http://www.biomedcentral.com/bmcneurosci/ The latest research articles published by BMC Neuroscience 2009-07-08T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ Background: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion mutation in the coding region of a novel gene. The mechanism of HD is unknown. Most data suggest that polyglutamine-mediated aggregation associated with expression of mutant huntingtin protein (mhtt) contributes to the pathology. However, recent studies have identified early cellular dysfunctions that preclude aggregate formation. Suppression of aggregation is accepted as one of the markers of successful therapeutic approaches. Previously, we demonstrated that tricyclic pyrone (TP) compounds efficiently inhibited formation of amyloid-beta (Abeta) aggregates in cell and mouse models representing Alzheimer's Disease (AD). In the present study, we aimed to determine whether TP compounds could prevent aggregation and restore early cellular defects in primary embryonic striatal neurons from animal model representing HD. Results: TP compounds effectively inhibit aggregation caused by mhtt in neurons and glial cells. Treatment with TP compounds also alleviated cholesterol accumulation and restored clathrin-independent endocytosis in HD neurons. Conclusions: We have found that TP compounds not only blocked mhtt-induced aggregation, but also alleviated early cellular dysfunctions that preclude aggregate formation. Our data suggest TP molecules may be used as lead compounds for prevention or treatment of multiple neurodegenerative diseases including HD and AD. http://www.biomedcentral.com/1471-2202/10/73 Eugenia Trushina Sandeep Rana Cynthia McMurray Duy Hua BMC Neuroscience 2009, 10:73 2009-07-08T00:00:00Z doi:10.1186/1471-2202-10-73 BMC Neuroscience 1471-2202 10 73 2009-07-08T00:00:00Z PDF Background: Following practice of skilled movements, changes continue to take place in the brain that both strengthen and modify memory for motor learning. These changes represent motor memory consolidation a process whereby new memories are transformed from a fragile to a more permanent, robust and stable state. In the present study, the neural correlates of motor memory consolidation were probed using repetitive transcranial magnetic stimulation (rTMS) to the dorsal premotor cortex (PMd). Participants engaged in four days of continuous tracking practice that immediately followed either excitatory 5 HZ, inhibitory 1 HZ or control, sham rTMS. A delayed retention test assessed motor learning of repeated and random sequences of continuous movement; no rTMS was applied at retention. Results: We discovered that 5 HZ excitatory rTMS to PMd stimulated motor memory consolidation as evidenced by off-line learning, whereas only memory stabilization was noted following 1 Hz inhibitory or sham stimulation. Conclusions: Our data support the hypothesis that PMd is important for continuous motor learning, specifically via off-line consolidation of learned motor behaviors. http://www.biomedcentral.com/1471-2202/10/72 Lara Boyd Meghan Linsdell BMC Neuroscience 2009, 10:72 2009-07-07T00:00:00Z doi:10.1186/1471-2202-10-72 BMC Neuroscience 1471-2202 10 72 2009-07-07T00:00:00Z PDF Background: Dysphagia is a leading complication in stroke patients causing aspiration pneumonia, malnutrition and increased mortality. Current strategies of swallowing therapy involve on the one hand modification of eating behaviour or swallowing technique and on the other hand facilitation of swallowing with the use of pharyngeal sensory stimulation. Thermal tactile oral stimulation (TTOS) is an established method to treat patients with neurogenic dysphagia especially if caused by sensory deficits. Little is known about the possible mechanisms by which this interventional therapy may work. We employed whole-head MEG to study changes in cortical activation during self-paced volitional swallowing in fifteen healthy subjects with and without TTOS. Data were analyzed by means of synthetic aperture magnetometry (SAM) and the group analysis of individual SAM data was performed using a permutation test. Results: Compared to the normal swallowing task a significantly increased bilateral cortical activation was seen after oropharyngeal stimulation. Analysis of the chronological changes during swallowing suggests