bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular expression of connexins in the rat brain: neuronal localization, effects of kainate‐induced seizures and expression in apoptotic neuronal cells
Authors: Condorelli Daniele F. , Trovato‐Salinaro Angela , Mudò Giuseppa , Mirone Melita B. , Belluardo Natale 
Published: October 2003

AbstractThe identification of connexins (Cxs) expressed in neuronal cells represents a crucial step for understanding the direct communication between neurons and between neuron and glia. In the present work, using a double‐labelling method combining in situ hybridization for Cx mRNAs with immunohistochemical detection for neuronal markers, we provide evidence that, among cerebral connexins (Cx26, Cx32, Cx36, Cx37, Cx40, Cx43, Cx45 and Cx47), only Cx45 and Cx36 mRNAs are localized in neuronal cells in both developing and adult rat brain. In order to establish whether connexin expression is influenced in vivo by abnormal neuronal activity, we examined the short‐term effects of kainate‐induced seizures. The results revealed an unexpected expression of Cx26 and Cx45 mRNA in neuronal cells undergoing apoptotic cell death in the CA3–CA4, in the hilus of the hippocampus and in other brain regions involved in seizure‐induced lesion. However, the expression of Cx26 and Cx45 mRNAs was not associated with detectable expression of corresponding proteins as evaluated by immunohistochemistry with specific antibodies. Moreover, in the same brain regions Cx32 and Cx43 were up‐regulated in non‐neruronal cells whereas the neuronal Cx36 was down‐regulated. Taken together the present results provide novel information regarding the specific subpopulation of neurons expressing Cx45 and raise the question of the meaning of connexin mRNA expression in the neuronal apoptotic process.
Increased neurogenesis and brain‐derived neurotrophic factor in neurokinin‐1 receptor gene knockout mice
Authors: Morcuende Sara , Gadd Christopher A. , Peters Marco , Moss Andrew , Harris Elizabeth A. , Sheasby Anne , Fisher Amy S. , De Felipe Carmen , Mantyh Patrick W. , Rupniak Nadia M. J. , Giese K. Peter , Hunt Stephen P. 
Published: October 2003

AbstractIt has previously been shown that chronic treatment with antidepressant drugs increases neurogenesis and levels of brain‐derived neurotrophic factor in the hippocampus. These changes have been correlated with changes in learning and long‐term potentiation and may contribute to the therapeutic efficacy of antidepressant drug treatment. Recently, antagonists at the neurokinin‐1 receptor, the preferred receptor for the neuropeptide substance P, have been shown to have antidepressant activity. Mice with disruption of the neurokinin‐1 receptor gene are remarkably similar both behaviourally and neurochemically to mice maintained chronically on antidepressant drugs. We demonstrate here that there is a significant elevation of neurogenesis but not cell survival in the hippocampus of neurokinin‐1 receptor knockout mice. Neurogenesis can be increased in wild‐type but not neurokinin‐1 receptor knockout mice by chronic treatment with antidepressant drugs which preferentially target noradrenergic and serotonergic pathways. Hippocampal levels of brain‐derived neurotrophic factor are also two‐fold higher in neurokinin‐1 receptor knockout mice, whereas cortical levels are similar. Finally, we examined hippocampus‐dependent learning and memory but found no clear enhancement in neurokinin‐1 receptor knockout mice. These data argue against a simple correlation between increased levels of neurogenesis or brain‐derived neurotrophic factor and mnemonic processes in the absence of increased cell survival. They support the hypothesis that increased neurogenesis, perhaps accompanied by higher levels of brain‐derived neurotrophic factor, may contribute to the efficacy of antidepressant drug therapy.
Distribution of α‐ and γ‐synucleins in the adult rat brain and their modification by high‐dose cocaine treatment
Authors: Brenz Verca Maria S. , Bahi Amine , Boyer Frederic , Wagner George C. , Dreyer Jean‐Luc 
Published: October 2003

