bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protracted expression of serotonin transporter and altered thalamocortical projections in the barrelfield of hypothyroid rats
Authors: Ausó Eva , Cases Olivier , Fouquet Coralie , Camacho Miguel , García‐Velasco José‐Victor , Gaspar Patricia , Berbel Pere 
Published: March 2003

AbstractIn humans, thyroid hormone deficiency during development causes severe neurological diseases but the underlying mechanisms are unclear. We have examined the effects of thyroid hormones on the development of somatosensory thalamocortical projections, by inducing hypothyroidism in rats by methimazole treatment at embryonic day 13 and subsequent thyroidectomy at postnatal day 6 (P6). Initial development of the thalamocortical projections and their tangential and laminar patterning were similar in normal and hypothyroid rats from birth to P4. The tangential spread of the thalamocortical arbors is reduced in hypothyroid rats after P4, paralleling the overall cortical atrophy. Anterograde tracing and single axon reconstructions indicate that thalamic afferents reached layer IV but that they had fewer and shorter branches, with a 42% reduction in the number of boutons. The transient serotonin (5‐HT) immunostaining and 5‐HT transporter (5‐HTT) expression were both prolonged by 5 days in hypothyroid rats. This does not reflect a delayed maturation of the thalamus because other transiently expressed genes such as the vesicular monoamine transporter and the 5‐HT1B receptor are not modified. Protracted 5‐HTT expression also occurred in other areas with transient expression, but no changes were observed in the raphe nuclei where the 5‐HTT is expressed permanently. Thus, thyroid hormones appear to be important in regulating the extinction of the 5‐HTT in nonserotoninergic neurons. The transient stabilization of 5‐HT reuptake in hypothyroid rats could affect the growth of thalamic axons. Our data stress the importance of maternal and foetal thyroid hormones for the normal development of sensory systems.
Selective cardiorespiratory and catecholaminergic areas express the hypoxia‐inducible factor‐1α (HIF‐1α) under in vivo hypoxia in rat brainstem
Authors: Pascual Olivier , Denavit‐Saubié Monique , Dumas Sylvie , Kietzmann Thomas , Ghilini Ginette , Mallet Jacques , Pequignot Jean‐Marc 
Published: March 2003

AbstractUnder severe oxygen deprivation, all cells are able to express the transcription factor HIF‐1, which activates a wide range of genes. Under tolerable hypoxia, chemosensory inputs are integrated in brainstem areas, which control cardiorespiratory responses. However, the molecular mechanisms of this functional acclimatization are unknown. We investigated when and where the inducible HIF‐1α subunit is expressed in the rat brainstem in vivo, under physiological hypoxia. The regional localization of HIF‐1α mRNA and protein was determined by in situ hybridization and immunocytochemistry in adult male rats exposed to moderate hypoxia (10% O2) for 1–6 h. HIF‐1α protein was found in cell types identified by immunocytochemistry as catecholaminergic neurons. Hypoxia induced HIF‐1α mRNA and protein in only some parts of the brainstem located dorsomedially and ventrolaterally, which are those involved in the cardiorespiratory control. No labelling was detected under normoxia. The protein was detected in glia and neurons after 1 and 6 h of hypoxia, respectively. A subset of A2C2 and A1C1 catecholaminergic neurons colocalized tyrosine hydroxylase and HIF‐1α proteins under hypoxia, but no HIF‐1α was detected in more rostral catecholaminergic areas. In contrast to cardiorespiratory areas, HIF‐1α protein was already present under normoxia in glial cells of brainstem tracts but was not overexpressed under hypoxia, although HIF‐1α mRNA was up‐regulated. In conclusion, there appear to be two regulatory mechanisms for HIF‐1α expression in the brainstem: hypoxic induction of HIF‐1α protein in cardiorespiratory‐related areas and constitutive protein expression unaffected by hypoxia in brainstem tracts.
Steroid structure and pharmacological properties determine the anti‐amnesic effects of pregnenolone sulphate in the passive avoidance task in rats
Authors: Vallée M. , Shen W. , Heinrichs S. C. , Zorumski C. F. , Covey D. F. , Koob G. F. , Purdy R. H. 
Published: March 2003

