bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systemic administration of the propargylamine CGP 3466B prevents behavioural and morphological deficits in rats with 6‐hydroxydopamine‐induced lesions in the substantia nigra
Authors: Andringa G. , Van Oosten R. V. , Unger W. , Hafmans T. G. M. , Veening J. , Stoof J. C. , Cools A. R. 
Published: March 2003

AbstractThe ability of CGP 3466B to attenuate the behavioural and morphological consequences of experimentally induced cell death was investigated in a recently updated animal model of Parkinson's disease. 6‐Hydroxydopamine was infused bilaterally into the substantia nigra pars compacta of rats that were pretreated with desimipramine. Treatment with CGP 3466B (0.0014–1.4 mg/kg, injected subcutaneously) or its solvent was begun 2 h after the 6‐OHDA injection, and maintained twice daily for 14 days. After a washout period of 14 days, changes in motor behaviour were evaluated, using the open field test (analysis of normal and abnormal stepping, e.g.) and the paw test (analysis of retraction time of limbs). Changes in learning and memory were evaluated with the help of the Morris water maze task. Following immunocytochemical staining of tyrosine hydroxylase, the extent of the lesion was quantified using a computerized system. CGP 3466B prevented all deficits produced by 6‐hydroxydopamine (6‐OHDA), though at different doses. It prevented: abnormal stepping (0.0014–0.014 mg/kg); increased forelimb and hindlimb retraction time (0.014–0.14 mg/kg and 0.0014–0.14 mg/kg, respectively); delayed learning (1.4 mg/kg); and reduced tyrosine hydroxylase immunoreactivity in the substantia nigra (0.0014–0.014 mg/kg). CGP 3466B (0.0014–0.14 mg/kg) induced no deficits in sham‐treated rats. CGP 3466B (1.4 mg/kg), however, did not show any benefit on motor deficits in 6‐OHDA‐lesioned rats, and induced abnormal movements and decreased the tyrosine hydroxylase immunoreactivity in the substantia nigra pars compacta and the ventral tegmental area of sham‐lesioned animals. It is concluded that CGP 3466B prevents all 6‐OHDA‐induced behavioural and immunocytochemical deficits, though at different doses. CGP 3466B is suggested to be a valuable agent for inhibiting the dopaminergic degeneration in patients with Parkinson's disease.
Ipsilateral involvement of primary motor cortex during motor imagery
Authors: Porro Carlo A. , Cettolo Valentina , Francescato Maria Pia , Baraldi Patrizia 
Published: March 2003

AbstractTo investigate whether motor imagery involves ipsilateral cortical regions, we studied haemodynamic changes in portions of the motor cortex of 14 right‐handed volunteers during actual motor performance (MP) and kinesthetic motor imagery (MI) of simple sequences of unilateral left or right finger movements, using functional magnetic resonance imaging (fMRI). Increases in mean normalized fMRI signal intensities over values obtained during the control (visual imagery) task were found during both MP and MI in the posterior part of the precentral gyrus and supplementary motor area, both on the contralateral and ipsilateral hemispheres. In the left lateral premotor cortex, fMRI signals were increased during imagery of either left or right finger movements. Ipsilateral cortical clusters displaying fMRI signal changes during both MP and MI were identified by correlation analyses in 10 out of 14 subjects; their extent was larger in the left hemisphere. A larger cortical population involved during both contralateral MP and MI was found in all subjects. The overall spatial extent of both the contralateral and the ipsilateral MP + MI clusters was ∼ 90% of the whole cortical volume activated during MP. These results suggest that overlapping neural networks in motor and premotor cortex of the contralateral and ipsilateral hemispheres are involved during imagery and execution of simple motor tasks.
Increased acetylcholine release in the rat medial prefrontal cortex during performance of a visual attentional task
Authors: Passetti F. , Dalley J. W. , O'connell M. T. , Everitt B. J. , Robbins T. W. 
Published: March 2003

