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Whole Brain (whole + brain)
Terms modified by Whole Brain Selected AbstractsHypofrontality in schizophrenia: a meta-analysis of functional imaging studiesACTA PSYCHIATRICA SCANDINAVICA, Issue 4 2004K. Hill Objective:, Hypofrontality is not a well-replicated finding in schizophrenia either at rest or under conditions of task activation. Method:, Studies comparing whole brain and frontal blood flow/metabolism in schizophrenic patients and normal controls were pooled. Voxel-based studies were also combined to examine the pattern of prefrontal activation in schizophrenia. Results:, Whole brain flow/metabolism was reduced in schizophrenia to only a small extent. Resting and activation frontal flow/metabolism were both reduced with a medium effect size. Duration of illness significantly moderated resting hypofrontality, but the moderating effects of neuroleptic treatment were consistent with an influence on global flow/metabolism only. Pooling of voxel-based studies did not suggest an abnormal pattern of activation in schizophrenia. Conclusion:, Meta-analysis supports resting hypofrontality in schizophrenia. Task-activated hypofrontality is also supported, but there is little from voxel-based studies to suggest that this is associated with an altered pattern of regional functional architecture. [source] Distribution and functional characterization of human Nav1.3 splice variantsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 1 2005R. Thimmapaya Abstract The focus of the present study is the molecular and functional characterization of four splice variants of the human Nav1.3 , subunit. These subtypes arise due to the use of alternative splice donor sites of exon 12, which encodes a region of the , subunit that resides in the intracellular loop between domains I and II. This region contains several important phosphorylation sites that modulate Na+ channel kinetics in related sodium channels, i.e. Nav1.2. While three of the four Nav1.3 isoforms, 12v1, 12v3 and 12v4 have been previously identified in human, 12v2 has only been reported in rat. Herein, we evaluate the distribution of these splice variants in human tissues and the functional characterization of each of these subtypes. We demonstrate by reverse transcriptase-polymerase chain reaction (RT-PCR) that each subtype is expressed in the spinal cord, thalamus, amygdala, cerebellum, adult and fetal whole brain and heart. To investigate the functional properties of these different splice variants, each , subunit isoform was cloned by RT-PCR from human fetal brain and expressed in Xenopus oocytes. Each isoform exhibited functional voltage-dependent Na+ channels with similar sensitivities to tetrodotoxin (TTX) and comparable current amplitudes. Subtle shifts in the V1/2 of activation and inactivation (2,3 mV) were observed among the four isoforms, although the functional significance of these differences remains unclear. This study has demonstrated that all four human splice variants of the Nav1.3 channel , subunit are widely expressed and generate functional TTX-sensitive Na+ channels that likely modulate cellular excitability. [source] Characterization of the quantitative trait locus for haloperidol-induced catalepsy on distal mouse chromosome 1GENES, BRAIN AND BEHAVIOR, Issue 2 2008J. R. Hofstetter We report here the confirmation of the quantitative trait locus for haloperidol-induced catalepsy on distal chromosome (Chr) 1. We determined that this quantitative trait locus was captured in the B6.D2- Mtv7a/Ty congenic mouse strain, whose introgressed genomic interval extends from approximately 169.1 to 191.3 Mb. We then constructed a group of overlapping interval-specific congenic strains to further break up the interval and remapped the locus between 177.5 and 183.4 Mb. We next queried single nucleotide polymorphism (SNP) data sets and identified three genes with nonsynonymous coding SNPs in the quantitative trait locus. We also queried two brain gene expression data sets and found five known genes in this 5.9-Mb interval that are differentially expressed in both whole brain and striatum. Three of the candidate quantitative trait genes were differentially expressed using quantitative real-time polymerase chain reaction analyses. Overall, the current study illustrates how multiple approaches, including congenic fine mapping, SNP analysis and microarray gene expression screens, can be integrated both to reduce the quantitative trait locus interval significantly and to detect promising candidate quantitative trait genes. [source] Expression of T-type calcium channel splice variants in human gliomaGLIA, Issue 2 2004Isabelle Latour Abstract In humans, three isoforms of the T-type (Cav3.1) calcium-channel ,1 subunit have been reported as a result of alternate splicing of exons 25 and 26 in the III,IV linker region (Cav3.1a, Cav3.1b or Cav3.1bc). In the present study, we report that human glioma express Cav3.1 channels in situ, that splicing