Amina S. Woods, Ph.D.

@article{Jackson:2018aa,

title = {AP-MALDI Mass Spectrometry Imaging of Gangliosides Using 2,6-Dihydroxyacetophenone.},

author = {Shelley N Jackson and Ludovic Muller and Aurelie Roux and Berk Oktem and Eugene Moskovets and Vladimir M Doroshenko and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29549666},

doi = {10.1007/s13361-018-1928-8},

issn = {1879-1123 (Electronic); 1044-0305 (Linking)},

year  = {2018},

date = {2018-03-16},

journal = {J Am Soc Mass Spectrom},

address = {Integrative Neuroscience, NIDA IRP, NIH, 333 Cassell Drive, Room 1119, Baltimore, MD, 21224, USA. shjackson@intra.nida.nih.gov.},

abstract = {Matrix-assisted laser/desorption ionization (MALDI) mass spectrometry imaging (MSI) is widely used as a unique tool to record the distribution of a large range of biomolecules in tissues. 2,6-Dihydroxyacetophenone (DHA) matrix has been shown to provide efficient ionization of lipids, especially gangliosides. The major drawback for DHA as it applies to MS imaging is that it sublimes under vacuum (low pressure) at the extended time necessary to complete both high spatial and mass resolution MSI studies of whole organs. To overcome the problem of sublimation, we used an atmospheric pressure (AP)-MALDI source to obtain high spatial resolution images of lipids in the brain using a high mass resolution mass spectrometer. Additionally, the advantages of atmospheric pressure and DHA for imaging gangliosides are highlighted. The imaging of [M-H](-) and [M-H2O-H](-) mass peaks for GD1 gangliosides showed different distribution, most likely reflecting the different spatial distribution of GD1a and GD1b species in the brain. Graphical Abstract .},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Agnati:2018aa,

title = {The brain as a "hyper-network": the key role of neural networks as main producers of the integrated brain actions especially via the "broadcasted" neuroconnectomics.},

author = {Luigi F Agnati and Manuela Marcoli and Guido Maura and Amina Woods and Diego Guidolin},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29427068},

doi = {10.1007/s00702-018-1855-7},

issn = {1435-1463 (Electronic); 0300-9564 (Linking)},

year  = {2018},

date = {2018-02-09},

journal = {J Neural Transm (Vienna)},

address = {Department of Diagnostic, Clinical Medicine and Public Health, University of Modena and Reggio Emilia, Modena, Italy. luigi.agnati@gmail.com.},

abstract = {Investigations of brain complex integrative actions should consider beside neural networks, glial, extracellular molecular, and fluid channels networks. The present paper proposes that all these networks are assembled into the brain hyper-network that has as fundamental components, the tetra-partite synapses, formed by neural, glial, and extracellular molecular networks. Furthermore, peri-synaptic astrocytic processes by modulating the perviousness of extracellular fluid channels control the signals impinging on the tetra-partite synapses. It has also been surmised that global signalling via astrocytes networks and highly pervasive signals, such as electromagnetic fields (EMFs), allow the appropriate integration of the various networks especially at crucial nodes level, the tetra-partite synapses. As a matter of fact, it has been shown that astrocytes can form gap-junction-coupled syncytia allowing intercellular communication characterised by a rapid and possibly long-distance transfer of signals. As far as the EMFs are concerned, the concept of broadcasted neuroconnectomics (BNC) has been introduced to describe highly pervasive signals involved in resetting the information handling of brain networks at various miniaturisation levels. In other words, BNC creates, thanks to the EMFs, generated especially by neurons, different assemblages among the various networks forming the brain hyper-network. Thus, it is surmised that neuronal networks are the "core components" of the brain hyper-network that has as special "nodes" the multi-facet tetra-partite synapses. Furthermore, it is suggested that investigations on the functional plasticity of multi-partite synapses in response to BNC can be the background for a new understanding and perhaps a new modelling of brain morpho-functional organisation and integrative actions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Barbacci:2017aa,

title = {Mass Spectrometric Imaging of Ceramide Biomarkers Tracks Therapeutic Response in Traumatic Brain Injury.},

author = {Damon C Barbacci and Aurelie Roux and Ludovic Muller and Shelley N Jackson and Jeremy Post and Kathrine Baldwin and Barry Hoffer and Carey D Balaban and Albert J Schultz and Shawn Gouty and Brian M Cox and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28745861},