AbstractRecent studies have suggested a functional link between cortical cholinergic output and attentional task demands, whereby acetylcholine (ACh) release is regulated according to the outcome of ongoing behaviour. To explore this hypothesis we measured ACh efflux in the rat medial prefrontal cortex (mPFC) during between‐session manipulations of the cognitive demands of an attentional task. Rats were trained to detect visual stimuli in a five‐choice serial reaction time task (5‐CSRTT) which involves sustained and divided attention. Following habituation to tethering and implantation with a microdialysis probe in the mPFC, rats were tested in the 5‐CSRTT for three consecutive days, with different lengths of stimulus duration. During performance of the 5‐CSRTT we measured robust, reproducible, task‐related increases in ACh release in the mPFC across all sessions. Variations of the stimulus duration from the standard 0.5 s resulted in the predicted behavioural effects (reductions and increases in choice accuracy with 0.25 s and 5 s, respectively), but there was no evidence of either greater changes in ACh release in the more demanding condition or smaller changes in the less demanding condition. By contrast, in the session with 5‐s stimulus duration there was a positive correlation between prefrontal cortical ACh efflux and the total number of trials completed. In summary, the present study shows that ACh efflux in the rat mPFC is increased during performance of a 5‐CSRTT, but has found no evidence to support a specific relationship between cholinergic cortical output and attentional performance.
Galanin‐R1 and ‐R2 receptor mRNA expression during the development of rat brain suggests differential subtype involvement in synaptic transmission and plasticity
Authors: Burazin Tanya C. D. , Larm Jari A. , Ryan Mary C. , Gundlach Andrew L. 
Published: March 2003

AbstractThe present study employed 35S‐labelled oligonucleotides and in situ hybridization to examine the distribution in the developing rat brain of mRNA encoding two galanin receptor subtypes, i.e. Gal‐R1 and Gal‐R2. Gal‐R1 and/or Gal‐R2 mRNA was detected at embryonic day (E) 20 and from postnatal day (P) 0–70. Gal‐R1 mRNA was highly expressed in olfactory regions, ventral hippocampal CA fields, dorsomedial thalamic areas and many hypothalamic nuclei at all ages studied. In adult brain, Gal‐R2 mRNA was most abundant in the dentate gyrus, anterior and posterior hypothalamus, raphe and spinal trigeminal nuclei, and in the dorsal motor nucleus of the vagus. At P0–P7, Gal‐R2 mRNA was more widely distributed and abundant than at other ages, with highest levels of expression detected throughout the neocortex and thalamus. Thus, Gal‐R2 transcripts had a more restricted distribution than Gal‐R1 and were differentially abundant at different ages, while the distribution and relative abundance of Gal‐R1 mRNA did not alter substantially during postnatal development. In general, Gal‐R1 and ‐R2 mRNAs were localized in regions previously shown to contain [125I]‐galanin binding sites and galanin‐positive terminals in adult brain. Galanin‐immunostaining was assessed in postnatal brain to determine whether peptide innervation correlated with observed transient receptor expression, but was not particularly enriched in Gal‐R2 mRNA‐positive areas of P4 or P7 brain. These results, together with earlier findings [e.g. Burazin, T. C. D. & Gundlach, A. L. (1998) J. Neurochem., 71, 879–882], suggest that Gal‐R1 receptors have a broad role in normal synaptic transmission, while Gal‐R2 receptors, in addition to a similar role in particular pathways, may be involved in processes prominent during the establishment and maturation of synaptic connections in developing brain and during neural damage and repair in the mature nervous system.
Gluco‐ and mineralocorticoid receptor‐mediated regulation of neurotrophic factor gene expression in the dorsal hippocampus and the neocortex of the rat
Authors: Hansson Anita C. , Cintra Antonio , Belluardo Natale , Sommer Wolfgang , Bhatnagar Maheep , Bader Michael , Ganten Detlev , Fuxe Kjell 
Published: March 2003

