bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopamine control of striatal gene expression during development: relevance to knockout mice for the dopamine transporter
Authors: Fauchey Valérie , Jaber Mohamed , Bloch Bertrand , Le Moine Catherine 
Published: March 2003

AbstractThe aim of this study was to determine at which developmental stage and how dopamine regulates the expression of striatal dopamine receptor and neuropeptide mRNAs. For this, we studied the expression of these mRNAs, in relation to dopamine innervation, in normal mice from gestational day 13 (G13) to adult. Particularly, we investigated the adaptive changes in the expression of these markers in mice lacking the dopamine transporter during development. We detected tyrosine hydroxylase, by immunohistochemistry, in the ventral mesencephalon and the striatal anlage in both genotypes at G13, whereas the dopamine transporter appeared in the striatum of normal mice at G14. By in situ hybridization, we detected striatal dopamine D1, D2, D3 receptor, and substance P mRNAs at G13, preproenkephalin A mRNA at G14 and dynorphin mRNA at G17 in normal mice. Although the time of initial detection and the distribution were not affected in mutant mice, quantitative changes were observed. Indeed, D1 and D2 receptor as well as preproenkephalin A mRNA levels were decreased from G14 on, and dynorphin mRNA level was increased from G17 on. In contrast, substance P mRNA level was unaffected. Our data demonstrate that the influence of dopamine on striatal neurons occurs early during the development of the mesostriatal system as quantitative changes appeared in mutant mice as soon as G14. These findings bring new insights to the critical influence of dopamine on the expression of striatal dopamine receptor and neuropeptide mRNAs during development, and suggest that mesostriatal dopamine transmission functions from G14 on.
Impaired cholinergic function in cell lines derived from the cerebral cortex of normal and trisomy 16 mice
Authors: Allen David D. , Martín José , Arriagada Christian , Cárdenas Ana María , Rapoport Stanley I. , Caviedes Raúl , Caviedes Pablo 
Published: March 2003

AbstractMurine trisomy 16 is an animal model of human Down's syndrome. We have successfully established permanently growing cell lines from the cerebral cortex of normal and trisomy 16 foetal mice using an original procedure. These lines, named CNh (derived from a normal animal) and CTb (derived from a trisomic foetus), express neuronal markers. Considering that Down's syndrome exhibits cholinergic deficits, we examined cholinergic function in these lines, using incorporation of [3H]‐choline and fractional release studies. After 1, 3 and 5 min of [3H]‐choline incubation, CTb cell uptake was lower by ∼ 50% compared to controls. Hemicholinium‐3 significantly reduced the incorporation of [3H]‐choline in both CNh and CTb cells at high concentration (10 μm), suggesting high‐affinity choline transport. However, CTb cells exhibited greater sensitivity to the blocker. For fractional release experiments, the cells were stimulated by K+ depolarization, glutamate or nicotine. When depolarized, CTb cells showed a 68% reduction in fractional release of [3H]‐acetylcholine compared to CNh cell line, and a 45% reduction when stimulated by nicotine. Interestingly, glutamate induced similar levels of release in both cell types. The results indicate the existence of cholinergic dysfunction in CTb cells when compared to CNh, similar to that reported for primary cultures of trisomy 16 brain tissue (Fiedler et al. 1994, Brain Res., 658, 27–32). Thus, the CTb cell line may serve as a model for the study of Down's syndrome pathophysiology.
Pindolol excites dopaminergic and adrenergic neurons, and inhibits serotonergic neurons, by activation of 5‐HT1Areceptors
Authors: Lejeune F. , Millan M. J. 
Published: March 2003