AbstractSynucleins have attracted much attention because of their involvement in several neurodegenerative disorders. In a screening for genes differentially expressed after high‐dose cocaine exposure, we found γ‐synuclein as a major upregulated candidate in the tegmentum. Overexpression of both α‐ and γ‐synuclein after drug treatment was confirmed by means of microarrays, yielding an increase in the hippocampus, the striatum and the tegmentum (2.65 ×, 1.96 × and 3.5 ×, respectively, for α‐synuclein vs. 2.7 ×, 1.96 × and 7.16 × for γ‐synuclein), but no change in the nucleus accumbens. Investigation of the distribution of mRNA (byin situhybridization) and of the proteins (by immunocytochemistry) shows in both cases a clearly distinct pattern of expression for α‐ and γ‐synuclein. α‐synuclein displays a very characteristic distribution, confined to specific nuclei, whereas γ‐synuclein is more widely expressed throughout the brain. mRNA of both α‐ and γ‐synucleins display a complementary pattern of expression all over the cortex. In contrast to γ‐synuclein, α‐synuclein is neuronal, being only found in NeuN‐expressing cells, and is expressed in the basal ganglia (faintly) and in the substantia nigra compacta where it is highly correlated with tyrosine hydroxylase. Immunocytochemistry shows that γ‐synuclein generally colocalizes with glial fibrillary acidic protein‐expressing cells and is abundant in the red nucleus, the substantia nigra reticulata and the anterior commissure, while γ‐synuclein mRNA labels the matrix compartments of the caudate‐putamen. The role of synucleins in relation to cocaine‐induced plasticity or neurotoxicity is discussed.
Expression of PRiMA in the mouse brain: membrane anchoring and accumulation of ‘tailed’ acetylcholinesterase
Authors: Perrier Noël A. , Khérif Sonia , Perrier Anselme L. , Dumas Sylvie , Mallet Jacques , Massoulié Jean 
Published: October 2003

AbstractWe analysed the expression of PRiMA (proline‐rich membrane anchor), the membrane anchor of acetylcholinesterase (AChE), by in situ hybridization in the mouse brain. We compared the pattern of PRiMA transcripts with that of AChE transcripts, as well as those of choline acetyltransferase and M1 muscarinic receptors which are considered pre‐ and postsynaptic cholinergic markers. We also analysed cholinesterase activity and its molecular forms in several brain structures. The results suggest that PRiMA expression is predominantly or exclusively related to the cholinergic system and that anchoring of cholinesterases to cell membranes by PRiMA represents a limiting factor for production of the AChE tailed splice variant (AChET)–PRiMA complex, which represents the major AChE component in the brain. This enzyme species is mostly associated with cholinergic neurons because the pattern of PRiMA mRNA expression largely coincides with that of ChAT. We also show that, in both mouse and human, PRiMA proteins exist as two alternative splice variants which differ in their cytoplasmic regions.
Taste‐olfactory convergence, and the representation of the pleasantness of flavour, in the human brain
Authors: De Araujo Ivan E. T. , Rolls Edmund T. , Kringelbach Morten L. , McGlone Francis , Phillips Nicola 
Published: October 2003

AbstractThe functional architecture of the central taste and olfactory systems in primates provides evidence that the convergence of taste and smell information onto single neurons is realized in the caudal orbitofrontal cortex (and immediately adjacent agranular insula). These higher‐order association cortical areas thus support flavour processing. Much less is known, however, about homologous regions in the human cortex, or how taste–odour interactions, and thus flavour perception, are implemented in the human brain. We performed an event‐related fMRI study to investigate where in the human brain these interactions between taste and odour stimuli (administered retronasally) may be realized. The brain regions that were activated by both taste and smell included parts of the caudal orbitofrontal cortex, amygdala, insular cortex and adjoining areas, and anterior cingulate cortex. It was shown that a small part of the anterior (putatively agranular) insula responds to unimodal taste and to unimodal olfactory stimuli, and that a part of the anterior frontal operculum is a unimodal taste area (putatively primary taste cortex) not activated by olfactory stimuli. Activations to combined olfactory and taste stimuli where there was little or no activation to either alone (providing positive evidence for interactions between the olfactory and taste inputs) were found in a lateral anterior part of the orbitofrontal cortex. Correlations with consonance ratings for the smell and taste combinations, and for their pleasantness, were found in a medial anterior part of the orbitofrontal cortex. These results provide evidence on the neural substrate for the convergence of taste and olfactory stimuli to produce flavour in humans, and where the pleasantness of flavour is represented in the human brain.
5‐HT1A receptors are involved in short‐ and long‐term processes responsible for 5‐HT‐induced locomotor function recovery in chronic spinal rat
Authors: Antri M. , Mouffle C. , Orsal D. , Barthe J.‐Y. 
Published: October 2003

