androgenic steroid misusers has been identified to share socio‐demographic and personality related background factors with misusers of psychotropic substances, as well as being involved in habits of multiple drug use. The present study aimed to assess whether anabolic‐androgenic steroids (AAS) would affect the density of the dopamine receptors in areas implicated in reward and behaviour in the male rat brain. The effects of 2 weeks of treatment with i.m. injections of nandrolone decanoate (15 mg/kg/day) on the expression of the D1‐like and D2‐like receptors were evaluated by autoradiography. Specific binding of D1‐like receptors was significantly down regulated in the caudate putamen, the nucleus accumbens core and shell. D2‐like receptor densities were down regulated in the nucleus accumbens shell, but up regulated in the caudate putamen, the nucleus accumbens core and the ventral tegmental area. These results are compatible with nandrolone induced neuroadaptive alterations in dopamine circuits associated with motor functions and behavioural paradigms known to be affected following AAS misuse.
Properties of entorhinal cortex deep layer neurons projecting to the rat dentate gyrus
Authors: Gloveli Tengis , Dugladze Tamar , Schmitz Dietmar , Heinemann Uwe 
Published: March 2003

AbstractMedial entorhinal cortex (EC) deep layer neurons projecting to the dentate gyrus (DG) were studied. Neurons, retrogradely‐labelled with rhodamine‐dextran‐amine were characterized electrophysiologically with the patch clamp technique and finally labelled with biocytin. Pyramidal and nonpyramidal neurons form projections from the deep layers of the EC to the molecular layer of the DG. In addition, both classes of projection neurons send ascending axon collaterals to the superficial layers of the EC. Both classes of neurons were characterized physiologically by regular action potential firing upon depolarizing current injection. While a substantial number of pyramidal projection cells showed intrinsic membrane potential oscillations, none of the studied nonpyramidal cells exhibited oscillations. Despite the morphological similarity of bipolar and multipolar cells to those of GABAergic interneurons in the EC, their electrophysiological characteristics were similar to those of principal neurons and immunocytochemistry for GABA was negative. We conclude, that neurons of the deep layers of the medial EC projecting to the DG may function as both local circuit and projecting neurons thereby contributing to synchronization between deep layers of the EC, superficial layers of the EC and the DG.
Corticosterone differentially modulates expression of corticotropin releasing factor and arginine vasopressin mRNA in the hypothalamic paraventricular nucleus following either acute or repeated restraint stress
Authors: Pinnock S. B. , Herbert J. 
Published: March 2003

AbstractExposing rats to repeated restraint stress induces well‐characterized adaptations in the expression of either corticotropin‐releasing factor (CRF) or arginine‐vasopressin (AVP) mRNA in the parvocellular neurons of the hypothalamic paraventricular nucleus (PVN). The effects of regulating corticosterone levels on this adaptation was studied in male rats. In intact rats, acute restraint stress increased the expression of CRF mRNA whilst AVP mRNA expression was no different to control. Repeated exposure resulted in habituation of CRF expression, whereas AVP mRNA increased above that seen in either non stressed or acutely stressed animals. In adrenalectomised rats with replacement pellets of corticosterone that replicated blood levels approximating to the daily trough (mean levels 37–65 ng/mL), basal CRF expression levels were raised, but the response to acute stress was still observed. However, the habituation seen in normal animals that had been repeatedly stressed was prevented, so that CRF mRNA levels continued to be raised after repeated stress. By contrast, the AVP response to both acute and repeated stress was unaltered in these low‐dose corticosterone‐treated rats compared with controls. Higher dose pellets, which resulted in blood levels around those of the daily maximum (mean 118–141 ng/mL) had the opposite effects. There was no change compared to intact rats in the expression of CRF mRNA following either acute or repeated stress, but the expected increase in AVP following repeated restraint was prevented. These experiments show that corticosterone has important modulating effects on the adaptive pattern of both CRF and AVP mRNA expression in the parvocellular PVN. The ‘set‐point’ of corticosterone differs; for CRF, experiencing higher levels is necessary for subsequent adaptation to repeated restraint to occur, whereas for AVP a return to lower levels is necessary to allow this peptide to respond to repeated stress.
Neuroprotection by estrogen via extracellular signal‐regulated kinase against quinolinic acid‐induced cell death in the rat hippocampus
Authors: Kuroki Yasutomi , Fukushima Kouji , Kanda Yasunari , Mizuno Katsushige , Watanabe Yasuhiro 
Published: March 2003

AbstractExtracellular signal‐regulated kinase (ERK) belongs to the family of mitogen‐activated protein kinases (MAPKs), which are serine‐threonine kinases activated by phosphorylation in response to a variety of mitogenic signals. We previously reported that 17β‐estradiol rapidly activates ERK in the rat hippocampus. However, the physiological role of this rapid activation of ERK by estrogen in vivo has not yet been elucidated. This study investigated whether ERK may participate in mediating the neuroprotective effects of estrogen against quinolinic acid (QA) toxicity in the rat hippocampus in vivo. Injection of QA into the hippocampi of male rats produced a loss of Nissl‐stained neurons in the CA1 after 24 h. Prior administration of 17β‐estradiol (50 pmol/animal) to the ventricles prevented the QA‐induced decrease in Nissl‐stained neurons. Pretreatment with U0126, an inhibitor of MAPK/ERK kinase, inhibited the rapid activation of ERK by 17β‐estradiol in the rat hippocampus. Moreover, the neuroprotective effects of 17β‐estradiol against QA toxicity were blocked by the pretreatment with U0126. U0126 alone did not produce a loss of neurons. These results indicate that ERK mediates estrogen neuroprotection after QA toxicity in the rat hippocampus.
Distribution of transcripts for the brain‐specific GDP/GTP exchange factor collybistin in the developing mouse brain
Authors: Kneussel M. , Engelkamp D. , Betz H. 
Published: March 2003

AbstractThe dbl‐like GDP/GTP exchange factor, collybistin, binds to the receptor anchoring protein gephyrin and activates the Rho‐like GTPase Cdc42. Collybistin was found in two splice variants I and II, both of which share a tandem Dbl homology/pleckstrin homology (DH/PH) domain. In heterologous expression systems, collybistin II induces the formation of submembraneous gephyrin aggregates and therefore has been implicated in inhibitory synapse formation. Expression of collybistin is restricted to neuronal tissues and is predominantly found in brain. Here, we investigated the spatio‐temporal distribution of collybistin transcripts in the embryonic mouse brain and compared it to gephyrin and glycine receptor mRNA patterns. Our data show that collybistin expression is upregulated when neurons become postmitotic and start to differentiate.