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581. Chronic Administration of a Leupeptin-Derived Calpain Inhibitor Fails to Ameliorate Severe Muscle Pathology in a Canine Model of Duchenne Muscular Dystrophy

Title Tesim:
Chronic Administration of a Leupeptin-Derived Calpain Inhibitor Fails to Ameliorate Severe Muscle Pathology in a Canine Model of Duchenne Muscular Dystrophy
Creator:
Grange, Robert W., Greiner, Hansel, Bogan, Daniel J., Kornegay, Joe N., Childers, Martin K., Bogan, Janet R., and Holder, Melanie
Date of publication:
2012
Abstract Tesim:
Calpains likely play a role in the pathogenesis of Duchenne muscular dystrophy (DMD). Accordingly, calpain inhibition may provide therapeutic benefit to DMD patients. In the present study, we sought to measure benefit from administration of a novel calpain inhibitor, C101, in a canine muscular dystrophy model. Specifically, we tested the hypothesis that treatment with C101 mitigates progressive weakness and severe muscle pathology observed in young dogs with golden retriever muscular dystrophy (GRMD). Young (6-week-old) GRMD dogs were treated daily with either C101 (17 mg/kg twice daily oral dose, n = 9) or placebo (vehicle only, n = 7) for 8 weeks. A battery of functional tests, including tibiotarsal joint angle, muscle/fat composition, and pelvic limb muscle strength were performed at baseline and every 2 weeks during the 8-week study. Results indicate that C101-treated GRMD dogs maintained strength in their cranial pelvic limb muscles (tibiotarsal flexors) while placebo-treated dogs progressively lost strength. However, concomitant improvement was not observed in posterior pelvic limb muscles (tibiotarsal extensors). C101 treatment did not mitigate force drop following repeated eccentric contractions and no improvement was seen in the development of joint contractures, lean muscle mass, or muscle histopathology. Taken together, these data do not support the hypothesis that treatment with C101 mitigates progressive weakness or ameliorates severe muscle pathology observed in young dogs with GRMD.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/4qg7-ha07
Identifier:
PMID: 22291646, Onescience id: c443361cbe68f0933155825fa550f78dc3d6fba8, Publisher DOI: https://doi.org/10.3389/fphar.2011.00089, and PMCID: PMC3253583
ISSN:
1663-9812
Journal Title:
Frontiers in Pharmacology
Journal Volume:
2
Keyword:
calpain, skeletal muscle, muscular dystrophy, canine, protease, and animal
Language Label:
English
Person:
Grange, Robert W., Greiner, Hansel, Bogan, Daniel J., Kornegay, Joe N., Childers, Martin K., Bogan, Janet R., and Holder, Melanie
Rights Statement Label:
In Copyright
Source:
dn39x795x

582. Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol

Title Tesim:
Reducing Auditory Hypersensitivities in Autistic Spectrum Disorder: Preliminary Findings Evaluating the Listening Project Protocol
Creator:
Cook, Edwin H., Porges, Stephen W., Lewis, Gregory F., Bazhenova, Olga V., Sorokin, Yevgeniya, Carlson, Nancy, Heilman, Keri J., and Bal, Elgiz
Date of publication:
2014
Abstract Tesim:
Auditory hypersensitivities are a common feature of autism spectrum disorder (ASD). In the present study, the effectiveness of a novel intervention, the listening project protocol (LPP), was evaluated in two trials conducted with children diagnosed with ASD. LPP was developed to reduce auditory hypersensitivities. LPP is based on a theoretical “neural exercise” model that uses computer altered acoustic stimulation to recruit the neural regulation of middle ear muscles. Features of the intervention stimuli were informed by basic research in speech and hearing sciences that has identified the specific acoustic frequencies necessary to understand speech, which must pass through middle ear structures before being processed by other components of the auditory system. LPP was hypothesized to reduce auditory hypersensitivities by increasing the neural tone to the middle ear muscles to functionally dampen competing sounds in frequencies lower than human speech. The trials demonstrated that LPP, when contrasted to control conditions, selectively reduced auditory hypersensitivities. These findings are consistent with the polyvagal theory, which emphasizes the role of the middle ear muscles in social communication.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/f21k-v162
Identifier:
PMID: 25136545, PMCID: PMC4117928, Publisher DOI: https://doi.org/10.3389/fped.2014.00080, and Onescience id: 99fe75c178dae2758404616ad285fb909d427526
ISSN:
2296-2360
Journal Title:
Frontiers in Pediatrics
Journal Volume:
2
Keyword:
auditory hypersensitivities, polyvagal theory, autism, listening, and social engagement behaviors
Language Label:
English
Person:
Cook, Edwin H., Porges, Stephen W., Lewis, Gregory F., Bazhenova, Olga V., Sorokin, Yevgeniya, Carlson, Nancy, Heilman, Keri J., and Bal, Elgiz
Rights Statement Label:
In Copyright
Source:
n870zz44m