AbstractPregnenolone sulphate (PREGS) has generated interest as one of the most potent memory‐enhancing neurosteroids to be examined in rodent learning studies, with particular importance in the ageing process. The mechanism by which this endogenous steroid enhances memory formation is hypothesized to involve actions on glutamatergic and GABAergic systems. This hypothesis stems from findings that PREGS is a potent positive modulator of N‐methyl‐d‐aspartate receptors (NMDARs) and a negative modulator of γ‐aminobutyric acidA receptors (GABAARs). Moreover, PREGS is able to reverse the amnesic‐like effects of NMDAR and GABAAR ligands. To investigate this hypothesis, the present study in rats examined the memory‐altering abilities of structural analogs of PREGS, which differ in their modulation of NMDAR and/or GABAAR function. The analogs tested were: 11‐ketopregnenolone sulphate (an agent that is inactive at GABAARs and NMDARs), epipregnanolone ([3β‐hydroxy‐5β‐pregnan‐20‐one] sulphate, an inhibitor of both GABAARs and NMDARs), and a newly synthesized (–) PREGS enantiomer (which is identical to PREGS in effects on GABAARs and NMDARs). The memory‐enhancing effects of PREGS and its analogs were tested in the passive avoidance task using the model of scopolamine‐induced amnesia. Both PREGS and its (–) enantiomer blocked the effects of scopolamine. The results show that, unlike PREGS, 11‐ketopregnenolone sulphate and epipregnanolone sulphate failed to block the effect of scopolamine, suggesting that altering the modulation of NMDA receptors diminishes the memory‐enhancing effects of PREGS. Moreover, enantioselectivity was demonstrated by the ability of natural PREGS to be an order of magnitude more effective than its synthetic enantiomer in reversing scopolamine‐induced amnesia. These results identify a novel neuropharmacological site for the modulation of memory processes by neuroactive steroids.
Seizure‐induced gene expression in area CA1 of the mouse hippocampus
Authors: French P. J. , O'Connor V. , Voss K. , Stean T. , Hunt S. P. , Bliss T. V. P. 
Published: March 2003

AbstractSynaptic plasticity in the hippocampus requires activity‐dependent gene expression. We have therefore profiled gene expression in area CA1 following the induction of an electroshock‐evoked maximal seizure. Using cDNA microarrays, the differential expression of ≈ 9000 cDNAs was examined. In situ hybridization on 14 transcripts that showed strongest modulation in the microarray screen (1.8–2‐fold) confirmed the differential expression of a single gene that encodes for the nuclear hormone receptor NGFI‐B (Nur77, N10). Although this gene is only modestly up‐regulated (≈ 2‐fold) in area CA1, in situ hybridization revealed that maximal seizures induce a marked (≈ 12‐fold) up‐regulation of NGFI‐B in the dentate gyrus. These data support the notion [French et al. (2001) Eur. J. Neurosci., 13, 968–976] that CA1 pyramidal neurons are more refractory than granule cells of the dentate gyrus with respect to activity‐dependent gene transcription. Furthermore, our results argue against a large cohort of activity‐dependent genes in area CA1.
Cerebellar contribution to spatial event processing: involvement in procedural and working memory components
Authors: Mandolesi L. , Leggio M. G. , Graziano A. , Neri P. , Petrosini L. 
Published: March 2003

AbstractSpatial function is one of the cognitive functions altered in the presence of cerebellar lesions. We investigated the cerebellar contribution to the acquisition of spatial procedural and working memory components by means of a radial maze. To establish whether a cerebellar lesion would cause a deficit in solving the radial maze, a first experiment was carried out by using a full‐baited maze procedure in different experimental groups, with or without cerebellar lesion and with or without pretraining. Non‐pretrained hemicerebellectomized (HCbed) animals exhibited impaired performances in all (motor, spatial and procedural) task aspects. Pre‐trained HCbed animals performed similarly to control animals in the task aspects linked to the processing of spatial and procedural factors. To distinguish procedural from working memory components, a forced‐choice paradigm of the radial maze was used in the second experiment. Non‐pretrained HCbed rats continued to make a lot of errors and show severe perseverative tendencies, already observed in the first experiment, supporting a specific cerebellar role in acquiring new behaviours and in modifying them in relation to the context. Interestingly, hindered from putting the acquired explorative patterns into action and compelled to use only working memory abilities, the pretrained HCbed group exhibited a dramatic worsening of performance. In conclusion, the present findings demonstrate that cerebellar damage induces a specific behaviour in radial maze tasks, characterized by an inflexible use of the procedures (if indeed any procedure was acquired before the lesion) and by a severe impairment in working memory processes.
Anti‐inflammatory antioxidants attenuate the expression of inducible nitric oxide synthase mediated by advanced glycation endproducts in murine microglia
Authors: Wong Amanda , Dukic‐Stefanovic Sladjana , Gasic‐Milenkovic Jovana , Schinzel Reinhard , Wiesinger Heinrich , Riederer Peter , Münch Gerald 
Published: March 2003