facilitation of both the oral and the pharyngeal phase of deglutition. Conclusions: In the present study functional cortical changes elicited by oral sensory stimulation could be demonstrated. We suggest that these results reflect short-term cortical plasticity of sensory swallowing areas. These findings facilitate our understanding of the role of cortical reorganization in dysphagia treatment and recovery. http://www.biomedcentral.com/1471-2202/10/71 Inga Teismann Olaf Steinstraeter Tobias Warnecke Sonja Suntrup Erich Ringelstein Christo Pantev Rainer Dziewas BMC Neuroscience 2009, 10:71 2009-06-30T00:00:00Z doi:10.1186/1471-2202-10-71 BMC Neuroscience 1471-2202 10 71 2009-06-30T00:00:00Z PDF Background: Histamine-related drugs are commonly used in the treatment of vertigo and related vestibular disorders. The site of action of these drugs however has not been elucidated yet. Recent works on amphibians showed that histamine H3 receptor antagonists, e.g. betahistine, inhibit the afferent discharge recorded from the vestibular nerve. To assess the expression of H3 histamine receptors in vestibular neurons, we performed mRNA RT-PCR and immunofluorescence experiments in mouse Scarpa's ganglia. Results: RT-PCR analysis showed the presence of H3 receptor mRNA in mouse ganglia tissue. H3 protein expression was found in vestibular neurons characterized by large and roundish soma, which labeled for calretinin and calbindin. Conclusions: The present results are consistent with calyx and dimorphic, but not bouton, afferent vestibular neurons expressing H3 receptors. This study provides a molecular substrate for the effects of histamine-related antivertigo drugs acting on (or binding to) H3 receptors, and suggest a potential target for the treatment of vestibular disorders of peripheral origin. http://www.biomedcentral.com/1471-2202/10/70 Simona Tritto Laura Botta Valeria Zampini Gianpiero Zucca Paolo Valli Sergio Masetto BMC Neuroscience 2009, 10:70 2009-06-29T00:00:00Z doi:10.1186/1471-2202-10-70 BMC Neuroscience 1471-2202 10 70 2009-06-29T00:00:00Z PDF Background: Several event related potential (ERP) studies have investigated the time course of different aspects of evaluative processing in social bias research. Various reports suggest that the late positive potential (LPP) is modulated by basic evaluative processes, and some reports suggest that in-/outgroup relative position affects ERP responses. In order to study possible LPP blending between facial race processing and semantic valence (positive or negative words), we recorded ERPs while indigenous and non-indigenous participants who were matched by age and gender performed an implicit association test (IAT). The task involved categorizing faces (ingroup and outgroup) and words (positive and negative). Since our paradigm implies an evaluative task with positive and negative valence association, a frontal distribution of LPPs similar to that found in previous reports was expected. At the same time, we predicted that LPP valence lateralization would be modulated not only by positive/negative associations but also by particular combinations of valence, face stimuli and participant relative position. Results: Results showed that, during an IAT, indigenous participants with greater behavioral ingroup bias displayed a frontal LPP that was modulated in terms of complex contextual associations involving ethnic group and valence. The LPP was lateralized to the right for negative valence stimuli and to the left for positive valence stimuli. This valence lateralization was influenced by the combination of valence and membership type relevant to compatibility with prejudice toward a minority. Behavioral data from the IAT and an explicit attitudes questionnaire were used to clarify this finding and showed that ingroup bias plays an important role. Both ingroup favoritism and indigenous/non-indigenous differences were consistently present in the data. Conclusions: Our results suggest that frontal LPP is elicited by contextual blending of evaluative judgments of in-/outgroup information and positive vs. negative valence association and confirm recent research relating in-/outgroup ERP modulation and frontal LPP. LPP modulation may cohere with implicit measures of attitudes. The convergence of measures that were observed supports