of these exons is uniquely regulated and that there is expression of a glioma-specific novel T-type variant (Cav3.1ac). Seven human glioma samples were collected at surgery, RNA was extracted, and cDNA was produced for RT-PCR analysis. In addition, three glioma cell lines (U87, U563, and U251N), primary cultures of human fetal astrocytes, as well as adult and fetal human brain cDNA were used. Previously described Cav3.1 splice variants were present in glioma samples, cultured cells and whole brain. Consistent with the literature, our results reveal that in the normal adult brain, Cav3.1a transcripts predominate, while Cav3.1b is mostly fetal-specific. RT-PCR results on glioma and glioma cell lines showed that Cav3.1 expression in tumor cells resemble fetal brain expression pattern as Cav3.1bc is predominantly expressed. In addition, we identified a novel splice variant, Cav3.1ac, expressed in three glioma biopsies and one glioma cell line, but not in normal brain or fetal astrocytes. Transient expression of this variant demonstrates that Cav3.1ac displays similar current-voltage and steady-state inactivation properties compared with Cav3.1b, but a slower recovery from inactivation. Taken together, our data suggest glioma-specific Cav3.1 gene regulation, which could possibly contribute to tumor pathogenesis. © 2004 Wiley-Liss, Inc. [source] Noninvasive dynamic imaging of seizures in epileptic patientsHUMAN BRAIN MAPPING, Issue 12 2009Louise Tyvaert Abstract Epileptic seizures are due to abnormal synchronized neuronal discharges. Techniques measuring electrical changes are commonly used to analyze seizures. Neuronal activity can be also defined by concomitant hemodynamic and metabolic changes. Simultaneous electroencephalogram (EEG)-functional MRI (fMRI) measures noninvasively with a high-spatial resolution BOLD changes during seizures in the whole brain. Until now, only a static image representing the whole seizure was provided. We report in 10 focal epilepsy patients a new approach to dynamic imaging of seizures including the BOLD time course of seizures and the identification of brain structures involved in seizure onset and discharge propagation. The first activation was observed in agreement with the expected location of the focus based on clinical and EEG data (three intracranial recordings), thus providing validity to this approach. The BOLD signal preceded ictal EEG changes in two cases. EEG-fMRI may detect changes in smaller and deeper structures than scalp EEG, which can only record activity form superficial cortical areas. This method allowed us to demonstrate that seizure onset zone was limited to one structure, thus supporting the concept of epileptic focus, but that a complex neuronal network was involved during propagation. Deactivations were also found during seizures, usually appearing after the first activation in areas close or distant to the activated regions. Deactivations may correspond to actively inhibited regions or to functional disconnection from normally active regions. This new noninvasive approach should open the study of seizure generation and propagation mechanisms in the whole brain to groups of patients with focal epilepsies. Hum Brain Mapp, 2009. © 2009 Wiley-Liss, Inc. [source] Isotropic resolution diffusion tensor imaging with whole brain acquisition in a clinically acceptable timeHUMAN BRAIN MAPPING, Issue 4 2002Derek Kenton Jones Abstract Our objective was to develop a diffusion tensor MR imaging pulse sequence that allows whole brain coverage with isotropic resolution within a clinically acceptable time. A single-shot, cardiac-gated MR pulse sequence, optimized for measuring the diffusion tensor in human brain, was developed to provide whole-brain coverage with isotropic (2.5 × 2.5 × 2.5 mm) spatial resolution, within a total imaging time of approximately 15 min. The diffusion tensor was computed for each voxel in the whole volume and the data processed for visualization in three orthogonal planes. Anisotropy data were further visualized using a maximum-intensity projection algorithm. Finally, reconstruction of fiber-tract trajectories i.e., ,tractography' was performed. Images obtained with this pulse sequence provide clear delineation of individual white matter tracts, from the most superior cortical regions down to the cerebellum and brain stem. Because the data are acquired with isotropic resolution, they can be reformatted in any plane and the sequence can therefore be used, in general, for macroscopic neurological or psychiatric neuroimaging investigations. The 3D visualization afforded by maximum intensity projection imaging and tractography provided easy visualization of individual white matter fasciculi, which may be important sites of neuropathological degeneration or abnormal brain development. This study has shown that it is possible to obtain robust, high quality diffusion tensor MR data at 1.5 Tesla with isotropic resolution (2.5 × 2.5 × 2.5 mm) from the whole brain within a