AbstractPindolol accelerates the clinical actions of selective serotonin reuptake inhibitors (SSRIs) in man, and modulates extracellular levels of monoamines in corticolimbic structures in rats. Herein, we examined its influence upon electrical activity of serotonergic, dopaminergic and adrenergic perikarya in the dorsal raphe nucleus (DRN), ventral tegmental area (VTA) and locus coeruleus (LC) of anaesthetized rats. In analogy to the serotonin1A(5‐HT1A) agonist, 8‐OH‐DPAT (−100%), pindolol dose‐dependently (0.063– 1.0 mg/kg) decreased (−70%) the firing rate of serotonergic neurons. The inhibitory action of pindolol was abolished by the selective 5‐HT1Aantagonist, WAY‐100,635 (0.031 mg/kg). In contrast, 8‐OH‐DPAT (+26%) and pindolol (0.25–4.0 mg/kg, +60%) dose‐dependently increased the firing rate of dopaminergic cells. Of 57 neurons recorded (pindolol, 2.0 mg/kg), 36 (63%) were excited, 11 (19%) were unaffected and 10 (18%) were inhibited. This variable influence could be attributed to regularly firing neurons in the parabrachial subdivision, inasmuch as all neurons in the paranigral subnucleus were excited. The facilitation of firing by pindolol was accompanied by an increase in burst firing throughout the VTA. Both the increases in burst firing and in firing rate were reversed by WAY‐100,635 (0.031 mg/kg). Finally, the electrical activity of adrenergic neurons was dose‐dependently enhanced by 8‐OH‐DPAT and pindolol (+99% and +83%, respectively). WAY‐100,635 reversed this excitation and, itself, inhibited the activity of adrenergic neurons. In conclusion, via engagement of 5‐HT1Areceptors, pindolol inhibits serotonergic, and activates dopaminergic and adrenergic, neurons in anaesthetized rats. Such actions may contribute to its influence upon mood, both alone and in association with antidepressant agents.
Involvement of the human frontal eye field and multiple parietal areas in covert visual selection during conjunction search
Authors: Donner Tobias , Kettermann Andreas , Diesch Eugen , Ostendorf Florian , Villringer Arno , Brandt Stephan A. 
Published: March 2003

AbstractSearching for a target object in a cluttered visual scene requires active visual attention if the target differs from distractors not by elementary visual features but rather by a feature conjunction. We used functional magnetic resonance imaging (fMRI) in human subjects to investigate the functional neuroanatomy of attentional mechanisms employed during conjunction search. In the experimental condition, subjects searched for a target defined by a conjunction of colour and orientation. In the baseline condition, subjects searched for a uniquely coloured target, regardless of its orientation. Eye movement recordings outside the scanner verified subjects' ability to maintain fixation during search. Reaction times indicated that the experimental condition was attentionally more demanding than the baseline condition. Differential activations between conditions were therefore ascribed to top‐down modulation of neural activity. The frontal eye field, the ventral precentral sulcus and the following posterior parietal regions were consistently activated: (i) the postcentral sulcus; (ii) the posterior; and (iii) the anterior part of the intraparietal sulcus; and (iv) the junction of the intraparietal with the transverse occipital sulcus. Parietal regions were spatially distinct and displayed differential amplitudes of signal increase with a maximal amplitude in the posterior intraparietal sulcus. Less consistent activation was found in the lateral fusiform gyrus. These results suggest an involvement of the human frontal eye field in covert visual selection of potential targets during search. These results also provide evidence for a subdivision of posterior parietal cortex in multiple areas participating in covert visual selection, with a major contribution of the posterior intraparietal sulcus.
Glucocorticoid enhancement of memory consolidation in the rat is blocked by muscarinic receptor antagonism in the basolateral amygdala
Authors: Power Ann E. , Roozendaal Benno , McGaugh James L. 
Published: March 2003

AbstractGlucocorticoid‐induced memory enhancement is known to depend on β‐adrenoceptor activation in the basolateral amygdala (BLA). Additionally, inactivation of muscarinic cholinergic receptors in the rat amygdala blocks memory enhancement induced by concurrent β‐adrenergic activation. Together, these findings suggest that glucocorticoid‐induced modulation of memory consolidation requires cholinergic as well as adrenergic activation in the BLA. Two experiments investigated this issue. The first experiment examined whether blockade of muscarinic cholinergic receptors in the BLA with atropine alters the memory‐enhancing effects of the systemically administered glucocorticoid dexamethasone. Dexamethasone (0.3, 1.0 or 3.0 mg/kg, s.c.) administered to rats immediately after inhibitory avoidance training produced dose‐dependent enhancement of 48‐h retention. Concurrent bilateral infusions of the muscarinic cholinergic antagonist atropine (0.5 μg in 0.2 μL per side) into the BLA blocked the memory enhancement. The second experiment investigated whether the BLA is a locus of interaction between glucocorticoid and muscarinic activation. The specific glucocorticoid receptor (GR or type II) agonist RU 28362 (1.0, 3.0 or 10 ng) was infused into the BLA either alone or together with atropine immediately after training. The GR agonist produced dose‐dependent memory enhancement and atropine blocked the memory enhancement. These findings indicate that muscarinic cholinergic activation within the BLA is critical for enabling glucocorticoid enhancement of memory consolidation and that enhancement of memory induced by GR activation in the BLA requires cholinergic activation within the BLA.
Role of the GABAA receptor γ2 subunit in the development of gonadotropin‐releasing hormone neurons in vivo
Authors: Simonian Sharon X. , Skynner Michael J. , Sieghart Werner , Essrich Christian , Luscher Bernhard , Herbison Allan E. 
Published: March 2003