583. Robust estimation of group-wise cortical correspondence with an application to macaque and human neuroimaging studies

Title Tesim:
Robust estimation of group-wise cortical correspondence with an application to macaque and human neuroimaging studies
Creator:
Yoo, Sang W., Shi, Yundi, Kim, Sun H., Niethammer, Marc, Styner, Martin A., Seong, Joon-Kyung, Evans, Alan, Sanchez, Mar, and Lyu, Ilwoo
Date of publication:
2015
Abstract Tesim:
We present a novel group-wise registration method for cortical correspondence for local cortical thickness analysis in human and non-human primate neuroimaging studies. The proposed method is based on our earlier template based registration that estimates a continuous, smooth deformation field via sulcal curve-constrained registration employing spherical harmonic decomposition of the deformation field. This pairwise registration though results in a well-known template selection bias, which we aim to overcome here via a group-wise approach. We propose the use of an unbiased ensemble entropy minimization following the use of the pairwise registration as an initialization. An individual deformation field is then iteratively updated onto the unbiased average. For the optimization, we use metrics specific for cortical correspondence though all of these are straightforwardly extendable to the generic setting: The first focused on optimizing the correspondence of automatically extracted sulcal landmarks and the second on that of sulcal depth property maps. We further propose a robust entropy metric and a hierarchical optimization by employing spherical harmonic basis orthogonality. We also provide the detailed methodological description of both our earlier work and the proposed method with a set of experiments on a population of human and non-human primate subjects. In the experiment, we have shown that our method achieves superior results on consistency through quantitative and visual comparisons as compared to the existing methods.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/6sg1-xv43
Identifier:
Publisher DOI: https://doi.org/10.3389/fnins.2015.00210, PMCID: PMC4462677, Onescience id: 4f574bff5c5bffd43cbe6f395c6100eecf7f5ec2, and PMID: 26113807
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
9
Keyword:
sulcal curve, spherical harmonics, Group-wise registration, Entropy minimization, Surface Registration, and cortical surface
Language Label:
English
Person:
Yoo, Sang W., Shi, Yundi, Kim, Sun H., Niethammer, Marc, Styner, Martin A., Seong, Joon-Kyung, Evans, Alan, Sanchez, Mar, and Lyu, Ilwoo
Rights Statement Label:
In Copyright
Source:
00000604b

584. Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders

Title Tesim:
Targeting central melanocortin receptors: a promising novel approach for treating alcohol abuse disorders
Creator:
Navarro, Montserrat, Thiele, Todd E., and Olney, Jeffrey J.
Date of publication:
2014
Abstract Tesim:
The melanocortin (MC) peptides are produced centrally by propiomelanocortin (POMC) neurons within the arcuate nucleus of the hypothalamus and act through five seven-transmembrane G-protein coupled melanocortin receptor (MCR) subtypes. The MC3R and MC4R subtypes, the most abundant central MCRs, are widely expressed in brain regions known to modulate neurobiological responses to ethanol, including regions of the hypothalamus and extended amygdala. Agouti-related protein (AgRP), also produced in the arcuate nucleus, is secreted in terminals expressing MCRs and functions as an endogenous MCR antagonist. This review highlights recent genetic and pharmacological findings that have implicated roles for the MC and AgRP systems in modulating ethanol consumption. Ethanol consumption is associated with significant alterations in the expression levels of various MC peptides/protein, which suggests that ethanol-induced perturbations of MC/AgRP signaling may modulate excessive ethanol intake. Consistently, MCR agonists decrease, and AgRP increases, ethanol consumption in mice. MCR agonists fail to blunt ethanol intake in mutant mice lacking the MC4R, suggesting that the protective effects of MCR agonists are modulated by the MC4R. Interestingly, recent evidence reveals that MCR agonists are more effective at blunting binge-like ethanol intake in mutant mice lacking the MC3R, suggesting that the MC3R has opposing effects on the MC4R. Finally, mutant mice lacking AgRP exhibit blunted voluntary and binge-like ethanol drinking, consistent with pharmacological studies. Collectively, these preclinical observations provide compelling evidence that compounds that target the MC system may provide therapeutic value for treating alcohol abuse disorders and that the utilization of currently available MC-targeting compounds- such as those being used to treat eating disorders- may be used as effective treatments to this end.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/smy7-j586
Identifier:
Onescience id: d8b910ee1fa050821c3a9217894b07158dd67724, Publisher DOI: https://doi.org/10.3389/fnins.2014.00128, PMID: 24917782, and PMCID: PMC4042890
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
8
Keyword:
Brain, Arcuate Nucleus of Hypothalamus, Mus musculus, Neurons, Mc4r, Drinking, Agouti-Related Protein, Eating Disorders, AGRP, Proteins, AgRP, Therapeutics, Receptors, G-Protein-Coupled, MC4R, Mc3r, Ethanol, Agrp, melanocortin, Pomc, α-MSH, MC3R, Amygdala, Hypothalamus, Melanocortins, POMC, Receptors, Melanocortin, Peptides, and Alcoholism
Language Label:
English
Person:
Navarro, Montserrat, Thiele, Todd E., and Olney, Jeffrey J.
Rights Statement Label:
In Copyright
Source:
zc77sx60d

585. Individual differences in social information gathering revealed through Bayesian hierarchical models

Title Tesim:
Individual differences in social information gathering revealed through Bayesian hierarchical models
Creator:
Watson, Karli K., Ebitz, R. Becket, Platt, Michael L., Klein, Jeffrey T., and Pearson, John M.
Date of publication:
2013
Abstract Tesim:
As studies of the neural circuits underlying choice expand to include more complicated behaviors, analysis of behaviors elicited in laboratory paradigms has grown increasingly difficult. Social behaviors present a particular challenge, since inter- and intra-individual variation are expected to play key roles. However, due to limitations on data collection, studies must often choose between pooling data across all subjects or using individual subjects' data in isolation. Hierarchical models mediate between these two extremes by modeling individual subjects as drawn from a population distribution, allowing the population at large to serve as prior information about individuals' behavior. Here, we apply this method to data collected across multiple experimental sessions from a set of rhesus macaques performing a social information valuation task. We show that, while the values of social images vary markedly between individuals and between experimental sessions for the same individual, individuals also differentially value particular categories of social images. Furthermore, we demonstrate covariance between values for image categories within individuals and find evidence suggesting that magnitudes of stimulus values tend to diminish over time.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/6c93-5w33
Identifier:
Onescience id: b7412be4542eec1f9005f4441250f0f09e4ea448, PMCID: PMC3771214, Publisher DOI: https://doi.org/10.3389/fnins.2013.00165, and PMID: 24062635
ISSN:
1662-4548 and 1662-453X
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
foraging, pay-per-view, information foraging, Bayesian Models, and social neuroscience
Language Label:
English
Person:
Watson, Karli K., Ebitz, R. Becket, Platt, Michael L., Klein, Jeffrey T., and Pearson, John M.
Rights Statement Label:
In Copyright
Source:
s7526k777

586. Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution

Title Tesim:
Brain immune interactions and air pollution: macrophage inhibitory factor (MIF), prion cellular protein (PrPC), Interleukin-6 (IL-6), interleukin 1 receptor antagonist (IL-1Ra), and interleukin-2 (IL-2) in cerebrospinal fluid and MIF in serum differentiate urban children exposed to severe vs. low air pollution
Creator:
Chang, Jing, Zhu, Hongtu, Torres-Jardón, Ricardo, Aragón-Flores, Mariana, Thompson, Charles, Chao, Chih-kai, D'Angiulli, Amedeo, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, Kavanaugh, Michael, and Cross, Janet V.
Date of publication:
2013
Abstract Tesim:
Mexico City Metropolitan Area children chronically exposed to high concentrations of air pollutants exhibit an early brain imbalance in genes involved in oxidative stress, inflammation, innate and adaptive immune responses along with accumulation of misfolded proteins observed in the early stages of Alzheimer and Parkinson's diseases. A complex modulation of serum cytokines and chemokines influences children's brain structural and gray/white matter volumetric responses to air pollution. The search for biomarkers associating systemic and CNS inflammation to brain growth and cognitive deficits in the short term and neurodegeneration in the long-term is our principal aim. We explored and compared a profile of cytokines, chemokines (Multiplexing LASER Bead Technology) and Cellular prion protein (PrPC) in normal cerebro-spinal-fluid (CSF) of urban children with high vs. low air pollution exposures. PrPC and macrophage inhibitory factor (MIF) were also measured in serum. Samples from 139 children ages 11.91 ± 4.2 years were measured. Highly exposed children exhibited significant increases in CSF MIF (p = 0.002), IL6 (p = 0.006), IL1ra (p = 0.014), IL-2 (p = 0.04), and PrPC (p = 0.039) vs. controls. MIF serum concentrations were higher in exposed children (p = 0.009). Our results suggest CSF as a MIF, IL6, IL1Ra, IL-2, and PrPC compartment that can possibly differentiate air pollution exposures in children. MIF, a key neuro-immune mediator, is a potential biomarker bridge to identify children with CNS inflammation. Fine tuning of immune-to-brain communication is crucial to neural networks appropriate functioning, thus the short and long term effects of systemic inflammation and dysregulated neural immune responses are of deep concern for millions of exposed children. Defining the linkage and the health consequences of the brain / immune system interactions in the developing brain chronically exposed to air pollutants ought to be of pressing importance for public health.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/yf7g-xc18
Identifier:
PMCID: PMC3794301, Publisher DOI: https://doi.org/10.3389/fnins.2013.00183, PMID: 24133408, and Onescience id: bd61be773f3d2cc47e4fc1155a9f798c61d050e8
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
Serum, Parkinson Disease, Receptors, Interleukin-1, Brain, Chemokines, Biological Markers, IL2, Immune System, Interleukin-6, Prions, Proteins, IL1RN, Cytokines, Growth, Interleukin-2, IL6, PRNP, Protein C, Cerebrospinal Fluid, Adaptive Immunity, Air Pollutants, Genes, White Matter, Interleukin 1 Receptor Antagonist Protein, Cities, Macrophages, and Inflammation
Language Label:
English
Person:
Chang, Jing, Zhu, Hongtu, Torres-Jardón, Ricardo, Aragón-Flores, Mariana, Thompson, Charles, Chao, Chih-kai, D'Angiulli, Amedeo, Franco-Lira, Maricela, Calderón-Garcidueñas, Lilian, Kavanaugh, Michael, and Cross, Janet V.
Rights Statement Label:
In Copyright
Source:
47429g81z