sufficiently short imaging time that it may be incorporated into clinical imaging protocols. Hum. Brain Mapping 15:216,230, 2002. © 2002 Wiley-Liss, Inc. [source] Toward a practical protocol for human optic nerve DTI with EPI geometric distortion correctionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2009Udomchai Techavipoo PhD Abstract Purpose To develop a practical protocol for diffusion tensor imaging (DTI) of the human optic nerve with echo planar imaging (EPI) geometric distortion correction. Materials and Methods A conventional DTI protocol was modified to acquire images with fat and cerebrospinal fluid (CSF) suppression and field inhomogeneity maps of contiguous coronal slices covering the whole brain. The technique was applied to healthy volunteers and multiple sclerosis patients with and without a history of unilateral optic neuritis. DTI measures and optic nerve tractography before and after geometric distortion correction were compared. Diffusion measures from left and right or from affected and unaffected eyes in different subject cohorts were reported. Results The image geometry after correction closely resembled reference anatomical images. Optic nerve tractography became feasible after distortion correction. The diffusion measures from the healthy volunteers were in good agreement with the literature. Statistically significant differences were found in the fractional anisotropy and orthogonal eigenvalues between affected and unaffected eyes in optic neuritis patients with poor recovery. The diffusion measures before and after geometric distortion correction were not significantly different. For cohorts without optic neuritis, the difference between diffusion measures from left and right eyes was not statistically significant. Conclusion The proposed technique could provide a practical DTI protocol to study the human optic nerve. J. Magn. Reson. Imaging 2009;30:699,707. © 2009 Wiley-Liss, Inc. [source] 3D diffusion tensor MRI with isotropic resolution using a steady-state radial acquisitionJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2009Youngkyoo Jung PhD Abstract Purpose To obtain diffusion tensor images (DTI) over a large image volume rapidly with 3D isotropic spatial resolution, minimal spatial distortions, and reduced motion artifacts, a diffusion-weighted steady-state 3D projection (SS 3DPR) pulse sequence was developed. Materials and Methods A diffusion gradient was inserted in a SS 3DPR pulse sequence. The acquisition was synchronized to the cardiac cycle, linear phase errors were corrected along the readout direction, and each projection was weighted by measures of consistency with other data. A new iterative parallel imaging reconstruction method was also implemented for removing off-resonance and undersampling artifacts simultaneously. Results The contrast and appearance of both the fractional anisotropy and eigenvector color maps were substantially improved after all correction techniques were applied. True 3D DTI datasets were obtained in vivo over the whole brain (240 mm field of view in all directions) with 1.87 mm isotropic spatial resolution, six diffusion encoding directions in under 19 minutes. Conclusion A true 3D DTI pulse sequence with high isotropic spatial resolution was developed for whole brain imaging in under 20 minutes. To minimize the effects of brain motion, a cardiac synchronized, multiecho, DW-SSFP pulse sequence was implemented. Motion artifacts were further reduced by a combination of linear phase correction, corrupt projection detection and rejection, sampling density reweighting, and parallel imaging reconstruction. The combination of these methods greatly improved the quality of 3D DTI in the brain. J. Magn. Reson. Imaging 2009;29:1175,1184. © 2009 Wiley-Liss, Inc. [source] Quantitative analysis of MRI signal abnormalities of brain white matter with high reproducibility and accuracyJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 2 2002Xingchang Wei MD Abstract Purpose To assess the reproducibility and accuracy compared to radiologists of three automated segmentation pipelines for quantitative magnetic resonance imaging (MRI) measurement of brain white matter signal abnormalities (WMSA). Materials and Methods WMSA segmentation was performed on pairs of whole brain scans from 20 patients with multiple sclerosis (MS) and 10 older subjects who were positioned and imaged twice within 30 minutes. Radiologist outlines of WMSA on 20 sections from 16 patients were compared with the corresponding results of each segmentation method. Results The segmentation method combining expectation-maximization (EM) tissue segmentation, template-driven segmentation (TDS), and partial volume effect correction (PVEC) demonstrated the highest accuracy (the absolute value of the Z-score was 0.99 for both groups of subjects), as well as high interscan reproducibility (repeatability coefficient was 0.68 mL in MS patients and 1.49 mL in aging subjects). Conclusion The addition of TDS to the