AbstractGluco‐ and mineralocorticoid receptors (GR and MR) act via common promoter elements but may exert different effects on gene regulation in various regions of the forebrain. In order to separately analyse the role of GR and MR in the regulation of neurotrophic factor genes and their receptors, we used adrenalectomy and subsequent hormone injections in the rat as a model system. Twenty‐four hours after adrenalectomy rats were injected with a single dose of corticosterone (2 and 10 mg/kg), aldosterone (0.5 mg/kg) or the synthetic glucocorticoid agonist RU 28362 (4 mg/kg). Gene expression of basic fibroblast growth factor (bFGF) and its high‐affinity receptors [fibroblast growth factor receptor subtypes 1–3 (FGF‐R1, FGF‐R2, FGF‐R3)], as well as brain‐derived growth factor (BDNF) and neurotrophin‐3 (NT‐3) was analysed at 4 h after the hormone injection in CA1–CA4 (cornus of Ammon areas of the hippocampus) and dentate gyrus of the dorsal hippocampus and in neocortex by means of in situ hybridization. We found that bFGF is regulated in CA2, CA3 and dentate gyrus by GR and MR together, and in CA1, CA4 and neocortex by GR alone. FGF‐R2 expression in the hippocampus seems to be regulated only by MR, while BDNF expression appears to depend on both receptors. FGF‐R1, FGF‐R3 and NT‐3 were only moderately affected by the hormone activation of GR and MR acting in concert or alone in the various regions. Thus, the present findings suggest that the adrenal cortical system through GR and MR participate in the control of neurotrophic factor signalling in a highly subregion‐ and cellular‐dependent manner.
Implication of Bcl‐2 and Caspase‐3 in age‐related Purkinje cell death in murine organotypic culture: an in vitro model to study apoptosis
Authors: Ghoumari Abdel M. , Wehrlé Rosine , Bernard Ora , Sotelo Constantino , Dusart Isabelle 
Published: March 2003

AbstractNeuronal cell death is an essential feature of nervous system development and neurodegenerative diseases. Most Purkinje cells in murine cerebellar organotypic culture die when taken from 1–5‐day‐old mice (P1–P5), whereas they survive when taken before or after these ages. Using DNA gel electrophoresis, terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling (TUNEL) and electron microscopic analyses, we were able to show that this massive Purkinje cell death is apoptotic in nature and reaches a peak at P3. From the several endogenous genes known to be involved in the apoptotic process, we have focused on two: the bcl‐2 and the caspase‐3 that encode for anti‐apoptotic and pro‐apoptotic proteins, respectively. Immunostaining for activated Caspase‐3 correlated with Purkinje cell death. A better survival of Purkinje cells was observed in P3 slices taken from hu‐bcl‐2 transgenic mice, and in slices treated with z‐DEVD.fmk (an inhibitor of numerous caspases). Thus, these two genes are implicated in the age‐related Purkinje cell apoptosis in organotypic culture. As Purkinje cell death in vitro takes place at the same age as Purkinje cells engaged in intense synaptogenesis and dendritic remodeling in vivo, we propose that this apoptosis reflects a naturally occurring Purkinje cell death during this critical period.
The basolateral amygdala complex is involved with, but is not necessary for, rapid acquisition of Pavlovian ‘fear conditioning’
Authors: Cahill Larry , Vazdarjanova Almira , Setlow Barry 
Published: March 2003

AbstractA major hypothesis about lateral/basolateral amygdala complex (BLC) function in memory proposes that the BLC is the site where conditioned stimulus–unconditioned stimulus (CS–US) associations are formed and permanently stored during Pavlovian ‘fear conditioning.’ Thus, according to this hypothesis, the BLC is necessary for the acquisition and expression of both discrete‐cue and contextual Pavlovian fear conditioning. This hypothesis clearly requires that animals with complete lesions of the BLC be completely unable to acquire Pavlovian fear conditioning. In this experiment, distribution of training and testing trials over three sessions revealed that rats with complete BLC lesions rapidly acquired a contextual CS–US association (as assessed with freezing behaviour), although their performance, as expected, did not equal that of sham operated controls. Irrespective of the nature of the freezing deficit relative to controls, the learning in the BLC‐lesioned rats strongly indicates that Pavlovian fear conditioning CS–US associations can be rapidly acquired in the absence of the BLC, and that the BLC cannot therefore be necessary for their acquisition.
Plateau potential‐dependent windup of the response to primary afferent stimuli in rat dorsal horn neurons
Authors: Morisset Valérie , Nagy Frédéric 
Published: March 2003

