bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential patterns of semaphorin expression in the developing rat brain
Authors: Skaliora Irini , Singer Wolf , Betz Heinrich , Püschel Andreas W. 
Published: March 2003

AbstractSemaphorins are a large family of cell‐surface and secreted proteins that have been shown to function as chemorepellents or inhibitors of growth cones of peripheral neurons, yet little is known about their role in patterning central pathways. In order to examine whether semaphorins may be involved in guiding the formation of the reciprocal thalamocortical connections in the rat, we have analysed the spatial and temporal expression of five recently identified rodent semaphorins (semB, C, D, F and G) using in situ hybridization. Transcripts of all five genes were present throughout the period examined (E15–P7) and displayed highly specific spatiotemporal distributions. We have based our discussion of putative semaphorin effects on their known functions as chemorepellents and found their spatiotemporal expression patterns compatible with such a role in several developmental events. Specifically, semaphorins are in the position to: (i) prevent neurite extension into the ventricular neuroepithelium throughout the brain; (ii) confer non‐permissive properties to the embryonic cortical plate, hence regulating the radial invasion of corticopetal afferents; (iii) confine axonal extension to the intermediate zone and subplate; (iv) maintain the fasciculated state of thalamocortical and corticothalamic axons, and prevent them from branching while they grow through the striatum; and (v) restrict the terminal arborizations of thalamic afferents to layer IV. The evidence that different semaphorin genes are often co‐expressed further suggests that the various molecules might interact in synergistic ways. Taken together, our results support the hypothesis that semaphorins could act as guidance signals in the development of the thalamocortical projections and suggest that innervation specificity is achieved through the combined action of multiple guidance cues. Furthermore, these data provide a basis for the design of functional assays and the study of mice carrying knockouts in specific semaphorin genes.
Immortalized gonadotropin‐releasing hormone neurons secrete γ‐aminobutyric acid – evidence for an autocrine regulation
Authors: Ahnert‐Hilger G. , John M. , Kistner U. , Wiedenmann B. , Jarry H. 
Published: March 2003

AbstractThe immortalized hypothalamic neuronal cell lines GT1‐1 and GT1‐7 represent unique model systems to investigate the physiological control of gonadotropin‐releasing hormone (GnRH) secretion.Using immunofluorescence microscopy, key proteins of regulated exocytosis, e.g. synaptotagmin, synaptobrevin and SNAP‐25 (synaptosomal associated protein of 25 kDa) were found in GT1 neurons. In addition, GT1 neurons contained synaptophysin, a marker protein for small synaptic vesicles (SSVs) which are responsible for the storage of neurotransmitters such as γ‐aminobutyric acid (GABA). Upon subcellular fractionation, a lighter vesicle population characterized by synaptophysin separated from a denser vesicle population containing GnRH. Both vesicle populations contained synaptobrevin and synaptotagmin. Besides GnRH, GT1 neurons expressed glutamic acid decarboxylase at the mRNA‐level and synthesized GABA. More importantly, GT1 neurons took up and stored 3H‐GABA. The stored GABA was released after stimulation with increasing K+ concentrations and by α‐latrotoxin. Reducing the extracellular Ca2+‐concentration abolished stimulated secretion, indicating that GABA was released by regulated exocytosis. Hormone secretion from GT1 neurons is controlled by GABA via GABAA and GABAB receptors reflecting the situation in vivo.Our data provide the first evidence that GT1 neurons possess a second regulated secretory pathway sustained by SSVs storing and releasing GABA. The released GABA influences GnRH secretion by an auto‐ or paracrine loop.
Brain Ac39/physophilin: cloning, coexpression and colocalization with synaptophysin
Authors: Carrión‐Vázquez Mariano , Fernández Ana María , Chowen Julie , Nieto‐Sampedro Manuel 
Published: March 2003