EM segmentation and PVEC algorithms significantly improved the accuracy of WMSA volume measurements, while also improving measurement reproducibility. J. Magn. Reson. Imaging 2002;15:203,209. © 2002 Wiley-Liss, Inc. [source] Proteomic analysis of nuclear factors binding to an intronic enhancer in the myelin proteolipid protein geneJOURNAL OF NEUROCHEMISTRY, Issue 5 2008Anna Dobretsova Abstract The myelin proteolipid protein gene (Plp1) encodes the most abundant protein found in CNS myelin, accounting for nearly one-half of the total protein. Its expression in oligodendrocytes is developmentally regulated , peaking during the active myelination period of CNS development. Previously, we have identified a novel enhancer (designated ASE) in intron 1 DNA that appears to be important in mediating the surge of Plp1 gene activity during the active myelination period. Evidence suggests that the ASE participates in the formation of a specialized multi-protein/DNA complex called an enhanceosome. The current study describes an optimized, five-step, DNA affinity chromatography purification procedure to purify nuclear proteins from mouse brain that bind to the 85-bp ASE sequence, specifically. Electrophoretic mobility shift assay analysis demonstrated that specific DNA-binding activity was retained throughout the purification procedure, resulting in concomitant enrichment of nucleoprotein complexes. Identification of the purported regulatory factors was achieved through mass spectrometry analysis and included over 20 sequence-specific DNA-binding proteins. Supplementary western blot analyses to determine which of these sequence-specific factors are present in oligodendrocytes, and their developmental and regional expression in whole brain, suggest that Pur, and Pur, rank highest among the candidate factors as constituents of the multi-protein complex formed on the ASE. [source] A Magnetization Transfer MRI Study of Deep Gray Matter Involvement in Multiple SclerosisJOURNAL OF NEUROIMAGING, Issue 4 2006Jitendra Sharma MD ABSTRACT Background/Purpose: Gray matter involvement in multiple sclerosis (MS) is of growing interest with respect to disease pathogenesis. Magnetization transfer imaging (MTI), an advanced MRI technique, is sensitive to disease in normal appearing white matter (NAWM) in patients with MS. Design/Methods: We tested if MTI detected subcortical (deep) gray matter abnormalities in patients with MS (n= 60) vs. age-matched normal controls (NL, n= 20). Magnetization transfer ratio (MTR) maps were produced from axial proton density, conventional spin-echo, 5 mm gapless slices covering the whole brain. Region-of-interest,derived MTR histograms for the caudate, putamen, globus pallidus, thalamus, and NAWM were obtained. Whole brain MTR was also measured. Results: Mean whole brain MTR and the peak position of the NAWM MTR histogram were lower in patients with MS than NL (P < .001) and mean whole brain MTR was lower in secondary progressive (SP, n= 10) than relapsing-remitting (RR, n= 50, P < .001) patients. However, none of the subcortical gray matter nuclei showed MTR differences in MS vs. NL, RR vs. SP, or SP vs. NL. Conclusions: The MTI technique used in this cohort was relatively insensitive to disease in the deep gray matter nuclei despite showing sensitivity for whole brain disease in MS. It remains to be determined if other MRI techniques are more sensitive than MTI for detecting pathology in these areas. [source] Moonlight affects nocturnal Period2 transcript levels in the pineal gland of the reef fish Siganus guttatusJOURNAL OF PINEAL RESEARCH, Issue 2 2008Nozomi Sugama Abstract:, The golden rabbitfish Siganus guttatus is a reef fish with a restricted lunar-synchronized spawning cycle. It is not known how the fish recognizes cues from the moon and exerts moon-related activities. In order to evaluate the perception and utilization of moonlight by the fish, the present study aimed to clone and characterize Period2 (Per2), a light-inducible clock gene in lower vertebrates, and to examine daily variations in rabbitfish Per2 (rfPer2) expression as well as the effect of light and moonlight on its expression in the pineal gland. The partially-cloned rfPer2 cDNA (2933 bp) was highly homologous (72%) to zebrafish Per2. The rfPer2 levels increased at ZT6 and decreased at ZT18 in the whole brain and several peripheral organs. The rfPer2 expression in the pineal gland exhibited a daily variation with an increase during daytime. Exposing the fish to light during nighttime resulted in a rapid increase of its expression in the pineal gland, while the level was decreased by intercepting light during daytime. Two hours after exposing the fish to moonlight at the full moon period, the rfPer2 expression was upregulated. These results suggest that rfPer2 is a light-inducible clock gene and that its expression is affected not only by daylight but also by moonlight. Since the rfPer2 expression level during the full moon period was higher than that during