AbstractAdvanced glycation endproducts (AGEs) accumulate on long‐lived protein deposits including β‐amyloid plaques in Alzheimer's disease (AD). AGE‐modified amyloid deposits contain oxidized and nitrated proteins as markers of a chronic neuroinflammatory condition and are surrounded by activated microglial and astroglial cells. We show in this study that AGEs increase nitric oxide production by induction of the inducible nitric oxide synthase (iNOS) on the mRNA and protein level in the murine microglial cell line N‐11. Membrane permeable antioxidants including oestrogen derivatives (e.g. 17β‐oestradiol) thiol antioxidants (e.g. (R+)‐α‐lipoic acid) and Gingko biloba extract EGb 761, but not phosphodiesterase inhibitors such as propentophylline, prevent the up‐regulation of AGE‐induced iNOS expression and NO production. These results indicate that oxygen free radicals serve as second messengers in AGE‐induced pro‐inflammatory signal transduction pathways. As this pharmacological mechanism is not only relevant for Alzheimer's disease, but also for many chronic inflammatory conditions, such membrane‐permeable antioxidants could be regarded not only as antioxidant, but also as potent therapeutic anti‐inflammatory drugs.
Diversity of receptive field changes in auditory cortex during natural sleep
Authors: Edeline Jean‐Marc , Dutrieux Gérard , Manunta Yves , Hennevin Elizabeth 
Published: March 2003

AbstractTwenty years ago, the study by Livingstone and Hubel [(1981) Nature, 291, 554] was viewed as a first step toward understanding how changes in state of vigilance affect sensory processing. Since then, however, very few attempts have been made to progress in this direction. In the present study, 56 cells were recorded in the auditory cortex of adult, undrugged guinea pigs, and the frequency tuning curves were tested during continuous and stable periods of wakefulness and of slow‐wave sleep (SWS). Twelve cells were also tested during paradoxical sleep. Over the whole cell population, the reponse latency, the frequency selectivity and the size of the suprathreshold receptive field were not significantly modified during SWS compared with waking. However, this lack of global effects resulted from the heterogeneity of response changes displayed by cortical cells. During SWS, the receptive field size varied as a function of the changes in evoked responses: it was unchanged for the cells whose evoked responses were not modified (38% of the cells), reduced for the cells whose responses were decreased (48%) and enlarged for the cells whose responses were increased (14%). This profile of changes differs from the prevalent receptive field shrinkage that was observed in the auditory thalamus during SWS [Edeline et al. (2000), J. Neurophysiol.,84, 934]. It also contrasts with the receptive field enlargement that was described under anaesthesia when the EEG spontaneously shifted from a desynchronized to a synchronized pattern [Wörgötter et al. (1998), Nature,396, 165]. Reasons for these differences are discussed.
Expression of ephrin‐A2 in the superior colliculus and EphA5 in the retina following optic nerve section in adult rat
Authors: Rodger J. , Lindsey K. A. , Leaver S. G. , King C. E. , Dunlop S. A. , Beazley L. D. 
Published: March 2003

AbstractThe vertebrate retina projects topographically to visual brain centres. In the developing visual system, gradients of ephrins and Eph receptors play a role in defining topography. At maturity, ephrins but not Ephs are downregulated. Here we show that optic nerve section in adult rat differentially regulates the expression of ephrin‐A2 in the superior colliculus (SC) and of EphA5 in the retina. Expression was quantified immunohistochemically; ephrin‐A2 levels were also estimated by semiquantitative reverse transcriptase polymerase chain reaction. In the normal SC, ephrin‐A2 was expressed at low levels. At 1 month, levels of protein and of mRNA were upregulated across the contralateral SC giving rise to an increasing rostro‐caudal gradient. At 6 months, levels had fallen but a gradient remained. In the retina of normal animals, EphA5 was expressed as an increasing naso‐temporal gradient. By 1 month, expression was decreased in far temporal retina, resulting in a uniform expression across the naso‐temporal axis. We suggest that denervation‐induced plastic changes within the SC modify expression of these molecules.
Activity‐ and age‐dependent GABAergic synaptic plasticity in the developing rat hippocampus
Authors: Gubellini Paolo , Ben‐Ari Yehezkel , Gaïarsa Jean‐Luc 
Published: March 2003