587. A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia

Title Tesim:
A multi-site resting state fMRI study on the amplitude of low frequency fluctuations in schizophrenia
Creator:
Turner, Jessica A
Date of publication:
2013
Abstract Tesim:
Background: This multi-site study compares resting state fMRI amplitude of low frequency fluctuations (ALFF) and fractional ALFF (fALFF) between patients with schizophrenia (SZ) and healthy controls (HC).Methods: Eyes-closed resting fMRI scans (5:38 min; n = 306, 146 SZ) were collected from 6 Siemens 3T scanners and one GE 3T scanner. Imaging data were pre-processed using an SPM pipeline. Power in the low frequency band (0.01–0.08 Hz) was calculated both for the original pre-processed data as well as for the pre-processed data after regressing out the six rigid-body motion parameters, mean white matter (WM) and cerebral spinal fluid (CSF) signals. Both original and regressed ALFF and fALFF measures were modeled with site, diagnosis, age, and diagnosis × age interactions.Results: Regressing out motion and non-gray matter signals significantly decreased fALFF throughout the brain as well as ALFF in the cortical edge, but significantly increased ALFF in subcortical regions. Regression had little effect on site, age, and diagnosis effects on ALFF, other than to reduce diagnosis effects in subcortical regions. There were significant effects of site across the brain in all the analyses, largely due to vendor differences. HC showed greater ALFF in the occipital, posterior parietal, and superior temporal lobe, while SZ showed smaller clusters of greater ALFF in the frontal and temporal/insular regions as well as in the caudate, putamen, and hippocampus. HC showed greater fALFF compared with SZ in all regions, though subcortical differences were only significant for original fALFF.Conclusions: SZ show greater eyes-closed resting state low frequency power in frontal cortex, and less power in posterior lobes than do HC; fALFF, however, is lower in SZ than HC throughout the cortex. These effects are robust to multi-site variability. Regressing out physiological noise signals significantly affects both total and fALFF measures, but does not affect the pattern of case/control differences.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/qnng-w562
Identifier:
PMID: 23964193, PMCID: PMC3737471, Onescience id: ce2ee538d9cc61e2c9919b8c3a7c54ea0fd2b990, and Publisher DOI: https://doi.org/10.3389/fnins.2013.00137
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
7
Keyword:
multi-site study, LFO, Schizophrenia, ALFF, resting state fMRI, and effect size
Language Label:
English
Person:
Turner, Jessica A
Rights Statement Label:
In Copyright
Source:
3n2044934

588. Inflammasome-IL-1β Signaling Mediates Ethanol Inhibition of Hippocampal Neurogenesis

Title Tesim:
Inflammasome-IL-1β Signaling Mediates Ethanol Inhibition of Hippocampal Neurogenesis
Creator:
Zou, Jian and Crews, Fulton T.
Date of publication:
2012
Abstract Tesim:
Regulation of hippocampal neurogenesis is poorly understood, but appears to contribute to mood and cognition. Ethanol and neuroinflammation are known to reduce neurogenesis. We have found that ethanol induces neuroinflammation supporting the hypothesis that ethanol induction of neuroinflammation contributes to ethanol inhibition of neurogenesis. To identify the key proinflammatory molecule that may be responsible for ethanol-impaired neurogenesis we used an ex vivo model of organotypic hippocampal-entorhinal cortex brain slice cultures. Here, we demonstrated a key role of proinflammatory cytokine IL-1β signaling in mediating ethanol inhibition of neurogenesis. Ethanol inhibition of neurogenesis was reversed by neutralizing antibody to IL-1β or blockade of the IL-1β receptor with antagonist IL-1RIa. Ethanol-impaired neurogenesis is associated with strong induction of IL-1β and inflammasome proteins NALP1 and NALP3 in both neurons and astrocytes. Blockade of IL-1β synthesis with inflammasome inhibitors Parthenolide and Bay11708 significantly reversed ethanol inhibited neurogenesis. Furthermore, we also found that IL-1β and inflammasome proteins NALP1 and NALP3 are increased in hippocampal neurons and astrocytes in postmortem alcoholic human brain. Together, these novel findings demonstrate that targeting inflammasome-IL-1β signaling can normalize ethanol-impaired hippocampal neurogenesis, which may have therapeutic implications for treatment of cognitive impairment associated with hippocampal dysfunction in alcoholics.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/vmdr-3t34
Identifier:
Publisher DOI: https://doi.org/10.3389/fnins.2012.00077, PMID: 22661925, PMCID: PMC3362805, and Onescience id: 6b1de41ac65774f5d5b99c1eda62bb14cf4cdcd4
ISSN:
1662-453X and 1662-4548
Journal Title:
Frontiers in Neuroscience
Journal Volume:
6
Keyword:
alcohol, neuroprogenitors, inflammasomes, neurogenesis, IL-1β, and brain slice culture
Language Label:
English
Person:
Zou, Jian and Crews, Fulton T.
Rights Statement Label:
In Copyright
Source:
vx021n55p