the idea that racial and valence evaluations are strongly influenced by context. This result adds to a growing set of evidence concerning contextual sensitivity of different measures of prejudice. http://www.biomedcentral.com/1471-2202/10/69 Esteban Hurtado Andres Haye Ramiro Gonzalez Facundo Manes Agustin Ibanez BMC Neuroscience 2009, 10:69 2009-06-26T00:00:00Z doi:10.1186/1471-2202-10-69 BMC Neuroscience 1471-2202 10 69 2009-06-26T00:00:00Z PDF Background: Brain-derived neurotrophic factor (BDNF) is a small secreted protein that has important roles in the developing and adult nervous system. Altered expression or changes in the regulation of the BDNF gene have been implicated in a variety of human nervous system disorders. Although regulation of the rodent BDNF gene has been extensively investigated, in vivo studies regarding the human BDNF gene are largely limited to postmortem analysis. Bacterial artificial chromosome (BAC) transgenic mice harboring the human BDNF gene and its regulatory flanking sequences constitute a useful tool for studying human BDNF gene regulation and for identification of therapeutic compounds modulating BDNF expression. Results: In this study we have generated and analyzed BAC transgenic mice carrying 168 kb of the human BDNF locus modified such that BDNF coding sequence was replaced with the sequence of a fusion protein consisting of N-terminal BDNF and the enhanced green fluorescent protein (EGFP). The human BDNF-BAC construct containing all BDNF 5' exons preceded by different promoters recapitulated the expression of endogenous BDNF mRNA in the brain and several non-neural tissues of transgenic mice. All different 5' exon-specific BDNF-EGFP alternative transcripts were expressed from the transgenic human BDNF-BAC construct, resembling the expression of endogenous BDNF. Furthermore, BDNF-EGFP mRNA was induced upon treatment with kainic acid in a promotor-specific manner, similarly to that of the endogenous mouse BDNF mRNA. Conclusion: Genomic region covering 67 kb of human BDNF gene, 84 kb of upstream and 17 kb of downstream sequences is sufficient to drive tissue-specific and kainic acid-induced expression of the reporter gene in transgenic mice. The pattern of expression of the transgene is highly similar to BDNF gene expression in mouse and human. This is the first study to show that human BDNF gene is regulated by neural activity. http://www.biomedcentral.com/1471-2202/10/68 Indrek Koppel Tamara Aid-Pavlidis Kaur Jaanson Mari Sepp Priit Pruunsild Kaia Palm Tonis Timmusk BMC Neuroscience 2009, 10:68 2009-06-25T00:00:00Z doi:10.1186/1471-2202-10-68 BMC Neuroscience 1471-2202 10 68 2009-06-25T00:00:00Z XML Background: Developmental dyslexia is a specific cognitive disorder in reading acquisition that has genetic and neurological origins. Despite histological evidence for brain differences in dyslexia, we recently demonstrated that in large cohort of subjects, no differences between control and dyslexic readers can be found at the macroscopic level (MRI voxel), because of large variance in brain local volumes. In the present study, we aimed at finding brain areas that most discriminate dyslexic from control normal readers despite the large variance across subjects. After segmenting brain grey matter, normalizing brain size and shape and modulating the voxels' content, normal readers' brains were used to build a 'standard' brain via bootstrapped confidence intervals. Each dyslexic reader's brain was then classified independently at each voxel as being within or outside the normal range. We used this simple strategy to build a brain map showing regional percentages of differences between groups. The significance of this map was then assessed using a randomization technique. Results: The right cerebellar declive and the right lentiform nucleus were the two areas that significantly differed the most between groups with 100% of the dyslexic subjects (N=38) falling outside of the control group (N=39) 95% confidence interval boundaries. The clinical relevance of this result was assessed by inquiring cognitive brain-based differences among dyslexic brain subgroups in comparison to normal readers' performances. The strongest difference between dyslexic subjects was observed between subjects with lower cerebellar declive (LCD) grey matter volumes