Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several isoenzymes of the Na(+),K(+)-ATPase are expressed in brain but their specific roles are poorly understood. Recently, it was suggested that an isoenzyme of the Na(+),K(+)-ATPase containing the alpha(2) subunit, together with the glutamate transporters GLAST and GLT-1, participate in a coupling mechanism between neuronal activity and energy metabolism taking place in astrocytes. To substantiate this hypothesis, we compared the distribution of alpha(2), GLAST and/or GLT-1 in the rat cerebral cortex using double immunofluorescence and confocal microscopy, and immunocytochemistry at the electron microscopic level. We also investigated the relationship between alpha(2), GLAST or GLT-1 and asymmetrical synaptic junctions (largely glutamatergic) and GABAergic nerve terminals. Results show that the alpha(2) subunit has an exclusive astroglial localization, and that it is almost completely co-distributed with GLAST and GLT-1 when evaluated by confocal microscopy. This similar distribution was confirmed at the ultrastructural level, which further showed that the vast majority of the alpha(2) staining (73% of all labelled elements), like that of GLAST and GLT-1, was located in glial leaflets surrounding dendritic spines and the dendritic and/or axonal elements of asymmetrical (glutamatergic) axo-dendritic synapses. Synapses ensheathed by alpha(2), GLAST or GLT-1 virtually never included (<or=2%) GABAergic nerve terminals or synaptic junctions. However, a subset of GABAergic nerve terminals (10-14%) were directly apposed to asymmetrical axo-dendritic junctions surrounded by alpha(2), GLAST or GLT-1. Altogether these results demonstrate that alpha(2), GLAST and GLT-1 have comparable perisynaptic distribution within cortical astrocytes most likely associated with glutamatergic synapses.
Cereb Cortex 2002 May
PMID:Similar perisynaptic glial localization for the Na+,K+-ATPase alpha 2 subunit and the glutamate transporters GLAST and GLT-1 in the rat somatosensory cortex. 1195 Jul 69

Neurons in the rat cerebral cortex are enriched in group I metabotropic glutamate receptor (mGluR) subtypes and respond to their activation during development. To understand better the mechanisms by which mGluR1 and mGluR5 mediate these effects, the goal of this study was to elucidate the expression pattern and to determine the cellular and the precise subcellular localization of these two receptor subtypes in the rat neocortex and hippocampus during late prenatal and postnatal development. At the light microscopic level, mGluR1alpha and mGluR5 were first detected in the cerebral cortex with different expression levels at embryonic day E18. Thus, mGluR5 had a moderate expression, whereas mGluR1alpha was detected as a diffuse and weak labeling. mGluR5 was localized in some Cajal- Retzius cells as well as in other cell types, such as pioneer neurons of the marginal zone. During postnatal development, the distribution of the receptors dramatically changed. From P0 to around P10, mGluR1alpha was localized in identified, transient Cajal-Retzius cells of neocortex and hippocampus, until these cells disappear. In addition, a population of interneurons localized the receptor from the second/third postnatal week. In contrast, mGluR5 was localized mainly in pyramidal cells and in some interneurons, with a neuropilar staining throughout the cerebral cortex. At the electron microscopic level, the immunoreactivity for both group I mGluR subtypes was expressed postsynaptically. Using immunogold methods, mGluR1alpha and mGluR5 immunoreactivities were found throughout postnatal development at the edge of postsynaptic specialization of asymmetrical synapses. These results show that the two group I mGluRs have a differential expression pattern in neocortex and hippocampus that may suggest roles for the receptors in the early processing of cortical information and in the control of cortical developmental events.
Cereb Cortex 2002 Jun
PMID:Differential distribution of group I metabotropic glutamate receptors during rat cortical development. 1200 62

The establishment of the adult pattern of neocortical circuitry depends on various intrinsic and extrinsic factors, whose modification during development can lead to alterations in cortical organization and function. We report the effect of 16 days of spaceflight [Neurolab mission; from postnatal day 14 (P14) to P30] on the neocortical representation of the hindlimb synaptic circuitry in rats. As a result, we show, for the first time, that development in microgravity leads to changes in the number and morphology of cortical synapses in a laminar-specific manner. In the layers II/III and Va, the synaptic cross-sectional lengths were significantly larger in flight animals than in ground control animals. Flight animals also showed significantly lower synaptic densities in layers II/III, IV and Va. The greatest difference was found in layer II/III, where there was a difference of 344 million synapses per mm(3) (15.6% decrease). Furthermore, after a 4 month period of re-adaptation to terrestrial gravity, some changes disappeared (i.e. the alterations were transient), while conversely, some new differences also appeared. For example, significant differences in synaptic density in layers II/III and Va after re-adaptation were no longer observed, whereas in layer IV the density of synapses increased notably in flight animals (a difference of 185 million synapses per mm(3) or 13.4%). In addition, all the changes observed only affected asymmetrical synapses, which are known to be excitatory. These results indicates that terrestrial gravity is a necessary environmental parameter for normal cortical synaptogenesis. These findings are fundamental in planning future long-term spaceflights.
Cereb Cortex 2002 Aug
PMID:Spaceflight induces changes in the synaptic circuitry of the postnatal developing neocortex. 1212 37