AbstractAfter thoracic spinal cord transection, a paraplegic syndrome occurs. Previous data showed that an acute administration of a 5‐HT2 agonist (quipazine) could promote motor function recovery in spinal rats. However, continuous subdural perfusion of quipazine via an osmotic pump over 1 month proved to be more effective. The present study was designed to investigate the possible involvement of 5‐HT1A receptors in such recovery. Motor performances and locomotor parameters were analysed in spinal animals receiving daily, for 1 month, a dose of the 5‐HT1A agonist 8‐OHDPAT. The results were compared to those obtained in spinal rats receiving either a placebo or quipazine in the same conditions. Using daily injections instead of continuous perfusion of either receptor agonist to spinal animals allowed characterization of short‐ and long‐term consequences of pharmacological stimulation of 5‐HT1A and 5‐HT2 receptors on motor function recovery. Our data demonstrate that daily injections of a 5‐HT1A agonist induce long‐term, cumulative, positive effects on motor function recovery, as assessed by the improvement in the walking parameters observed before the ‘day‐test’ injection. This might involve use‐dependent processes depending on a chronic and/or repetitive stimulation of the spinal network for locomotion in relation to 5‐HT receptor activation. A further improvement in the motor parameters, transiently observed following the injection, suggests a more direct action of 5‐HT1A and 5‐HT2 receptor activation on spinal neurons involved in motor pattern generation.
Neurons of the rat preoptic area and the raphe pallidus nucleus innervating the brown adipose tissue express the prostaglandin E receptor subtype EP3
Authors: Yoshida Kyoko , Nakamura Kazuhiro , Matsumura Kiyoshi , Kanosue Kazuyuki , König Matthias , Thiel Heinz‐Jürgen , Boldogköi Zsolt , Toth Ida , Roth Joachim , Gerstberger Rüdiger , Hübschle Thomas 
Published: October 2003

AbstractThe major effector organ for thermogenesis during inflammation or experimental pyrogen‐induced fever in rodents is the brown adipose tissue (BAT). Prostaglandin E2 (PGE2) microinjection into the medial preoptic area (POA) of rats leads to hyperthermia through an increase in BAT thermogenesis and induces pyrogenic signal transmission towards the raphe pallidus nucleus (RPa), a brainstem nucleus known to contain sympathetic premotor neurons for BAT control. The medial POA has a high expression of prostaglandin E receptor subtype EP3 (EP3R) on POA neurons, suggesting that these EP3R are main central targets of PGE2 to mediate BAT thermogenesis. To reveal central command neurons that contain EP3R and polysynaptically project to the BAT, we combined EP3R immunohistochemistry with the detection of transneuronally labelled neurons that were infected after injection of pseudorabies virus into the BAT. Neurons double‐labelled with EP3R and viral surface antigens were particularly numerous in two brain regions, the medial POA and the RPa. Of all medial POA neurons that became virally infected 71 h after BAT inoculation, about 40% expressed the EP3R. This subpopulation of POA neurons is the origin of a complete neuronal chain that connects potential PGE2‐sensitive POA neurons with the BAT. As for the efferent pathway of pyrogenic signal transmission, we hypothesize that neurons of this subpopulation of EP3R expressing POA neurons convey their pyrogenic signals towards the BAT via the RPa. We additionally observed that two‐thirds of those RPa neurons that polysynaptically project to the interscapular BAT also expressed the EP3R, suggesting that RPa neurons themselves might possess prostaglandin sensitivity that is able to modulate BAT thermogenesis under febrile conditions.
Postsynaptic contributions to hippocampal network hyperexcitability induced by chronic activity blockade in vivo
Authors: Galvan Cynthia D. , Wenzel Jurgen H. , Dineley Kelly T. , Lam Trang T. , Schwartzkroin Philip A. , Sweatt J. David , Swann John W. 
Published: October 2003