AbstractPhysophilin is an oligomeric protein that binds the synaptic vesicle protein synaptophysin constituting a complex that has been hypothesized to form the exocytotic fusion pore. Microsequencing of several physophilin peptides putatively identified this protein as the Ac39 subunit of the V‐ATPase. Ac39 has recently been shown to be present in a synaptosomal complex which, in addition to synaptophysin, includes the bulk of synaptobrevin II, and subunits c and Ac115 of the V0 sector of the V‐ATPase. We have cloned physophilin from mouse brain and found a differential region of 12 amino acids when compared with the previously reported sequence of Ac39 from bovine adrenal medulla. RT‐PCR cloning from the bovine adrenal medulla demonstrates that sequencing errors occurred in the previous cloning study, and shows that the amino acid sequences of physophilin and Ac39 are completely identical. In situ hybridization in rat brain reveals a largely neuronal distribution of Ac39/physophilin mRNA which spatio‐temporally correlates with those of subunit c and synaptophysin. Immunohistochemical analysis shows that Ac39/physophilin is mostly concentrated in the neuropil with a pattern identical to subunit A and very similar to synaptophysin. Double‐labelling immunofluorescence shows a complete colocalization of Ac39/physophilin with subunit A and a partial colocalization with synaptophysin in the neuropil. Our findings bring anatomical support for the in vivo occurrence of the synaptophysin‐Ac39/physophilin interaction and further suggest a coordinated transcription of V‐ATPase and synaptophysin genes. A putative role of Ac39/physophilin in the inactivation of the V‐ATPase by disassembly of its V1 sector is also discussed.
Scalp recorded direct current brain potentials during human sleep
Authors: Marshall Lisa , Mölle Matthias , Fehm Horst L. , Born Jan 
Published: March 2003

AbstractThe direct current (DC) potential recorded from the scalp of awake humans has been considered a reflection of general changes in cortical excitability. This study examined DC potential shifts in humans during a night of continuous sleep. Standard polysomnographic recordings and skin temperature were measured simultaneously. Contrary to expectations, average DC potential level indicated higher negativity during nonrapid eye movement (NREM) sleep than REM sleep and wakefulness. Moreover, a dynamic regulation of the DC potential level was revealed in association with the NREM–REM sleep cycle comprising four successive phases: (i) a steep ‘NREM‐transition‐negative shift’ during the initial 10–15 min of the NREM sleep period; (ii) a more subtle ‘NREM‐positive slope’ during the subsequent NREM sleep period; (iii) a steep ‘REM‐transition‐positive shift’ starting shortly prior to the REM sleep period, and (iv) a ‘REM‐negative slope’, characterizing the remaining greater part of the REM sleep period. DC potential changes were only weakly related to changes in slow‐wave activity (r2 < 0.18). The NREM‐negative slope and REM‐positive slope could reflect, respectively, gradually increasing and decreasing cortical excitability resulting from widespread changes in the depolarization of apical dendrites. In contrast, the NREM‐transition‐negative shift and the REM‐transition‐positive shift may reflect the progression and retrogression, respectively, of a long‐lasting hyperpolarization in deeply lying neurons.
Intraventricular galanin modulates a 5‐HT1A receptor‐mediated behavioural response in the rat
Authors: Misane Ilga , Razani Haleh , Jansson Fu‐Hua Wang anders , Fuxe Kjell , Ögren Sven Ove 
Published: March 2003

AbstractThe present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5‐HT) neurotransmission in vivo and, particularly, 5‐HT1A receptor‐mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5‐HT1A agonist 8‐hydroxy‐2‐(di‐n‐propyloamino)tetralin (8‐OH‐DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5‐HT1A receptors in the CNS. Galanin dose‐dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8‐OH‐DPAT. This 8‐OH‐DPAT dose produced signs of the 5‐HT syndrome indicating a postsynaptic 5‐HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5‐HT syndrome were completely blocked by the 5‐HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8‐OH‐DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5‐HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5‐HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8‐OH‐DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100–200 μm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin‐immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin‐immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5‐HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.
Association Basolateral amygdala stimulation evokes glutamate receptor‐dependent dopamine efflux in the nucleus accumbens of the anaesthetized rat
Authors: Floresco Stan B. , Yang Charles R. , Phillips Anthony G. , Blaha Charles D. 
Published: March 2003