than controls and subjects with higher cerebellar declive (HCD) grey matter volumes than controls. Dyslexic subjects with LCD volumes performed worse than subjects with HCD volumes in phonologically and lexicon related tasks. Furthermore, cerebellar and lentiform grey matter volumes interacted in dyslexic subjects, so that lower and higher lentiform grey matter volumes compared to controls differently modulated the phonological and lexical performances. Best performances (observed in controls) corresponded to an optimal value of grey matter and they dropped for higher or lower volumes. Conclusion: These results provide evidence for the existence of various subtypes of dyslexia characterized by different brain phenotypes. In addition, behavioural analyses suggest that these brain phenotypes relate to different deficits of automatization of language-based processes such as grapheme/phoneme correspondence or rapid access to lexicon entries. http://www.biomedcentral.com/1471-2202/10/67 Cyril Pernet Jean Baptiste Poline Jean Francois Demonet Guillaume Rousselet BMC Neuroscience 2009, 10:67 2009-06-25T00:00:00Z doi:10.1186/1471-2202-10-67 BMC Neuroscience 1471-2202 10 67 2009-06-25T00:00:00Z PDF Background: Drosophila larval locomotion consists of forward peristalsis interrupted by episodes of pausing, turning and exploratory behavior (head swinging). This behavior can be regulated by visual input as seen by light-induced increase in pausing, head swinging and direction change as well as reduction of linear speed that characterizes the larval photophobic response. During 3rd instar stage, Drosophila larvae gradually cease to be repelled by light and are photoneutral by the time they wander in search for a place to undergo metamorphosis. Thus, Drosophila larval photobehavior can be used to study control of locomotion. Results: We used targeted neuronal silencing to assess the role of candidate neurons in the regulation of larval photobehavior. Inactivation of DOPA decarboxylase (Ddc) neurons increases the response to light throughout larval development, including during the later stages of the 3rd instar characterized by photoneutral response. Increased response to light is characterized by increase in light-induced direction change and associated pause, and reduction of linear movement. Amongst Ddc neurons, suppression of the activity of corazonergic and serotonergic but not dopaminergic neurons increases the photophobic response observed during 3rd instar stage. Silencing of serotonergic neurons does not disrupt larval locomotion or the response to mechanical stimuli. Reduced serotonin (5-hydroxytryptamine, 5-HT) signaling within serotonergic neurons recapitulates the results obtained with targeted neuronal silencing. Ablation of serotonergic cells in the ventral nerve cord (VNC) does not affect the larval response to light. Similarly, disruption of serotonergic projections that contact the photoreceptor termini in the brain hemispheres does not impact the larval response to light. Finally, pan-neural over-expression of 5-HT1ADro receptors, but not of any other 5-HT receptor subtype, causes a significant decrease in the response to light of 3rd instar larvae. Conclusions: Our data demonstrate that activity of serotonergic and corazonergic neurons contribute to the control of larval locomotion by light. We conclude that this control is carried out by 5-HT neurons located in the brain hemispheres, but does not appear to occur at the photoreceptor level and may be mediated by 5-HT1ADro receptors. These findings provide new insights into the function of 5-HT neurons in Drosophila larval behavior as well as into the mechanisms underlying regulation of larval response to light. http://www.biomedcentral.com/1471-2202/10/66 Veronica Rodriguez Moncalvo Ana Campos BMC Neuroscience 2009, 10:66 2009-06-23T00:00:00Z doi:10.1186/1471-2202-10-66 BMC Neuroscience 1471-2202 10 66 2009-06-23T00:00:00Z PDF Background: Reuptake of synaptic norepinephrine (NE) via the antidepressantsensitiveNE transporter (NET) supports efficient noradrenergic signaling andpresynaptic NE homeostasis. Limited, and somewhat contradictory, informationcurrently describes the axonal transport and localization of NET in neurons. Results: We elucidate NET localization in brain and superior cervical ganglion (SCG)neurons, aided by a new NET monoclonal antibody, subcellular immunoisolationtechniques and quantitative immunofluorescence approaches. We present evidencethat axonal NET extensively colocalizes with syntaxin 1A, and to a limited degree withSCAMP2 and synaptophysin. Intracellular NET in SCG axons and boutons alsoquantitatively segregates from the vesicular monoamine transporter 2 (VMAT2), findingscorroborated by organelle isolation studies. At the surface of SCG boutons, NET residesin both lipid raft and non-lipid raft subdomains and colocalizes with syntaxin 1A. Conclusions: Our findings support the hypothesis that SCG NET is segregated prior totransport from the cell body from proteins comprising large dense core vesicles. Oncelocalized to presynaptic boutons, NET does not recycle via VMAT2-positive, smalldense core vesicles. Finally, once NET reaches presynaptic plasma membranes, thetransporter localizes to syntaxin 1A-rich plasma membrane domains, with a portionfound in cholera toxin-demarcated lipid rafts. Our findings indicate that activity-dependentinsertion of NET into the SCG plasma membrane derives from vesiclesdistinct from those that deliver NE. Moreover, NET is localized in presynapticmembranes in a manner that can take advantage of regulatory processes targeting lipidraft subdomains. http://www.biomedcentral.com/1471-2202/10/65 Heinrich Matthies Qiao Han Angela Shields Jane Wright Jessica Moore Danny Winder Aurelio Galli Randy Blakely BMC Neuroscience 2009, 10:65 2009-06-23T00:00:00Z doi:10.1186/1471-2202-10-65 BMC Neuroscience 1471-2202 10 65 2009-06-23T00:00:00Z PDF Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective loss of motor neurons (MN) in the brain stem and spinal cord. Intracellular disruptions of cytosolic and mitochondrial calcium have been associated with selective MN degeneration, but the underlying mechanisms are not well understood. The present evidence supports a hypothesis that mitochondria are a target of mutant SOD1-mediated toxicity in familial amyotrophic lateral sclerosis (fALS) and intracellular alterations of cytosolic and mitochondrial calcium might aggravate the course of this neurodegenerative disease. In this study, we used a fluorescence charged cool device (CCD) imaging system to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells in an established cellular model of ALS. Results: To gain insights into the molecular mechanisms of SOD1G93A associated motor neuron disease, we simultaneously monitored cytosolic and mitochondrial calcium concentrations in individual cells. Voltage - dependent cytosolic Ca2+ elevations and mitochondria - controlled calcium release mechanisms were monitored after loading cells with fluorescent dyes fura-2 and rhod-2. Interestingly, comparable voltage-dependent cytosolic Ca2+ elevations in WT (SH-SY5YWT) and G93A (SH-SY5YG93A) expressing cells were observed. In contrast, mitochondrial intracellular Ca2+ release responses evoked by bath application of the mitochondrial toxin FCCP were significantly smaller in G93A expressing cells, suggesting impaired calcium stores. Pharmacological experiments further supported the concept that the presence of G93A severely disrupts mitochondrial Ca2+ regulation. Conclusion: In this study, by fluorescence measurement of cytosolic calcium and using simultaneous [Ca2+]i and [Ca2+]mito measurements, we are able to separate and simultaneously monitor cytosolic and mitochondrial calcium concentrations in individual cells an established cellular model of ALS. The primary goals of this paper are (1) method development, and (2) screening for deficits in mutant cells on the single cell level. On the technological level, our method promises to serve as a valuable tool to identify mitochondrial and Ca2+-related defects during G93A-mediated MN degeneration. In addition, our experiments support a model where a specialized interplay between cytosolic calcium profiles and mitochondrial mechanisms contribute to the selective degeneration of neurons in ALS. http://www.biomedcentral.com/1471-2202/10/64 Manoj Jaiswal Wolf--Dieter Zech Miriam Goos Christine Leutbecher Alberto Ferri Annette Zippelius Maria Carri Roland Nau Bernhard Keller BMC Neuroscience 2009, 10:64 2009-06-22T00:00:00Z doi:10.1186/1471-2202-10-64 BMC Neuroscience 1471-2202 10 64 2009-06-22T00:00:00Z PDF