AbstractNeuronal activity is thought to play an important role in refining patterns of synaptic connectivity during development and in the molecular maturation of synapses. In experiments reported here, a 2‐week infusion of tetrodotoxin (TTX) into rat hippocampus beginning on postnatal day 12 produced abnormal synchronized network discharges in in vitro slices. Discharges recorded upon TTX washout were called ‘minibursts’, owing to their small amplitude. They were routinely recorded in area CA3 and abolished by CNQX, an AMPA receptor antagonist. Because recurrent excitatory axon collaterals remodel and glutamate receptor subunit composition changes after postnatal day 12, experiments examined possible TTX‐induced alterations in recurrent excitation that could be responsible for network hyperexcitability. In biocytin‐labelled pyramidal cells, recurrent axon arbors were neither longer nor more highly branched in the TTX infusion site compared with saline‐infused controls. However, varicosity size and density were increased. Whereas most varicosities contained synaptophysin and synaptic vesicles, many were not adjacent to postsynaptic specializations, and thus failed to form anatomically identifiable synapses. An increased pattern of excitatory connectivity does not appear to explain network hyperexcitability. Quantitative immunoblots also indicated that presynaptic markers were unaltered in the TTX infusion site. However, the postsynaptic AMPA and NMDA receptor subunits, GluR1, NR1 and NR2B, were increased. In electrophysiological studies EPSPs recorded in slices from TTX‐infused hippocampus had an enhanced sensitivity to the NR2B containing NMDA receptor antagonist, ifenprodil. Thus, increases in subunit protein result in alterations in the composition of synaptic NMDA receptors. Postsynaptic changes are likely to be the major contributors to the hippocampal network hyperexcitability and should enhance both excitatory synaptic efficacy and plasticity.
The cerebellum and spatial ability: dissection of motor and cognitive components with a mouse model system
Authors: Martin Loren A. , Goldowitz Dan , Mittleman Guy 
Published: October 2003

AbstractThe cerebellum has recently been linked to spatial navigation, as indicated by the inferior performance of cerebellar mutant or cerebellar lesioned animals in the water maze. The inability to dissociate motor from cognitive deficits in the impaired water maze performance has been a confounding variable in previous studies, however. In this study, we sought to define clearly the role of the cerebellar system in spatial navigation outside of motor control by creating a mouse model of Purkinje cell loss with intact motor ability, and testing these mice in the water maze. To this end, we made aggregation chimeras between Lc/+ mice, which lose all Purkinje cells postnatally, and +/+ control mice. Lc/+ mice are ataxic and show impaired rotor‐rod performance. By contrast, we show that Lc/+ ⇆ +/+ chimeras above a threshold of Purkinje cell loss show no outward signs of motor impairment and demonstrated normal rotor‐rod ability. In the water maze, we found that Lc/+ mice showed impaired performance in the place, cue and platform removal tasks, whereas Lc/+⇆+/+ chimeras performed similarly to controls in all tasks. We found that the impaired performance in the water maze of Lc/+ mice resulted from both motor as well as cognitive impairment that could be separated from one another by statistical means. In addition, through the analysis of individual chimeric mice, the relationships between these deficits and the total number of Purkinje cells were determined and a specific role for Purkinje cells in search strategy was identified.
Distinct subtypes of group I metabotropic glutamate receptors on rat spinal neurons mediate complex facilitatory and inhibitory effects
Authors: Marchetti Cristina , Taccola Giuliano , Nistri Andrea 
Published: October 2003