AbstractWe have employed transgenic mouse models to examine the functional significance of the γ2 subunit of the GABAA (γ‐aminobutyric acid) receptor to the correct development of gonadotropin‐releasing hormone (GnRH) neurons in vivo. In the first experiment, the expression of γ2 subunit protein by the GnRH phenotype was determined using transgenic mice in which GnRH gene sequences direct the expression of the LacZ reporter to the nucleus of the GnRH neurons. This greatly facilitates the immunocytochemical identification of non‐nuclear‐located antigens within GnRH neurons and revealed that ∼ 25% of juvenile GnRH neurons were immunoreactive for the γ2 subunit and that this increased to 40% in pubertal mice. In the second experiment, GnRH mRNA expression was examined in the brains of γ2 subunit knockout mice (γ20/0) and their wild‐type (γ2+/+) littermates at embryonic day 15 and postnatal days (P) 0 and 11–16 using in situ hybridization. The distribution and numbers of cells expressing GnRH mRNA in γ2+/+ and γ20/0 mice were not found to differ at any age. However, the GnRH mRNA content of medial septal cells was significantly lower in γ20/0 compared with γ2+/+ mice at P11–16 (P < 0.05) and the same trend was observed for preoptic area neurons. These results demonstrate that while the γ2 subunit of the GABAA receptor is expressed by postnatal GnRH neurons, their embryonic development does not require a functional γ2 subunit. In contrast, postnatal GnRH mRNA expression was found to be dependent upon signalling through the GABAA receptor.
Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain
Authors: Acarin Laia , González Berta , Castellano Bernardo 
Published: March 2003

AbstractCytokines are important intercellular messengers involved in neuron–glia interactions and in the microglial‐astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N‐methyl‐d‐aspartate in postnatal day 9 rats, and the cytokines interleukin‐1 beta (IL‐1β), interleukin‐6 (IL‐6), tumour necrosis factor alpha (TNFα) and transforming growth factor beta 1 (TGF‐β1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine‐expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL‐6 and downregulation of TNFα and TGF‐β1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL‐6, TNFα and TGF‐β1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL‐1β and TNFα expression, were the earliest glial cells producing cytokines, at 2–10 h postinjection. Later on, cytokine‐positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFα and IL‐6, and microglia/macrophages showed mild IL‐1β and TGF‐β1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.
Attempted endogenous tissue repair following experimental spinal cord injury in the rat: involvement of cell adhesion molecules L1 and NCAM?
Authors: Brook Gary A. , Houweling Diane A. , Gieling Roben G. , Hermanns Thomas , Joosten Elbert A. J. , Bär Dop P. R. , Gispen Willem‐Hendrik , Schmitt Andreas B. , Leprince P. , Noth Johannes , Nacimiento Wilhelm 
Published: March 2003