the new moon period, the monthly variation in the rfPer2 expression is likely to occur with the change in amplitude between the full and new moon periods. [source] High-resolution magnetic resonance angiography in the mouse using a nanoparticle blood-pool contrast agentMAGNETIC RESONANCE IN MEDICINE, Issue 6 2009Gabriel P. Howles Abstract High-resolution magnetic resonance angiography is already a useful tool for studying mouse models of human disease. Magnetic resonance angiography in the mouse is typically performed using time-of-flight contrast. In this work, a new long-circulating blood-pool contrast agent,a liposomal nanoparticle with surface-conjugated gadolinium (SC-Gd liposomes),was evaluated for use in mouse neurovascular magnetic resonance angiography. A total of 12 mice were imaged. Scan parameters were optimized for both time-of-flight and SC-Gd contrast. Compared to time-of-flight contrast, SC-Gd liposomes (0.08 mmol/kg) enabled improved small-vessel contrast-to-noise ratio, larger field of view, shorter scan time, and imaging of venous structures. For a limited field of view, time-of-flight and SC-Gd were not significantly different; however, SC-Gd provided better contrast-to-noise ratio when the field of view encompassed the whole brain (P < 0.001) or the whole neurovascular axis (P < 0.001). SC-Gd allowed acquisition of high-resolution magnetic resonance angiography (52 × 52 × 100 micrometer3 or 0.27 nL), with 123% higher (P < 0.001) contrast-to-noise ratio in comparable scan time (,45 min). Alternatively, SC-Gd liposomes could be used to acquire high-resolution magnetic resonance angiography (0.27 nL) with 32% higher contrast-to-noise ratio (P < 0.001) in 75% shorter scan time (12 min). Magn Reson Med, 2009. © 2009 Wiley-Liss, Inc. [source] Evidence for enhanced functional activity of cervical cord in relapsing multiple sclerosisMAGNETIC RESONANCE IN MEDICINE, Issue 5 2008F. Agosta Abstract Functional MRI (fMRI) was used to assess proprioceptive-associated cervical cord activity in 24 relapsing multiple sclerosis (MS) patients and 10 controls. Cord and brain conventional and diffusion tensor (DT) MRI were also acquired. fMRI was performed using a block design during a proprioceptive stimulation consisting of a passive flexion-extension of the right upper limb. Cord lesion number, cross-sectional area, mean diffusivity (MD) and fractional anisotropy (FA), whole brain and left corticospinal tract lesion volume (LV), gray matter (GM) MD, and normal-appearing white matter (NAWM) MD and FA were calculated. MS patients had higher average cord fMRI signal changes than controls (3.4% vs. 2.7%, P = 0.03). Compared to controls, MS patients also had a higher average signal change in the anterior section of the right cord at C5 (P = 0.005) and left cord at C5,C6 (P = 0.03), whereas no difference was found in the other cord sections. Cord average signal change correlated significantly with cord FA and brain left corticospinal tract LV, GM-MD, and NAWM-FA. This study shows an abnormal pattern of activations in the cervical cord of MS patients following proprioceptive stimulation. Cord fMRI changes might have a role in limiting the clinical consequences of MS associated with irreversible tissue damage. Magn Reson Med 59:1035,1042, 2008. © 2008 Wiley-Liss, Inc. [source] Quantitative magnetization transfer mapping of bound protons in multiple sclerosisMAGNETIC RESONANCE IN MEDICINE, Issue 1 2003D. Tozer Abstract Quantitative analysis of magnetization transfer images has the potential to allow a more thorough characterization of the protons, both bound and free, in a tissue by extracting a number of parameters relating to the NMR properties of the protons and their local environment. This work develops previously presented techniques to produce estimates of parameters such as the bound proton fraction, f, and the transverse relaxation time of the bound pool, T2B, for the whole brain in a clinically acceptable imaging time. This is achieved by limiting the number of data collected (typically to 10); to collect 28 5-mm slices with a reconstructed resolution of 0.94 × 0.94 mm. The protocol takes 82 sec per data point. The fitting technique is assessed against previous work and for fitting failures. Maps and analysis are presented from a group of seven controls and 20 multiple sclerosis patients. The maps show that the parameters are sensitive to tissue-specific differences and can detect pathological change within lesions. Statistically significant differences in parameters such as T2B and f are seen between normal-appearing white matter, multiple sclerosis lesions, and control white matter. Whole-brain histograms of these parameters are also presented, showing differences between patients and controls. Magn Reson Med 50:83,91, 2003. © 2003 Wiley-Liss, Inc. [source] Pick's disease with Pick bodies combined with progressive supranuclear palsy without tuft-shaped astrocytes: A clinical, neuroradiologic and pathological study of an autopsied