589. Ethanol Activation of Protein Kinase A Regulates GABAA Receptor Subunit Expression in the Cerebral Cortex and Contributes to Ethanol-Induced Hypnosis

Title Tesim:
Ethanol Activation of Protein Kinase A Regulates GABAA Receptor Subunit Expression in the Cerebral Cortex and Contributes to Ethanol-Induced Hypnosis
Creator:
Morrow, A. Leslie, O’Buckley, Todd K., Kumar, Sandeep, Ren, Qinglu, Werner, David F., Gigante, Eduardo D., Santerre, Jessica L., and Beckley, Jonathon H.
Date of publication:
2012
Abstract Tesim:
Protein kinases are implicated in neuronal cell functions such as modulation of ion channel function, trafficking, and synaptic excitability. Both protein kinase C (PKC) and A (PKA) are involved in regulation of γ-aminobutyric acid type A (GABAA) receptors through phosphorylation. However, the role of PKA in regulating GABAA receptors (GABAA-R) following acute ethanol exposure is not known. The present study investigated the role of PKA in the effects of ethanol on GABAA-R α1 subunit expression in rat cerebral cortical P2 synaptosomal fractions. Additionally, GABA-related behaviors were examined. Rats were administered ethanol (2.0–3.5 g/kg) or saline and PKC, PKA, and GABAA-R α1 subunit levels were measured by western blot analysis. Ethanol (3.5 g/kg) transiently increased GABAA-R α1 subunit expression and PKA RIIβ subunit expression at similar time points whereas PKA RIIα was increased at later time points. In contrast, PKC isoform expression remained unchanged. Notably, lower ethanol doses (2.0 g/kg) had no effect on GABAA-R α1 subunit levels, although PKA type II regulatory subunits RIIα and RIIβ were increased at 10 and 60 min when PKC isozymes are also known to be elevated. To determine if PKA activation was responsible for the ethanol-induced elevation of GABAA-R α1 subunits, the PKA antagonist H89 was administered to rats prior to ethanol exposure. H89 administration prevented ethanol-induced increases in GABAA-R α1 subunit expression. Moreover, increasing PKA activity intracerebroventricularly with Sp-cAMP prior to a hypnotic dose of ethanol increased ethanol-induced loss of righting reflex (LORR) duration. This effect appears to be mediated in part by GABAA-R as increasing PKA activity also increased the duration of muscimol-induced LORR. Overall, these data suggest that PKA mediates ethanol-induced GABAA-R expression and contributes to behavioral effects of ethanol involving GABAA-R.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/tw5a-7735
Identifier:
Onescience id: b034646923368dd44c12d13b4fe0f7d6261408f3, PMID: 22509146, PMCID: PMC3321501, and Publisher DOI: https://doi.org/10.3389/fnins.2012.00044
ISSN:
1662-4548 and 1662-453X
Journal Title:
Frontiers in Neuroscience
Journal Volume:
6
Keyword:
loss of righting reflex, GABA, receptors, PKA, ethanol, and PKC
Language Label:
English
Person:
Morrow, A. Leslie, O’Buckley, Todd K., Kumar, Sandeep, Ren, Qinglu, Werner, David F., Gigante, Eduardo D., Santerre, Jessica L., and Beckley, Jonathon H.
Rights Statement Label:
In Copyright
Source:
6t053p23h