AbstractActivity‐dependent plasticity of GABAergic synaptic transmission was investigated in rat hippocampal slices obtained between postnatal day (P) 0–15 using the whole‐cell patch‐clamp recording technique. Spontaneous GABAA receptor‐mediated postsynaptic currents (sGABAA‐PSCs) were isolated in the presence of ionotropic glutamate receptor antagonists. A conditioning protocol relevant to the physiological condition, consisting of repetitive depolarizing pulses (DPs) at 0.1 Hz, was able to induce long‐lasting changes in both frequency and amplitude of sGABAA‐PSCs between P0 and P8. Starting from P12, DPs were unable to induce any form of synaptic plasticity. The effects of DPs were tightly keyed to the frequency at which they were delivered. When delivered at a lower (0.05 Hz) or higher (1 Hz) frequency, DPs failed to induce any long‐lasting change in the frequency or amplitude of sGABAA‐PSCs. In two cases, DPs were able to activate sGABAA‐PSCs in previously synaptically silent cells at P0–1. These results show that long‐term changes in GABAergic synaptic activity can be induced during a restricted period of development by a conditioning protocol relevant to the physiological condition. It is suggested that such activity‐induced modifications may represent a physiological mechanism for the functional maturation of GABAergic synaptic transmission.
Impaired fear conditioning but enhanced seizure sensitivity in rats given repeated experience of withdrawal from alcohol
Authors: Stephens D. N. , Brown G. , Duka T. , Ripley T. L. 
Published: March 2003

AbstractRepeated experience of withdrawal from chronic alcohol treatment increases sensitivity to seizures. It has been argued by analogy that negative affective consequences of withdrawal also sensitize, but repeated experience of withdrawal from another sedative‐hypnotic drug, diazepam, results in amelioration of withdrawal anxiety and aversiveness. We tested whether giving rats repeated experience of withdrawal from alcohol altered their ability to acquire a conditioned emotional response (CER). Male Hooded Lister rats were fed a nutritionally complete liquid diet as their only food source. Different groups received control diet, or diet containing 7% ethanol. Rats receiving ethanol diet were fed for either 24 days (Single withdrawal, SWD), or 30 days, with two periods of 3 days, starting at day 11, and 21, in which they received control diet (Repeated withdrawal, RWD). All rats were fed lab chow at the end of their liquid diet feeding period. Starting 12 days after the final withdrawal, groups of Control, SWD and RWD rats were given pentylenetetrazole (PTZ; 30 mg/kg, i.p.) three times a week, and scored for seizures. The occurrence of two successive Stage 5 seizures was taken as the criterion for full PTZ kindling. Other groups of control, SWD and RWD rats were trained to operate levers to obtain food, and were then exposed, in a fully counterbalanced design, to light and tone stimuli which predicted unavoidable footshock (CS+), or which had no consequences (CS–). Rats consumed approximately 17.5 g/kg/day of ethanol, resulting in blood alcohol levels of approximately 100 mg/dL. Repeated administration of PTZ resulted in increasing seizure scores. RWD rats achieved kindling criterion faster than either Control or SWD rats. No differences were seen in the groups in flinch threshold to footshock (0.3 mA). At a shock intensity of 0.35 mA, Control, but not RWD or SWD rats showed significant suppression to the CS+ CS– presentation did not affect response rates. The three groups differed in their response to pairing the CS+ with increasing shock levels, the Controls remaining more sensitive to the CS+. SWD rats showed significant suppression of lever pressing during CS+ presentations only at 0.45 and 0.5 mA, and RWD rats only at 0.5 mA. Giving rats repeated experience of withdrawal from chronic ethanol results in increased sensitivity to PTZ kindling, but reduces their ability to acquire a CER. Withdrawal kindling of sensitivity to anxiogenic events does not seem to occur under circumstances which give rise to kindling of seizure sensitivity.
Estrogen and exercise interact to regulate brain‐derived neurotrophic factor mRNA and protein expression in the hippocampus
Authors: Berchtold Nicole C. , Kesslak J. Patrick , Pike Christian J. , Adlard Paul A. , Cotman Carl W. 
Published: March 2003