AbstractIn the spinal cord, repetitive stimulation of nociceptive afferent fibres induces a progressive build‐up of dorsal horn neuron (DHN) responses. This ‘action potential windup’ is used as a cellular model of central sensitization to pain. It partly relies on synaptic plasticity, being reduced after blocking NMDA and neurokinin receptors. Using intracellular recordings in a slice preparation of the rat spinal cord, we have analysed the implication of an additional non‐synaptic component of windup. Primary afferent fibres were electrically stimulated in the dorsal root. Of 47 responding deep DHNs, 17 (36%) produced action potential windup and afterdischarge during consecutive periods of repeated stimuli (0.4–1 Hz) activating high‐ (n = 13 neurons) and low‐threshold (n = 6 neurons) afferent fibres. When the NMDA receptors were blocked, the rate of windup did not change. In all neurons, there was an absolute correlation between expression of windup and the production of calcium‐dependent plateau potentials. Sensitization of the DHN response, similar to the synaptically induced windup, was obtained by repetitive intracellular injection of depolarizing current pulses. This intracellularly induced windup had the same pharmacology as the plateau potential. Synaptically induced windup was also abolished by nifedipine, an L‐type calcium‐channel blocker. Expression of plateau properties in DHNs is therefore a critical component of windup, operating downstream of synaptic processes. Being associated with calcium influx, generation of plateau potentials could be a link between short‐term plasticity and the long‐term modification of DHN excitability associated with central sensitization.
Blockade of the NMDA receptor increases developmental apoptotic elimination of granule neurons and activates caspases in the rat cerebellum
Authors: Monti Barbara , Contestabile Antonio 
Published: March 2003

AbstractElimination of neurons produced in excess naturally occurs during brain development through programmed cell death. Among the many survival factors affecting this process, a role for neurotransmitters acting on specific receptors has been suggested. We have performed an in vivo pharmacological blockade of the N‐methyl‐ d‐aspartate (NMDA) subtype of glutamate receptors, using the competitive NMDA receptor antagonist CGP 39551 at developmental stages corresponding to those at which a survival dependence on the stimulation of this receptor has been demonstrated for cerebellar granule neurons explanted in culture (typically from postnatal day 7 to postnatal day 11 or 13). We were able to demonstrate an increased level of DNA fragmentation in the cerebellum of the treated rats. At the P11 stage, in particular, the fragmented DNA extracted from the cerebellum of CGP 39551‐treated pups showed a clear laddering of nucleosomal fragments after agarose‐gel electrophoresis. Accordingly, in situ TUNEL technique showed a remarkable increase of cells positive for nucleosomal DNA fragmentation, particularly in the inner granular layer of the cerebellum of treated rats at P11 stage. Therefore, the natural rate of apoptotic elimination of cerebellar granule neurons is considerably enhanced under conditions of pharmacological blockade of the NMDA receptor, thus demonstrating, for the first time in vivo, a clear survival dependence of these neurons upon the stimulation of the NMDA receptor. Concomitantly with the increased rate of apoptotic elimination of granule neurons, the activity of two death proteases of the caspase family, in particular of caspase 3 and caspase 1 at a lower extent, was remarkably increased in the cerebellum of the treated rats. On the contrary, a marker related to the normal differentiation process of granule neurons, the enzyme ornithine decarboxylase, was strongly decreased in its activity in the cerebellum of treated rat pups.
Role played by sodium in activity‐dependent secretion of neurotrophins − revisited
Authors: Hoener M. C. 
Published: March 2003