590. Subject–Motion Correction in HARDI Acquisitions: Choices and Consequences

Title Tesim:
Subject–Motion Correction in HARDI Acquisitions: Choices and Consequences
Creator:
Vachet, Clement, Leppert, Ilana R., Piven, Joseph, Gerig, Guido, Styner, Martin, Pike, G. Bruce, Elhabian, Shireen, and Gur, Yaniv
Date of publication:
2014
Abstract Tesim:
Diffusion-weighted imaging (DWI) is known to be prone to artifacts related to motion originating from subject movement, cardiac pulsation, and breathing, but also to mechanical issues such as table vibrations. Given the necessity for rigorous quality control and motion correction, users are often left to use simple heuristics to select correction schemes, which involves simple qualitative viewing of the set of DWI data, or the selection of transformation parameter thresholds for detection of motion outliers. The scientific community offers strong theoretical and experimental work on noise reduction and orientation distribution function (ODF) reconstruction techniques for HARDI data, where post-acquisition motion correction is widely performed, e.g., using the open-source DTIprep software (1), FSL (the FMRIB Software Library) (2), or TORTOISE (3). Nonetheless, effects and consequences of the selection of motion correction schemes on the final analysis, and the eventual risk of introducing confounding factors when comparing populations, are much less known and far beyond simple intuitive guessing. Hence, standard users lack clear guidelines and recommendations in practical settings. This paper reports a comprehensive evaluation framework to systematically assess the outcome of different motion correction choices commonly used by the scientific community on different DWI-derived measures. We make use of human brain HARDI data from a well-controlled motion experiment to simulate various degrees of motion corruption and noise contamination. Choices for correction include exclusion/scrubbing or registration of motion corrupted directions with different choices of interpolation, as well as the option of interpolation of all directions. The comparative evaluation is based on a study of the impact of motion correction using four metrics that quantify (1) similarity of fiber orientation distribution functions (fODFs), (2) deviation of local fiber orientations, (3) global brain connectivity via graph diffusion distance (GDD), and (4) the reproducibility of prominent and anatomically defined fiber tracts. Effects of various motion correction choices are systematically explored and illustrated, leading to a general conclusion of discouraging users from setting ad hoc thresholds on the estimated motion parameters beyond which volumes are claimed to be corrupted.
Resource type:
Article
Deposit Record:
http://windsor.libint.unc.edu:8181/fcrepo/rest/prod/f8/ca/d5/63/f8cad563-9b67-4053-a6f6-f544764d92b7
Type:
http://purl.org/dc/dcmitype/Text
DOI:
https://doi.org/10.17615/gwpa-8624
Identifier:
Publisher DOI: https://doi.org/10.3389/fneur.2014.00240, PMCID: PMC4260507, PMID: 25538672, and Onescience id: c0f8f2d1b623803edb9f158dcb19403153e06763
ISSN:
1664-2295
Journal Title:
Frontiers in Neurology
Journal Volume:
5
Keyword:
subject motion, Motion Correction, fiber orientations, HARDI, impact quantification, tractography comparison, and orientation distribution functions
Language Label:
English
Person:
Vachet, Clement, Leppert, Ilana R., Piven, Joseph, Gerig, Guido, Styner, Martin, Pike, G. Bruce, Elhabian, Shireen, and Gur, Yaniv
Rights Statement Label:
In Copyright
Source:
6395wf384