AbstractAfferents from the basolateral amygdala and dopamine projections from the ventral tegmental area to the nucleus accumbens have both been implicated in reward‐related processes. The present study used in vivo chronoamperometry with stearate‐graphite paste electrodes in urethane‐anaesthetized rats to determine how basolateral amygdala efferents to the nucleus accumbens synaptically regulate dopamine efflux. Repetitive‐pulse (20 Hz for 10 s) electrical stimulation of the basolateral amygdala evoked a complex pattern of changes in monitored dopamine oxidation currents in the nucleus accumbens related to dopamine efflux. These changes were characterized by an initial increase that was time‐locked to stimulation, a secondary decrease below baseline, followed by a prolonged increase in the dopamine signal above baseline. The effects of burst‐patterned stimulation (100 Hz, 5 pulses/burst, 1‐s interburst interval, 40 s) of the basolateral amygdala on the basal accumbens dopamine signal were similar to those evoked by 20 Hz stimulation, with the lack of a secondary suppressive component. Infusions of the ionotropic glutamate receptor antagonists (±)‐2‐amino‐5‐phosphonopentanoic acid (APV) or 6,7‐dinitroquinoxaline‐2,3‐dione (DNQX) into the nucleus accumbens dose‐dependently blocked or attenuated the initial and prolonged increases in the dopamine signal following 20 Hz or burst‐patterned basolateral amygdala stimulation. Infusions of the metabotropic glutamate receptor antagonist (+)‐α‐methyl‐4‐carboxyphenylglycine selectively blocked the intermediate suppressive effect of 20 Hz basolateral amygdala stimulation on dopamine oxidation currents. Blockade of glutamate receptors or inhibition of dopamine neuronal activity via infusions of either APV + DNQX, lidocaine or γ‐hydroxybutyric acid, respectively, into the ventral tegmental area did not effect the pattern of changes in the accumbens dopamine signal evoked by basolateral amygdala stimulation. These data suggest that the glutamatergic basolateral amygdala inputs to nucleus accumbens dopamine terminals synaptically facilitate or depress dopamine efflux, and these effects are independent of dopamine neuronal firing activity. Moreover, these results imply that changes in nucleus accumbens dopamine levels following presentation of reward‐related stimuli may be mediated, in part, by the basolateral amygdala.
Potentiation of murine astrocyte antioxidant defence by bcl‐2: protection in part reflects elevated glutathione levels
Authors: Papadopoulos Marios C. , Koumenis Iphigenia L. , Xu Lijun , Giffard Rona G. 
Published: March 2003

AbstractOverexpression of the proto‐oncogene bcl‐2 has been shown to protect a variety of cell types from oxidative and non‐oxidative injury, blocking apoptotic and necrotic types of cell death. Retroviral vectors were used to stably overexpress bcl‐2 in primary murine astrocyte cultures with more than 95% efficiency. Compared to β‐galactosidase‐expressing and uninfected control cells, bcl‐2 overexpressing astrocytes suffered < 40% injury after 24 h glucose deprivation, while controls were essentially completely injured. After exposure to 0.2 mm hydrogen peroxide, the bcl‐2 overexpressing astrocytes suffered < 40% the injury seen in controls. In contrast, when the cultures were injured by combined oxygen–glucose deprivation, no difference in the extent or time course of injury was found between cells overexpressing bcl‐2 and those expressing β‐galactosidase. To investigate one possible mechanism of bcl‐2 protection, we measured the levels of glutathione and three antioxidant enzymes. Astrocytes overexpressing bcl‐2 had elevated glutathione levels (130–200%), increased superoxide dismutase (170%) and glutathione peroxidase (140%) activities compared with β‐galactosidase‐expressing controls. Bcl‐2 overexpressing astrocytes suffered less lipid peroxidation after glucose deprivation, as assessed by cis‐parinaric acid fluorescence, and demonstrated more rapid removal of hydrogen peroxide from the medium. When glutathione levels were decreased 80% by pretreatment with buthionine sulfoximine, the extent of protection from glucose deprivation of bcl‐2 overexpressing cells was decreased by about half. Increased antioxidant defence contributes to protection from glucose deprivation in bcl‐2 overexpressing astrocytes.
A dopamine‐μ1 opioid link in the rat ventral tegmentum shared by palatable food (Fonzies) and non‐psychostimulant drugs of abuse
Authors: Tanda Gianluigi , Di Chiara Gaetano 
Published: March 2003