doi = {10.1021/acschemneuro.7b00189},

issn = {1948-7193 (Electronic); 1948-7193 (Linking)},

year  = {2017},

date = {2017-10-18},

journal = {ACS Chem Neurosci},

volume = {8},

number = {10},

pages = {2266--2274},

address = {Ionwerks, Inc , Houston, Texas 77002, United States.},

abstract = {Traumatic brain injury (TBI) is a serious public health problem and the leading cause of death in children and young adults. It also contributes to a substantial number of cases of permanent disability. As lipids make up over 50% of the brain mass and play a key role in both membrane structure and cell signaling, their profile is of particular interest. In this study, we show that advanced mass spectrometry imaging (MSI) has sufficient technical accuracy and reproducibility to demonstrate the anatomical distribution of 50 mum diameter microdomains that show changes in brain ceramide levels in a rat model of controlled cortical impact (CCI) 3 days post injury with and without treatment. Adult male Sprague-Dawley rats received one strike and were euthanized 3 days post trauma. Brain MS images showed increase in ceramides in CCI animals compared to control as well as significant reduction in ceramides in CCI treated animals, demonstrating therapeutic effect of a peptide agonist. The data also suggests the presence of diffuse changes outside of the injured area. These results shed light on the extent of biochemical and structural changes in the brain after traumatic brain injury and could help to evaluate the efficacy of treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Muller:2017aa,

title = {Laser Desorption/Ionization Mass Spectrometric Imaging of Endogenous Lipids from Rat Brain Tissue Implanted with Silver Nanoparticles.},

author = {Ludovic Muller and Kathrine Baldwin and Damon C Barbacci and Shelley N Jackson and Aurelie Roux and Carey D Balaban and Bruce E Brinson and Michael I McCully and Ernest K Lewis and Albert J Schultz and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/28432654},

doi = {10.1007/s13361-017-1665-4},

issn = {1879-1123 (Electronic); 1044-0305 (Linking)},

year  = {2017},

date = {2017-08-01},

journal = {J Am Soc Mass Spectrom},

volume = {28},

number = {8},

pages = {1716--1728},

address = {Structural Biology Unit, NIDA IRP, NIH, Baltimore, MD, USA.},

abstract = {Mass spectrometry imaging (MSI) of tissue implanted with silver nanoparticulate (AgNP) matrix generates reproducible imaging of lipids in rodent models of disease and injury. Gas-phase production and acceleration of size-selected 8 nm AgNP is followed by controlled ion beam rastering and soft landing implantation of 500 eV AgNP into tissue. Focused 337 nm laser desorption produces high quality images for most lipid classes in rat brain tissue (in positive mode: galactoceramides, diacylglycerols, ceramides, phosphatidylcholines, cholesteryl ester, and cholesterol, and in negative ion mode: phosphatidylethanolamides, sulfatides, phosphatidylinositol, and sphingomyelins). Image reproducibility in serial sections of brain tissue is achieved within <10% tolerance by selecting argentated instead of alkali cationized ions. The imaging of brain tissues spotted with pure standards was used to demonstrate that Ag cationized ceramide and diacylglycerol ions are from intact, endogenous species. In contrast, almost all Ag cationized fatty acid ions are a result of fragmentations of numerous lipid types having the fatty acid as a subunit. Almost no argentated intact fatty acid ions come from the pure fatty acid standard on tissue. Graphical Abstract .},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cervetto:2017aa,

title = {A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.},

author = {Chiara Cervetto and Arianna Venturini and Mario Passalacqua and Diego Guidolin and Susanna Genedani and Kjell Fuxe and Dasiel O Borroto-Esquela and Pietro Cortelli and Amina Woods and Guido Maura and Manuela Marcoli and Luigi F Agnati},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27896809},

doi = {10.1111/jnc.13885},

issn = {1471-4159 (Electronic); 0022-3042 (Linking)},

year  = {2017},

date = {2017-01-01},

journal = {J Neurochem},

volume = {140},

number = {2},

pages = {268--279},

address = {Section of Pharmacology and Toxicology, Department of Pharmacy, University of Genova, Genova, Italy.},

abstract = {Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Roux:2016aa,

title = {Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury.},

author = {Aurelie Roux and Ludovic Muller and Shelley N Jackson and Jeremy Post and Katherine Baldwin and Barry Hoffer and Carey D Balaban and Damon Barbacci and Albert J Schultz and Shawn Gouty and Brian M Cox and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/26872743},