caseNEUROPATHOLOGY, Issue 3 2006Lu-Ning Wang We report clinical, neuroradiologic features, and neuropathologic findings of a 76-year-old man with coexistent Pick's disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed-ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau- and ubiquitin-positive in neurons of layers II,III of the above-mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau-positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned-astrocytes and coiled bodies but no-tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick's disease and coexistence with progressive supranuclear palsy without tuft-shaped astrocytes. [source] Reflections on the application of 13C-MRS to research on brain metabolismNMR IN BIOMEDICINE, Issue 6-7 2003Peter Morris Abstract The power of 13C-MRS lies in its unique chemical specificity, enabling detection and quantification of metabolic intermediates which would not be so readily monitored using conventional radiochemical techniques. Examples from animal studies, by examination of tissue extracts from the whole brain, brain slices and cultured cells, include observation of intermediates such as citrate and triose phosphates which have yielded novel information on neuronal/glial relationships. The use of 13C-labelled acetate as a specific precursor for glial metabolism provided evidence in support of the view that some of the GABA produced in the brain is derived from glial glutamine. Such studies have also provided direct evidence on the contribution of anaplerotic pathways to intermediary metabolism. Analogous studies are now being performed on the human brain, where 13C-acetate is used to quantitate the overall contribution of glial cells to intermediary metabolism, and use of 13C-glucose enables direct calculation of rates of flux through the TCA (FTCA) and of the glutamate,glutamine cycle (FCYC), leading to the conclusion that the rate of glial recycling of glutamate accounts for some 50% of FTCA. The rate of 0.74,,mol,min,1,g,1 for FTCA is compatible with PET rates of CMRglc of 0.3,0.4,,mol,min,1,g,1 (since each glucose molecule yields two molecules of pyruvate entering the TCA). Our brain activation studies showed a 60% increase in FTCA, which is very similar to the increases in CBF and in CMRglc observed in PET activation studies. Copyright © 2003 John Wiley & Sons, Ltd. [source] Isatin-binding proteins of rat and mouse brain: Proteomic identification and optical biosensor validationPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 1 2010Olga Buneeva Abstract Isatin (indole-2,3-dione) is an endogenous indole that has a distinct and discontinuous distribution in the brain and in other mammalian tissues and body fluids. Its output is increased under conditions of stress and anxiety. Isatin itself and its analogues exhibit a wide range of pharmacological activities but its specific biological targets still are not well characterized. Affinity chromatography of Triton X-100 lysates of soluble and particulate fractions of mouse and rat whole brain homogenates on 5-aminocaproyl-isatin-Sepharose followed by subsequent proteomic analysis resulted in identification of 65 and 64 individual proteins, respectively. Isatin-binding capacity of some of the identified proteins has been validated in an optical biosensor study using a Biacore 3000 optical biosensor, 5-aminocarproyl-isatin, and 5-aminoisatin as the affinity ligands. The Kd values (of 0.1,20,,M) obtained during the optical biosensor experiments were consistent with the range of Kd values recently reported for [3H]isatin binding to brain sections. Although the number of isatin-binding proteins identified in the mouse and rat brain was similar, only 21 proteins (about one-third) were identical in the two species. This may be one reason for the differences in isatin effects in rats and mice reported in the literature. [source] Matrix-assisted laser desorption/ionization imaging mass spectrometry for direct measurement of clozapine in rat brain tissueRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 6 2006Yunsheng Hsieh Matrix-assisted laser desorption/ionization hyphenated with quadrupole time-of-flight (QTOF) mass spectrometry (MS) has been used to directly determine the distribution of pharmaceuticals in rat brain tissue slices which might unravel their disposition for new drug development. Clozapine, an antipsychotic drug, and norclozapine were used as model compounds to investigate fundamental parameters such as matrix and solvent effects and irradiance dependence on MALDI intensity but also to address the issues with direct tissue imaging MS technique such as (1) uniform coating by the matrix, (2) linearity of MALDI signals, and (3) redistribution of surface analytes. The tissue sections were coated with various matrices on MALDI plates by airspray deposition prior to MS detection. MALDI signals of analytes were detected by monitoring the dissociation of the individual protonated molecules to their predominant