The uncinate fasciculus interconnects the anterior temporal and inferior frontal lobes. The temporal lobes show a number of anatomical asymmetries, some of which are altered in schizophrenia. This study was performed to assess the size and symmetry of the uncinate fasciculus in normal subjects and in patients with the disorder. The area, fibre density and total fibre number of left and right uncinate fasciculi were estimated using stereological methods in 21 control subjects and 17 schizophrenics. The uncinate fasciculus was found to be asymmetrical in both sexes, being 27% larger and containing 33% more fibres in the right than the left hemisphere. Of the 25 brains from which both hemispheres were available, the size asymmetry was seen in 20 subjects and the greater number of fibres in 21 subjects. There was no significant effect of schizophrenia upon the uncinate fasiculus, nor interactions of diagnosis with side or sex. We conclude that the uncinate fasciculus is larger in the right hemisphere, perhaps indicating greater right-sided fronto-temporal connectivity. The unchanged size of the fasciculus in schizophrenia contrasts with commissural tracts, which are affected in this brain series in a sex-specific manner.
Cereb Cortex 2002 Nov
PMID:Asymmetry of the uncinate fasciculus: a post-mortem study of normal subjects and patients with schizophrenia. 1237 10

The human striatum is functionally organized into limbic, associative, and sensorimotor subdivisions, which process information related to emotional, cognitive, and motor function. Dopamine projections ascending from the midbrain provide important modulatory input to these striatal subregions. The aim of this study was to compare activation of dopamine D2 receptors after amphetamine administration in the functional subdivisions of the human striatum. D2 receptor availability (V3") was measured with positron emission tomography and [11C]raclopride in 14 healthy volunteers under control conditions and after the intravenous administration of amphetamine (0.3 mg/kg). For each condition, [11C]raclopride was administered as a priming bolus followed by constant infusion, and measurements of D2 receptor availability were obtained under sustained binding equilibrium conditions. Amphetamine induced a significantly larger reduction in D2 receptor availability (DeltaV3") in limbic (ventral striatum, -15.3 +/- 11.8%) and sensorimotor (postcommissural putamen, -16.1 +/- 9.6%) regions compared with associative regions (caudate and precommissural putamen, -8.1 +/- 7.2%). Results of this region-of-interest analysis were confirmed by a voxel-based analysis. Correction for the partial volume effect showed even greater differences in DeltaV3" between limbic (-17.8 +/- 13.8%), sensorimotor (-16.6 +/- 9.9%), and associative regions (-7.5 +/- 7.5%). The increase in euphoria reported by subjects after amphetamine was associated with larger DeltaV3" in the limbic and sensorimotor regions, but not in the associative regions. These results show significant differences in the dopamine response to amphetamine between the functional subdivisions of the human striatum. The mechanisms potentially accounting for these regional differences in amphetamine-induced dopamine release within the striatum remain to be elucidated, but may be related to the asymmetrical feed-forward influences mediating the integration of limbic, cognitive, and sensorimotor striatal function via dopamine cell territories in the ventral midbrain.
J Cereb Blood Flow Metab 2003 Mar
PMID:Imaging human mesolimbic dopamine transmission with positron emission tomography. Part II: amphetamine-induced dopamine release in the functional subdivisions of the striatum. 1262 4

We determined the degree to which the response modulation of macaque inferior temporal (IT) neurons corresponds to perceptual versus physical shape similarities. IT neurons were tested with four groups of shapes. One group consisted of variations of simple, symmetrical (i.e. regular) shapes that differed in nonaccidental properties (NAPs, i.e. viewpoint-invariant), such as curved versus straight contours. The second and third groups were composed of, respectively, simple and complex asymmetrical (i.e. irregular) shapes, all with curved contours. A fourth group consisted of simple, asymmetrical shapes, but with straight (corners) instead of curved contours. The neural modulations were greater for the shapes differing in NAPs than for the shapes differing in the configuration of the convexities and concavities. Multidimensional scaling showed that a population code of the neural activity could readily distinguish the four shape groups. This pattern of neural modulation was strongly manifested in the results of a sorting task by human subjects but could not be predicted using current image-based models (i.e. pixel energies, V1-like Gabor-jet filtering and HMAX). The representation of shape in IT thus exceeds a mere faithful representation of physical reality, by emphasizing perceptually salient features relevant for essential categorizations.
Cereb Cortex 2005 Sep
PMID:Representation of regular and irregular shapes in macaque inferotemporal cortex. 1561 28