AbstractWe investigated the possibility that estrogen and exercise interact in the hippocampus and regulate brain‐derived neurotrophic factor (BDNF), a molecule increasingly recognized for its role in plasticity and neuron function. An important aspect of this study is to examine the effect of different time intervals between estrogen loss and estrogen replacement intervention. We demonstrate that in the intact female rat, physical activity increases hippocampal BDNF mRNA and protein levels. However, the exercise effect on BDNF up‐regulation is reduced in the absence of estrogen, in a time‐dependent manner. In addition, voluntary activity itself is stimulated by the presence of estrogen. In exercising animals, estrogen deprivation reduced voluntary activity levels, while estrogen replacement restored activity to normal levels. In sedentary animals, estrogen deprivation (ovariectomy) decreased baseline BDNF mRNA and protein, which were restored by estrogen replacement. Despite reduced activity levels in the ovariectomized condition, exercise increased BDNF mRNA levels in the hippocampus after short‐term (3 weeks) estrogen deprivation. However, long‐term estrogen‐deprivation blunted the exercise effect. After 7 weeks of estrogen deprivation, exercise alone no longer affected either BDNF mRNA or protein levels. However, exercise in combination with long‐term estrogen replacement increased BDNF protein above the effects of estrogen replacement alone. Interestingly, protein levels across all conditions correlated most closely with mRNA levels in the dentate gyrus, suggesting that expression of mRNA in this hippocampal region may be the major contributor to the hippocampal BDNF protein pool. The interaction of estrogen, physical activity and hippocampal BDNF is likely to be an important issue for maintenance of brain health, plasticity and general well‐being, particularly in women.
The voltage‐sensitive motor protein and the Ca2+‐sensitive cytoskeleton in developing rat cochlear outer hair cells
Authors: Beurg Maryline , Bouleau Yohan , Dulon Didier 
Published: March 2003

AbstractCochlear outer hair cells (OHCs) possess a unique fast voltage‐driven motility associated with a voltage‐sensitive motor protein embedded in the basolateral membrane. This mechanism is believed to underlie the cochlear amplification in mammals. OHCs also have a Ca2+/calmodulin‐dependent mechanical pathway which involves a submembranous circumferential cytoskeleton. The purpose of this study was to compare the functional appearance of the voltage‐sensitive motor proteins with that involving the Ca2+‐sensitive cytoskeleton during postnatal development of rat OHCs. We demonstrate that whole‐cell electromotility and Ca2+‐voked mechanical responses, by ionomycin, develop concomitantly after postnatal day 5 (P5). These two mechanical properties also develop simultaneously in OHCs isolated from two‐week‐old cultures of P0‐P1 organs of Corti. This excludes the participation of neural innervation in the postnatal maturation of the OHCs' motile properties. In addition, we show that the expression of the membranous voltage‐sensitive motor protein precedes, by several days, the appearance of whole‐cell electromotility. The concomitant development of whole‐cell electromotility and Ca2+‐sensitive motility, both in vivo and in vitro, underlines the cytoskeleton as an important factor in the functional organization of the voltage‐sensitive motor proteins within the plasma membrane.
AMPA receptor activation induces association of G‐beta protein with the alpha subunit of the sodium channel in neurons
Authors: Marin Philippe , Fagni Laurent , Torrens Yvette , Alcaraz Gisèle , Couraud François , Bockaert Joël , Glowinski Jacques , Prémont Joël 
Published: March 2003

AbstractGlutamatergic transmission is mediated by ionotropic receptors that directly gate cationic channels and metabotropic receptors that are coupled to second messenger generating systems and to ionic channels via heterotrimeric guanine‐nucleotide binding‐ (G) proteins. This distinction cannot be made for the ionotropic receptor subclass activated by α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid (AMPA), which has been shown to be physically associated with the α‐subunit of Gi1 protein and activates this G‐protein. Here, we report that, in addition to a Ca2+ influx, AMPA induces the mobilization of Ca2+ from the mitochondrial pool by reversing the mitochondrial Na+/Ca2+ exchanger in mouse neurons in primary culture. Both processes required the activation of tetrodotoxin‐sensitive Na+ channels. AMPA receptor activation modified the gating properties of the Na+ channel, independently of the AMPA current, suggesting a G‐protein‐mediated process. Indeed, co‐immunoprecipitation experiments indicated that AMPA receptor activation induced the association of Gβ with the α‐subunit of the Na+ channel. These results suggest that, in addition to its ionic channel function, the AMPA receptor is coupled to Na+ channels through G‐proteins and that this novel metabotropic function is involved in the control of neuronal excitability.