AbstractIn previous experiments, a causal relationship between sodium influx and secretion of nerve growth factor (NGF) was deduced from the observation that the sodium substitute N‐methyl‐ d‐glucamine (NMDG) abolished any activity‐mediated NGF secretion that depends on intact internal calcium stores. However, all available experimental evidence speaks against sodium‐mediated calcium mobilization from these stores under physiological conditions. We now report that rapid sodium influx initiated by monensin or ouabain did not induce brain‐derived neurotrophic factor (BDNF) secretion from either native hippocampal slices or BDNF‐transduced hippocampal neuronal cultures. Additionally, we found marked differences between the replacement of sodium by NMDG and sucrose on the one hand, and choline and lithium on the other. Replacement of 100% (and as little as 10%) sodium by NMDG or sucrose not only blocked the activity‐mediated neurotrophin secretion, but itself led to a rapid and substantial increase of neurotrophin secretion. In contrast, the replacement of sodium (10% and 100%) by lithium and choline did not result in a release of neurotrophins, and only 100% replacement blocked the activity‐mediated neurotrophin secretion. We conclude that the blocking effects of NMDG and sucrose on neurotrophin secretion do not reflect the sodium replacement, but instead represent an independent blocking effect. These differences were also reflected in part by electrophysiological investigations in individually patched hippocampal neurons. The importance of the present observations lies not only in the reevaluation of the involvement of sodium in activity‐dependent neurotrophin secretion, but also in the demonstration that sodium replacement may initiate ‘side effects’ that are unrelated to sodium replacement.
Regulation of hippocampal cell adhesion molecules NCAM and L1 by contextual fear conditioning is dependent upon time and stressor intensity
Authors: Merino J. Joaquín , Cordero M. Isabel , Sandi Carmen 
Published: March 2003

AbstractCell adhesion molecules (CAMs) of the immunoglobulin superfamily, NCAM and L1, as well as the post‐translational addition of α‐2,8‐linked polysialic acid (PSA) homopolymers to NCAM (PSA–NCAM), have been implicated in the neural mechanisms underlying memory formation. Given that the degree of stress elicited by the training situation is one of the key factors that influence consolidation processes, this study questioned whether training rats under different stressor intensities (0.2, 0.4, or 1 mA shock intensity) in a contextual fear conditioning task might regulate subsequent expression of NCAM, PSA–NCAM and L1 in the hippocampus, as evaluated immediately after testing rats for conditioning at 12 and 24 h after training. Behavioural inhibition (evaluated as a ‘freezing’ index) at testing and post‐testing plasma corticosterone levels were also assessed. The results showed that 12 h post‐training, conditioned animals displayed reduced NCAM, but increased L1, expression. At this time point, the group trained at the highest shock intensity (1 mA) also presented decreased PSA–NCAM expression. Analyses performed 24 h post‐training indicated that the 1 mA group exhibited increased NCAM and L1 expression, but decreased expression of PSA–NCAM levels. In addition, L1 values that presented a shock intensity‐dependent U‐shaped pattern were also increased in the group trained at the lowest shock condition (0.2 mA) and remained unchanged in the intermediate shock condition (0.4 mA). Freezing and corticosterone values at both testing times were positively related with shock intensity experienced at training. Therefore, our results show a complex regulation of CAMs of the immunoglobulin superfamily in the hippocampus that depends upon stressor intensity and time factors. In addition, the pattern of CAMs expression found in the 1 mA group (which is the one that shows higher post‐training corticosterone levels and develops the stronger and longer‐lasting levels of fear conditioning) supports the view that, after a first phase of synaptic de‐adherence during consolidation, NCAM and L1 might participate in the stabilization of selected synapses underlying the establishment of long‐term memory for contextual fear conditioning, and suggests that glucocorticoids might play a role in the observed regulation of CAMs.
Alleviation of overtraining reversal effect by transient inactivation of the dorsal striatum
Authors: Van Golf Racht‐Delatour B. , Massioui N. El 
Published: March 2003

AbstractIn this study, we investigated the role of the dorsal striatum in the acquisition and the use (retrieval) of a specific learning developed during overtraining. The paradigm was such that rats had to respond differentially to two signals in order to obtain food or to avoid an electrical footshock. Overtraining was aimed at eliciting a facilitative effect on discrimination reversal as compared to simply trained rats. In this way, transient inactivation of the dorsal striatum by lidocaine enabled us to investigate, separately, the role of this structure during overtraining and reversal. The data show that inactivating the dorsal striatum before each reversal session prevented the overtraining reversal effect observed in control rats. Moreover, inactivation of the dorsal striatum during overtraining had no effect on the level of discriminative performance just as it did not affect the subsequent facilitative effect on reversal. These results show that even though the striatum might normally be part of a routine automatic system, clearly its contribution is not essential. Indeed, despite inactivation of the striatum in overtrained rats, their ability to develop an efficient selection process that can be used during reversal was observed. However, the integrity of the striatum became essential in order to mediate the modification of behaviour when this behavioural routine formed during overtraining had to be modified during reversal.