AbstractIt is widely accepted that the devastating consequences of spinal cord injury are due to the failure of lesioned CNS axons to regenerate. The current study of the spontaneous tissue repair processes following dorsal hemisection of the adult rat spinal cord demonstrates a phase of rapid and substantial nerve fibre in‐growth into the lesion that was derived largely from both rostral and caudal spinal tissues. The response was characterized by increasing numbers of axons traversing the clearly defined interface between the lesion and the adjacent intact spinal cord, beginning by 5 days post operation (p.o.). Having penetrated the lesion, axons became associated with a framework of NGFr‐positive non‐neuronal cells (Schwann cells and leptomeningeal cells). Surprisingly few of these axons were derived from CGRP‐ or SP‐immunoreactive dorsal root ganglion neurons. At the longest survival time (56 days p.o.), there was a marked shift in the overall orientation of fibres from a largely rostro‐caudal to a dorso‐ventral axis. Attempts to identify which recognition molecules may be important for these re‐organizational processes during attempted tissue repair demonstrated the widespread and intense expression of the cell adhesion molecules (CAM) L1 and N‐CAM. Double immunofluorescence suggested that both Schwann cells and leptomeningeal cells contributed to the pattern of CAM expression associated with the cellular framework within the lesion.
Schizophrenia: glutathione deficit in cerebrospinal fluid and prefrontal cortex in vivo
Authors: Do K. Q. , Trabesinger A. H. , Kirsten‐Krüger M. , Lauer C. J. , Dydak U. , Hell D. , Holsboer F. , Boesiger P. , Cuénod M. 
Published: March 2003

AbstractSchizophrenia is a major psychiatric disease, which affects the centre of the personality, with severe problems of perception, cognition as well as affective and social behaviour. In cerebrospinal fluid of drug‐free schizophrenic patients, a significant decrease in the level of total glutathione (GSH) by 27% (P < 0.05) was observed as compared to controls, in keeping with the reported reduced level of its metabolite γ‐glutamylglutamine. With a new non‐invasive proton magnetic resonance spectroscopy methodology, GSH level in medial prefrontal cortex of schizophrenic patients was found to be 52% (P = 0.0012) lower than in controls. GSH plays a fundamental role in protecting cells from damage by reactive oxygen species generated among others by the metabolism of dopamine. A deficit in GSH would lead to degenerative processes in the surrounding of dopaminergic terminals resulting in loss of connectivity. GSH also potentiates the N‐methyl‐d‐aspartate (NMDA) receptor response to glutamate, an effect presumably reduced by a GSH deficit, leading to a situation similar to the application of phencyclidine (PCP). Thus, a GSH hypothesis might integrate many established biological aspects of schizophrenia.
Developmental regulation of neurogenesis in the pluripotent human embryonal carcinoma cell line NTERA‐2
Authors: Przyborski S. A. , Morton I. E. , Wood A. , Andrews P. W. 
Published: March 2003

AbstractEmbryonal carcinoma (EC) cells provide a caricature of pluripotent embryonic stem (ES) cells and may be used as surrogates for investigating the mechanisms that regulate cell differentiation during embryonic development. NTERA‐2 is a human EC cell line that differentiates in response to retinoic acid yielding cells that include terminally differentiated neurons. The expression of genes known to be involved in the formation of the vertebrate nervous system was examined during retinoic acid‐induced NTERA‐2 differentiation. Differentiation of these human EC cells into neurons could be divided into three sequential phases. During phase 1, in the first week of differentiation, hath1 mRNA showed a small transient increase that correlated with the rapid accumulation of nestin message, a marker of neuroprogenitors. Transcripts of nestin were quickly downregulated during phase 2 as expression of neuroD1, characteristic of neuroprogenitors exiting the cell cycle, was induced. A neural cell surface antigen, detected by the monoclonal antibody A2B5, was expressed by cells exiting the cell cycle, correlating with the expression of neuroD1 as the cells became post‐mitotic. Markers of mature neural cells (e.g. synaptophysin and neuron‐specific enolase) were subsequently increased during phase 3 and were maintained. This regulated pattern of gene expression and commitment to the neural lineage indicates that differentiation of NTERA‐2 neurons in vitro follows a similar pathway to that observed by neural ectodermal precursors during vertebrate neurogenesis in vivo.
Maternal deprivation affects behaviour from youth to senescence: amplification of individual differences in spatial learning and memory in senescent Brown Norway rats
Authors: Oitzl Melly S. , Workel Judith O. , Fluttert Marc , Frösch Fawzia , De Kloet E. Ron 
Published: March 2003