AbstractWhile group I glutamate metabotropic (mGlu) receptors show discrete neuronal distribution in the neonatal rat spinal cord, the functional role of their distinct receptor subtypes remains uncertain. Intracellular recording from lumbar motoneurons together with extracellular recording of ventral root (VR) responses was used to investigate the differential contribution by mGlu receptor subtypes to cell excitability and network activity. The group I agonist DHPG evoked motoneuron depolarization (via the AIDA or CPCCOEt‐sensitive mGlu receptor subtype 1) mainly at network level and generated sustained, network‐dependent oscillations (via the MPEP‐sensitive mGlu receptor subtype 5). DHPG also decreased the peak amplitude of synaptic responses induced by dorsal root stimuli, an effect unrelated to depolarization and dependent on glycinergic transmission. Synaptic responses were insensitive to AIDA or MPEP. The present results can be explained by assuming excitation of discrete classes of interneurons by group I mGlu receptor activity. Thus, the cellular distribution of those mGlu receptors at strategic circuit connections may determine the functional outcome of the network in terms of excitation or inhibition. Even if there was insufficient activation by endogenous glutamate of mGlu receptors during synaptic activity evoked by DR stimuli, it is apparent that such receptors are important pharmacological targets for powerful and rapid up‐ or down‐regulation of spinal signal processing at network level, providing a rationale for the proposed use of mGlu receptor agonists in a variety of spinal pathological conditions.
Subthalamic stimulation influences postmovement cortical somatosensory processing in Parkinson's disease
Authors: Devos D. , Labyt E. , Cassim F. , Bourriez J. L. , Reyns N. , Touzet G. , Blond S. , Guieu J. D. , Derambure P. , Destée A. , Defebvre L. 
Published: October 2003

AbstractIn Parkinson's disease, poor motor performance (resulting primarily from abnormal cortical activation during movement preparation and execution) may also be due to impaired sensorimotor integration and defective cortical activity termination of the ongoing movement, thus delaying preparation of the following one. Reduced movement‐related synchronization of the beta rhythm in Parkinson's disease compared to controls has been put forward as evidence for impaired postmovement cortical deactivation. We assessed the effects of subthalamic deep brain stimulation and l‐dopa on beta rhythm synchronization over the premotor and primary sensorimotor cortex. Ten advanced patients performed self‐paced wrist flexion in four conditions according to the presence or not of stimulation and l‐dopa. Compared to without treatment, the motor score improved by ≈ 60%; the beta synchronization was present over the contralateral frontocentral region and increased significantly over the contralateral central region under stimulation and under l‐dopa, with a maximal effect when both treatments were associated. Our advanced patients displayed very focused and attenuated beta rhythm synchronization which, under stimulation, increased over the contralateral premotor and primary sensorimotor cortex. Stimulation and l‐dopa both partly restored postmovement cortical deactivation in advanced Parkinson's disease, although the respective mechanisms probably differ. They may improve bradykinesia and cortical deactivation by reestablishing movement‐related somatosensory processing at the end of the movement through the basal ganglia into the cortex.
Recombinant AAV‐mediated expression of galanin in rat hippocampus suppresses seizure development
Authors: Lin En‐Ju D. , Richichi Cristina , Young Deborah , Baer Kristin , Vezzani Annamaria , During Matthew J. 
Published: October 2003

AbstractGalanin, a 29‐ or 30‐amino acid neuropeptide, has been implicated in the modulation of seizures. In this study, we constructed a recombinant adeno‐associated viral (AAV) vector to constitutively over‐express galanin (AAV‐GAL). The vector mediated efficient transduction of HEK 293 cells in vitro and robust galanin expression in vivo when injected into the rat dorsal hippocampus. Rats were administered kainic acid intrahippocampally 2.5 months following AAV‐GAL or empty vector (AAV‐Empty) injection to study the effect of vector‐mediated galanin over‐expression on seizures. AAV‐GAL‐injected rats showed a decreased number of seizure episodes and total time spent in seizures compared to AAV‐Empty rats, despite similar latencies to development of the first EEG seizure and similar levels of neuronal damage in the CA3 region for both groups. These data show that recombinant AAV mediates strong and stable over‐expression of galanin when injected into the rat hippocampus resulting in a significant anticonvulsive effect. The seizure suppression effect of galanin expression in the hippocampus by viral vectors may lead to novel therapeutic strategies for the treatment and management of intractable seizures with focal onset such as temporal lobe epilepsy.