MS/MS product ions. The matrices were chosen for tissue applications based on their ability to form a homogeneous coating of dense crystals and to yield greater sensitivity. Images revealing the spatial localization in tissue sections using MALDI-QTOF following a direct infusion of 3H-clozapine into rat brain were found to be in good correlation with those using a radioautographic approach. The density of clozapine and its major metabolites from whole brain homogenates was further confirmed using fast high-performance liquid chromatography/tandem mass spectrometry (HPLC-MS/MS) procedures. Copyright © 2006 John Wiley & Sons, Ltd. [source] Brain of the African elephant (Loxodonta africana): Neuroanatomy from magnetic resonance imagesTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 1 2005Atiya Y. Hakeem Abstract We acquired magnetic resonance images of the brain of an adult African elephant, Loxodonta africana, in the axial and parasagittal planes and produced anatomically labeled images. We quantified the volume of the whole brain (3,886.7 cm3) and of the neocortical and cerebellar gray and white matter. The white matter-to-gray matter ratio in the elephant neocortex and cerebellum is in keeping with that expected for a brain of this size. The ratio of neocortical gray matter volume to corpus callosum cross-sectional area is similar in the elephant and human brains (108 and 93.7, respectively), emphasizing the difference between terrestrial mammals and cetaceans, which have a very small corpus callosum relative to the volume of neocortical gray matter (ratio of 181,287 in our sample). Finally, the elephant has an unusually large and convoluted hippocampus compared to primates and especially to cetaceans. This may be related to the extremely long social and chemical memory of elephants. © 2005 Wiley-Liss, Inc. [source] Volumetric and lateralized differences in selected brain regions of chimpanzees (Pan troglodytes) and bonobos (Pan paniscus)AMERICAN JOURNAL OF PRIMATOLOGY, Issue 12 2009William D. Hopkins Abstract The two species of Pan, bonobos and common chimpanzees, have been reported to have different social organization, cognitive and linguistic abilities and motor skill, despite their close biological relationship. Here, we examined whether bonobos and chimpanzee differ in selected brain regions that may map to these different social and cognitive abilities. Eight chimpanzees and eight bonobos matched on age, sex and rearing experiences were magnetic resonance images scanned and volumetric measures were obtained for the whole brain, cerebellum, striatum, motor-hand area, hippocampus, inferior frontal gyrus and planum temporale. Chimpanzees had significantly larger cerebellum and borderline significantly larger hippocampus and putamen, after adjusting for brain size, compared with bonobos. Bonobos showed greater leftward asymmetries in the striatum and motor-hand area compared with chimpanzees. No significant differences in either the volume or lateralization for the so-called language homologs were found between species. The results suggest that the two species of Pan are quite similar neurologically, though some volumetric and lateralized differences may reflect inherent differences in social organization, cognition and motor skills. Am. J. Primatol. 71:988,997, 2009. © 2009 Wiley-Liss, Inc. [source] The Brain of the Dog in Section: a Comprehensive View for Veterinary StudentsANATOMIA, HISTOLOGIA, EMBRYOLOGIA, Issue 2005I. Salazar Transversal, horizontal and sagittal sections of the brain were stained by the ancient but efficient Mulligan method, a procedure that establishes a clear macroscopic difference between the white and grey substances. Different structures of each section were studied and most of the details were identified and named according to the NAV. All sections were projected onto the whole brain. By means of this easy and basic procedure the students increase their understanding of (1) the size and/or the form and/or the topography of several prominent structures of the brain, (2) the general distribution of the substancia alba and grisea, and they begin to understand the complexity of the brain. [source] Four Weeks' Inhalation Exposure of Long Evans Rats to 4- tert -Butyltoluene: Effect on Evoked Potentials, Behaviour, and Brain NeurochemistryBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 1 2000Henrik Rye Lam Long-lasting central nervous system (CNS) neurotoxicity of 4- tert -butyltoluene (TBT) has been investigated using electrophysiology, behaviour, and neurochemistry in Long Evans rats exposed by inhalation to 0, 20, or 40 p.p.m. TBT 6 hr/day, 7 days/week for 4 weeks. Flash evoked potentials and somatosensory evoked potentials were not affected by TBT. In Auditory Brain Stem Response there was no shift in hearing threshold, but the amplitude of the first wave was increased in both exposed groups at high stimulus levels. Three to four months after the end of exposure, behavioural studies in Morris