AbstractThe role of μ1 opioid receptors in the stimulation of dopamine transmission in the rat nucleus accumbens by an unusual palatable food (Fonzies) and non‐psychostimulant drugs of abuse was investigated by the use of naloxonazine, a pseudo‐irreversible antagonist of μ1 opioid receptors. Feeding of Fonzies stimulated dopamine release in the medial prefrontal cortex and in the shell, but not in the core of the nucleus accumbens. Pretreatment with naloxonazine given systemically (15 mg/kg i.p. 20 h before) completely prevented the stimulation of dopamine release in the shell of the nucleus accumbens by Fonzies without affecting that in the prefrontal cortex. Systemic pretreatment with naloxonazine reduced or, depending on the dose, abolished, the stimulation of dopamine release in the nucleus accumbens shell by morphine, nicotine and ethanol, but did not affect that by haloperidol. Naloxonazine also prevented the stimulatory effects of Fonzies, nicotine and morphine on nucleus accumbens dopamine transmission when infused bilaterally in the ventral tegmental area. The results indicate that μ1 opioid receptors in the ventral tegmentum play a major role in the stimulant effects of food and drugs of abuse on mesolimbic dopamine transmission.
Interleukin‐1β and the interleukin‐1 receptor antagonist act in the striatum to modify excitotoxic brain damage in the rat
Authors: Lawrence Catherine B. , Allan Stuart M. , Rothwell Nancy J. 
Published: March 2003

AbstractThe cytokine interleukin‐1 (IL‐1) has been implicated in ischaemic, traumatic and excitotoxic brain damage. The results presented here reveal novel actions of IL‐1 in the striatum which markedly exacerbate cortical neuronal damage elicited by local excitotoxins in the striatum or cortex.Intrastriatal infusion of IL‐1 receptor antagonist, IL‐1ra, markedly inhibited striatal neuronal damage caused by N‐methyl‐d‐aspartate (NMDA) or α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor activation in the rat. In contrast, intracortical infusion of IL‐1ra failed to inhibit NMDA or AMPA receptor‐induced damage in the cortex.Intrastriatal co‐infusion of IL‐1β with the NMDA or AMPA receptor agonist did not affect local striatal damage induced by activation of either glutamate receptor subtype, but caused extensive cortical damage when administered into the striatum with AMPA. This secondary damage was significantly reduced by pretreatment with the NMDA receptor antagonist (MK‐801), which did not affect local (striatal) damage caused by AMPA. Infusion of IL‐1β into the striatum (but not the cortex) markedly enhanced cortical damage caused by infusion of an NMDA or AMPA receptor agonist into the cortex.These data reveal selective actions of IL‐1 and IL‐1ra in the striatum, which influence cortical neuronal loss and suggest that IL‐1 selectively enhances damage caused by AMPA receptor activation.
Layer‐specific dendritic regression of pyramidal cells with ageing in the human prefrontal cortex
Authors: de Brabander  , Kramers  , Uylings  
Published: March 2003