Repetitive bimanual finger-tapping movements tend toward mirror symmetry: There is a spontaneous transition from less stable asymmetrical movement patterns to more stable symmetrical ones under frequency stress but not vice versa. During this phase transition, the interaction between the signals controlling each hand (cross talk) is expected to be prominent. To depict the regions of the brain in which cortical cross talk occurs during bimanual coordination, we conducted event-related functional magnetic resonance imaging using a bimanual repetitive-tapping task. Transition-related activity was found in the following areas: the bilateral ventral premotor cortex, inferior frontal gyrus, middle frontal gyrus, inferior parietal lobule, insula, and thalamus; the right rostral portion of the dorsal premotor cortex and midbrain; the left cerebellum; and the presupplementary motor area, rostral cingulate zone, and corpus callosum. These regions were discrete from those activated by bimanual movement execution. The phase-transition-related activation was right lateralized in the prefrontal, premotor, and parietal regions. These findings suggest that the cortical neural cross talk occurs in the distributed networks upstream of the primary motor cortex through asymmetric interhemispheric interaction.
Cereb Cortex 2006 Sep
PMID:Neural correlates of the spontaneous phase transition during bimanual coordination. 1630 23

Callosal dysgenesis (CD) is observed in many neurodevelopmental conditions, but its subjacent mechanisms are unknown, despite extensive research on animals. Here we employ magnetic resonance diffusion tensor imaging and tractography in human CD to reveal the aberrant circuitry of these brains. We searched particularly for evidence of plasticity. Four main findings are described--1) in the presence of a callosal remnant or a hypoplastic corpus callosum (CC), fibers therein largely connect the expected neocortical regions; 2) callosal remnants and hypoplastic CCs display a fiber topography similar to normal; 3) at least 2 long abnormal tracts are formed in patients with defective CC: the well-known Probst bundle (PB) and a so far unknown sigmoid, asymmetrical aberrant bundle connecting the frontal lobe with the contralateral occipitoparietal cortex; and 4) whereas the PB is topographically organized and has an ipsilateral U-connectivity, the sigmoid bundle is a long, heterotopic commissural tract. These observations suggest that when the developing human brain is confronted with factors that hamper CC fibers to cross the midline, some properties of the miswired fibers are maintained (such as side-by-side topography), whereas others are dramatically changed, leading to the formation of grossly abnormal white matter tracts.
Cereb Cortex 2007 Mar
PMID:Neuroplasticity in human callosal dysgenesis: a diffusion tensor imaging study. 1662 61

The mediodorsal nuclei of thalamus (MD), prefrontal cortex (PFC), and nucleus accumbens core (NAc) form an interconnected network that may work together to subserve certain forms of behavioral flexibility. The present study investigated the functional interactions between these regions during performance of a cross-maze-based strategy set-shifting task. In Experiment 1, reversible bilateral inactivation of the MD via infusions of bupivacaine did not impair simple discrimination learning, but did disrupt shifting from response to visual cue discrimination strategy, and vice versa. This impairment was due to an increase in perseverative errors. In Experiment 2, asymmetrical disconnection inactivations of the MD on one side of the brain and PFC on the other also caused a perseverative deficit when rats were required to shift from a response to a visual cue discrimination strategy, as did disconnections between the PFC and the NAc. However, inactivation of the MD on one side of the brain and the NAc contralaterally resulted in a selective increase in never-reinforced errors, suggesting this pathway is important for eliminating inappropriate strategies during set shifting. These data indicate that set shifting is mediated by a distributed neural circuit, with separate neural pathways contributing dissociable components to this type of behavioral flexibility.
Cereb Cortex 2007 Jul
PMID:Thalamic-prefrontal cortical-ventral striatal circuitry mediates dissociable components of strategy set shifting. 1696 18

Chronic impairment of forelimb and digit movement is a common problem after stroke that is resistant to therapy. Although in the last years some studies have been performed to increase the efficacy of rehabilitative experience and training, the pharmacological approaches in this context remain poorly developed. We decided to study the effect of a chronic treatment with CDP-choline, a safe and well-tolerated drug that is known to stabilize membranes, on functional outcome and neuromorphological changes after stroke. To assess the functional recovery we have performed the staircase reaching test and the elevated body swing test (EBST), for studying sensorimotor integration and asymmetrical motor function respectively. The treatment with CDP-choline, initiated 24 h after the middle cerebral artery occlusion (MCAO) and maintained during 28 days, improved the functional outcome in both the staircase test (MCAO+CDP=87.0+/-6.6% pellets eaten vs. MCAO+SAL=40.0+/-4.5%; p<0.05) and the EBST (MCAO+CDP=70.0+/-6.8% vs. MCAO+SAL=88.0+/-5.4%; contralateral swing p<0.05). In addition, to study potential neuronal substrates of the improved function, we examined the dendritic morphology of layer V pyramidal cells in the undamaged motor cortex using a Golgi-Cox procedure. The animals treated with CDP-choline showed enhanced dendritic complexity and spine density compared with saline group. Our results suggest that a chronic treatment with CDP-choline initiated 24 h after the insult is able to increase the neuronal plasticity within noninjured and functionally connected brain regions as well as to promote functional recovery.
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PMID:A chronic treatment with CDP-choline improves functional recovery and increases neuronal plasticity after experimental stroke. 1723 23


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