AbstractPrevious studies have shown that deprivation of the infant rat from maternal care has pronounced effects on the stress system during ontogeny. Here we test the hypothesis that 24 h of maternal deprivation at postnatal day 3 will cause persistent changes in behaviour. Spatial learning and memory of male Brown Norway rats deprived as infants were observed in the Morris water maze at 3, 12, 24 and 30–32 months of age (young, adult, aged, senescent). Their nondeprived mother‐reared littermates served as controls. (i) With increasing age, water maze performance declined in deprived and nondeprived groups. However, once the task was learned the animals maintained their good performance during retest at later ages. (ii) Maternal deprivation delayed acquisition until adulthood and caused at every age a higher degree of persistent behaviour as judged from the performance of deprived rats' free swim trials and reversal trials. (iii) At senescence the mean performance in the water maze did not differ between the groups. Instead, the individual performance was strikingly different within each group. Senescent deprived rats were either nonimpaired or impaired with only a few animals showing an intermediate performance. Thus, a large group of animals (≈ 40%) ages successfully as they are resistant to the effect of maternal deprivation. In contrast, the majority of the control animals displayed intermediate performance. Taken together, maternal deprivation has life‐long consequences for behaviour and culminates at senescence in amplification of individual differences in learning ability rather than in a generalized deterioration of cognitive functions.
Representation of accuracy in the dorsal premotor cortex
Authors: Gomez Jose E. , Fu Qinggong , Flament Didier , Ebner Timothy J. 
Published: March 2003

AbstractThe endpoint accuracy of a reaching movement strongly affects kinematics, particularly during the final phases of movement. However, where and how accuracy is represented in the central nervous system remains unknown. In this study, the discharge of 150 neurons located primarily in the dorsal premotor cortex (PMd), were recorded from monkeys performing an instructed delay, centre‐out reaching task in which movement direction and target size were systematically varied. Linear regression analyses were used to assess the dependence of movement kinematics and cell discharge on target direction, size and tangential velocity (i.e. speed). The speed and timing of the movement were dependent on both direction and target size. Initially direction was the dominant predictor whilst target size became more important as the hand reached the target. A temporal multiple linear regression analysis found significant correlations with target size in 99 of 150 cells. The discharge of 134 cells was directionally tuned and 83 cells modulated with mean speed. Significant correlations of discharge with target size occurred throughout the task as did correlations with direction. However, correlations with direction preferentially occurred early in the task, prior to movement onset, whilst correlations with target size tended to occur late, well after movement onset. This temporal dependency of the firing in relationship to target direction and size mirrored that observed for the kinematics. We conclude that the discharge of PMd cells is highly correlated with the accuracy requirement of the movement. The timing of the correlations suggest that accuracy information is available for the planning and for the on‐line control of endpoint accuracy.
Inward current responses to urinary substances in rat vomeronasal sensory neurons
Authors: Inamura Kouhei , Kashiwayanagi Makoto 
Published: March 2003

AbstractNo study has yet demonstrated an inward current in response to pheromonal substances in vomeronasal sensory neurons. Using female rat vomeronasal sensory neurons, we here successfully recorded inward currents in response to urine from various sources. Of the neurons that responded to urine, 77% responded to only one type of urine. Male Wistar urine induced responses preferentially in the apical layer of the sensory epithelium, whilst male Donryu and female Wistar urine induced responses mainly in the basal layer of the epithelium. The amplitude of inward currents induced by application of male Wistar urine was voltage‐dependent with average amplitude of −47.1 ± 6.2 pA at −74 mV. The average reversal potential for male Wistar urine was −9.3 ± 6.1 mV, which was not apparently different from the reversal potentials for urine from different species. It is likely that the urine‐induced inward currents in response to different types of urine are mediated via a similar channel. The simultaneous removal of Na+ and Ca2+ from extracellular solution eliminated the response. The magnitude of the urine‐induced inward current in Cl–‐free external solution was similar to that in normal solution, suggesting that the urine‐induced current is cation selective. Removal of external Ca2+ enhanced the amplitude of the urine‐induced current and prolonged the response. Application of the constant‐field equation indicated a very high permeability coefficient for Ca2+. This study first demonstrated that substances contained in urine elicited inward currents, which induce an excitatory response in vomeronasal sensory neurons, through cation‐selective channels.