AbstractThe dendritic field of pyramidal neurons in cortical layers IIIc and V of the prefrontal cortex in ageing humans was studied. The three‐dimensional branching pattern of the basilar dendrites of Golgi–Cox impregnated neurons was analysed in the middle frontal gyrus (areas 9 and 46) in eight subjects between the ages of 49 and 90 years, all without a neurological or psychiatric disorder.The results revealed a significant regression of the layer V dendritic pattern with increasing age, but the layer IIIc neurons did not show any age‐related changes. Together with our earlier data on the postnatal development of the same cell types in the prefrontal cortex, we hypothesize that the layer V neurons in the prefrontal cortex start to regress from the fifth decade onwards, in contrast to the layer IIIc neurons which remain stable from puberty on.We conclude that pyramidal cells in layer IIIc and V in a similar cortical region undergo a differential ageing effect.
Differentiation of rat hypothalamic dopaminergic neurons is stimulated in vitro by target cells: the melanotrophs
Authors: Egles  , René  , Varon  , Louis  , Félix  , Schimchowitsch  
Published: March 2003

AbstractWe have investigated in vitro the influence of pituitary intermediate lobe melanotrophs on the differentiation of their afferent hypothalamic dopaminergic neurons. The presence of melanotrophs in primary cultures of foetal hypothalamic neurons induces an increase of the number of dopaminergic neurons (while the total neuronal population remains unchanged) and induces a stimulation of their neuritic outgrowth. These effects are mediated by diffusible factors since they are reproduced by application of conditioned medium issued from co‐cultures with intermediate lobe cells from newborn rats. Moreover, by immunoneutralization of α‐melanocyte‐stimulating hormone (αMSH) in the co‐culture or conditioned medium, or by application of the peptide itself, we demonstrate that the neuritotrophic effect on dopaminergic neurons is mediated by αMSH, the main secretory product of melanotrophs, whereas the inductive effect on the number of dopaminergic neurons is attributable to another diffusible neurotrophic factor(s) present in foetal, but not adult, adenohypophysis. Similar effects are observed on cultures of newborn hypothalamic neurons. However, at this stage of neuronal development, αMSH also increases the number of dopaminergic neurons, which could be due to a change of neuronal receptivity. We show that the neuritotrophic influence of αMSH is restricted to the dopaminergic neurons connected to the melanotrophs, and that in addition, these neurons systematically co‐express the tyrosine hydroxylase and glutamate decarboxylase as the neurons innervating the melanotrophs in situ. These findings indicate that the differentiation of dopaminergic hypothalamic neurons is influenced by the target cells, melanotrophs, and that this trophic influence implicates αMSH.
Endogenous nerve growth factor regulates the sensitivity of nociceptors in the adult rat
Authors: Bennett David L. H. , Koltzenburg Martin , Priestley John V. , Shelton David L. , McMahon Stephen B. 
Published: March 2003

AbstractNerve growth factor (NGF) has a well characterized role in the development of the nervous system and there is evidence that it interacts with nociceptive primary afferent fibres. Here we applied a synthetic tyrosine kinase A IgG (trkA‐IgG) fusion molecule for 10–12 days to the innervation territory of the purely cutaneous saphenous nerve in order to bind, and thereby neutralize endogenous NGF in adult rats. Using neurophysiological analysis of 152 nociceptors we now show that sequestration of NGF results in specific changes of their receptive field properties. The percentage of nociceptors responding to heat dropped significantly from a normal 57% to 32%. This was accompanied by a rightward shift and a reduced slope of the stimulus response function relating the intracutaneous temperature to the neural response. The number of nociceptors responding to application of bradykinin was also significantly reduced from a normal of 28% to 8%. In contrast, the threshold for mechanical stimuli and the response to suprathreshold stimuli remained unaltered, as did the percentage of nociceptors responding to noxious cold. The reduced sensitivity of primary afferent nociceptors was accompanied by a reduction in the innervation density of the epidermis by 44% as assessed with quantitative immunocytochemical analysis of the panaxonal marker PGP 9.5. This demonstrates that endogenous NGF in the adult specifically modulates the terminal arborization of unmyelinated fibres and the sensitivity of primary afferent nociceptors to thermal and chemical stimuli in vivo.