water maze and eight-arm maze failed to demonstrate any TBT induced effects. Exposure was followed by a 5 months exposure-free period prior to gross regional and subcellular (synaptosomal) neurochemical investigations of the brain. TBT reduced the NA concentration in whole brain minus cerebellum. Synaptosomal choline acetyltransferase activity increased and acetylcholinesterase activity was unchanged suggesting increased synaptosomal ability for acetylcholine synthesis. The relative and total yield of synaptosomal protein was reduced suggesting reduced density and total number of synapses in situ, respectively. We hypothesise that a reduced yield of synaptosomal protein reflects a more general effect of organic solvent exposure on the software of the brain. The synaptosomal concentration per mg synaptosomal protein and the total amount of 5-hydroxytryptamine were not affected whereas the total amount of synaptosomal noradrenaline decreased. The concentration and the total amount of synaptosomal dopamine decreased. The noradrenergic and dopaminergic parts of CNS may be more vulnerable to TBT than the serotonergic, and these long-lasting effects may cause or reflect TBT-compromised CNS function. [source] MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 7 2009Meizhen Chen Abstract Neurogenesis during development depends on the coordinated regulation of self-renewal and differentiation of neural precursor cells (NPCs). Chromatin regulation is a key step in self-renewal activity and fate decision of NPCs. However, the molecular mechanism or mechanisms of this regulation is not fully understood. Here, we demonstrate for the first time that MRG15, a chromatin regulator, is important for proliferation and neural fate decision of NPCs. Neuroepithelia from Mrg15 -deficient embryonic brain are much thinner than those from control, and apoptotic cells increase in this region. We isolated NPCs from Mrg15 -deficient and wild-type embryonic whole brains and produced neurospheres to measure the self-renewal and differentiation abilities of these cells in vitro. Neurospheres culture from Mrg15 -deficient embryo grew less efficiently than those from wild type. Measurement of proliferation by means of BrdU (bromodeoxyuridine) incorporation revealed that Mrg15 -deficient NPCs have reduced proliferation ability and apoptotic cells do not increase during in vitro culture. The reduced proliferation of Mrg15 -deficient NPCs most likely accounts for the thinner neuroepithelia in Mrg15 -deficient embryonic brain. Moreover, we also demonstrate Mrg15 -deficient NPCs are defective in differentiation into neurons in vitro. Our results demonstrate that MRG15 has more than one function in neurogenesis and defines a novel role for this chromatin regulator that integrates proliferation and cell-fate determination in neurogenesis during development. © 2008 Wiley-Liss, Inc. [source] Catecholamine synthesis and metabolism in the central nervous system of mice lacking ,2 -adrenoceptor subtypesBRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2009MA Vieira-Coelho Background and purpose:, This study investigates the role of ,2 -adrenoceptor subtypes, ,2A, ,2B and ,2C, on catecholamine synthesis and catabolism in the central nervous system of mice. Experimental approach:, Activities of the main catecholamine synthetic and catabolic enzymes were determined in whole brains obtained from ,2A -, ,2B - and ,2C -adrenoceptor knockout (KO) and C56Bl\7 wild-type (WT) mice. Key results:, Although no significant differences were found in tyrosine hydroxylase activity and expression, brain tissue levels of 3,4-dihydroxyphenylalanine were threefold higher in ,2A - and ,2C -adrenoceptor KO mice. Brain tissue levels of dopamine and noradrenaline were significantly higher in ,2A and ,2CKOs compared with WT [WT: 2.8 ± 0.5, 1.1 ± 0.1; ,2AKO: 6.9 ± 0.7, 1.9 ± 0.1; ,2BKO: 2.3 ± 0.2, 1.0 ± 0.1; ,2CKO: 4.6 ± 0.8, 1.5 ± 0.2 nmol·(g tissue),1, for dopamine and noradrenaline respectively]. Aromatic L-amino acid decarboxylase activity was significantly higher in ,2A and ,2CKO [WT: 40 ± 1; ,2A: 77 ± 2; ,2B: 40 ± 1; ,2C: 50 ± 1, maximum velocity (Vmax) in nmol·(mg protein),1·h,1], but no significant differences were found in dopamine ,-hydroxylase. Of the catabolic enzymes, catechol- O -methyltransferase enzyme activity was significantly higher in all three ,2KO mice [WT: 2.0 ± 0.0; ,2A: 2.4 ± 0.1; ,2B: 2.2 ± 0.0; ,2C: 2.2 ± 0.0 nmol·(mg protein),1·h,1], but no significant differences were found in monoamine oxidase activity between all ,2KOs and WT mice. Conclusions and implications:, In mouse brain, deletion of ,2A - or ,2C -adrenoceptors increased cerebral aromatic L-amino acid decarboxylase activity and catecholamine tissue levels. Deletion of any ,2 -adrenoceptor subtypes resulted in increased activity of catechol- O -methyltransferase. Higher 3,4-dihydroxyphenylalanine tissue levels in ,2A and ,2CKO mice could be explained by increased 3,4-dihydroxyphenylalanine transport. [source] |