doi = {10.1016/j.jneumeth.2016.02.004},

issn = {1872-678X (Electronic); 0165-0270 (Linking)},

year  = {2016},

date = {2016-10-15},

journal = {J Neurosci Methods},

volume = {272},

pages = {19--32},

address = {Structural Biology Unit, Integrative Neuroscience Branch, NIH/NIDA-IRP, Baltimore, MD 21224, United States.},

abstract = {BACKGROUND: Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion. NEW METHOD: A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50mum diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI. RESULTS: Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury. COMPARISON WITH EXISTING METHOD(S): Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain. CONCLUSIONS: Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Roux:2016ab,

title = {Ethanol Induced Brain Lipid Changes in Mice Assessed by Mass Spectrometry.},

author = {Aurelie Roux and Shelley N Jackson and Ludovic Muller and Damon Barbacci and Joseph O'Rourke and Panayotis K Thanos and Nora D Volkow and Carey Balaban and Albert J Schultz and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/27269520},

doi = {10.1021/acschemneuro.6b00120},

issn = {1948-7193 (Electronic); 1948-7193 (Linking)},

year  = {2016},

date = {2016-08-17},

journal = {ACS Chem Neurosci},

volume = {7},

number = {8},

pages = {1148--1156},

address = {Structural Biology Unit, NIDA IRP, NIH , Baltimore, Maryland 21224, United States.},

abstract = {Alcohol abuse is a chronic disease characterized by the consumption of alcohol at a level that interferes with physical and mental health and causes serious and persistent changes in the brain. Lipid metabolism is of particular interest due to its high concentration in the brain. Lipids are the main component of cell membranes, are involved in cell signaling, signal transduction, and energy storage. In this study, we analyzed lipid composition of chronically ethanol exposed mouse brains. Juvenile (JUV) and adult (ADU) mice were placed on a daily limited-access ethanol intake model for 52 days. After euthanasia, brains were harvested, and total lipids were extracted from brain homogenates. Samples were analyzed using high resolution mass spectrometry and processed by multivariate and univariate statistical analysis. Significant lipid changes were observed in different classes including sphingolipids, fatty acids, lysophosphatidylcholines, and other glycerophospholipids.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Roux:2015aa,

title = {Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents.},

author = {Aurelie Roux and Ludovic Muller and Shelley N Jackson and Katherine Baldwin and Virginia Womack and John G Pagiazitis and Joseph R O'Rourke and Panayotis K Thanos and Carey Balaban and Albert J Schultz and Nora D Volkow and Amina S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/25387107},

doi = {10.1021/cn500174c},

issn = {1948-7193 (Electronic); 1948-7193 (Linking)},

year  = {2015},

date = {2015-02-18},

journal = {ACS Chem Neurosci},

volume = {6},

number = {2},

pages = {247--259},

address = {Structural Biology Unit, NIDA IRP, NIH , Baltimore, Maryland 21224, United States.},

abstract = {Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 mum spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tovo-Rodrigues:2014aa,

title = {Functional characterization of G-protein-coupled receptors: a bioinformatics approach.},

author = {L Tovo-Rodrigues and A Roux and M H Hutz and L A Rohde and A S Woods},

url = {https://www.ncbi.nlm.nih.gov/pubmed/24997265},

doi = {10.1016/j.neuroscience.2014.06.049},

issn = {1873-7544 (Electronic); 0306-4522 (Linking)},

year  = {2014},

date = {2014-09-26},

journal = {Neuroscience},

volume = {277},

pages = {764--779},

address = {Department of Genetics, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil; Structural Biology Unit, Integrative Neuroscience Branch, NIDA IRP, NIH, MD, United States.},

abstract = {Complex molecular and cellular mechanisms regulate G protein-coupled receptors (GPCRs). It is suggested that proteins intrinsically disordered regions (IDRs) are to play a role in GPCR's intra and extracellular regions plasticity, due to their potential for post-translational modification and interaction with other proteins. These regions are defined as lacking a stable three-dimensional (3D) structure. They are rich in hydrophilic and charged, amino acids and are capable to assume different conformations which allow them to interact with multiple partners. In this study we analyzed 75 GPCR involved in synaptic transmission using computational tools for sequence-based prediction of IDRs within a protein. We also evaluated putative ligand-binding motifs using receptor sequences. The disorder analysis indicated that neurotransmitter GPCRs have a significant amount of disorder in their N-terminus, third intracellular loop (3IL) and C-terminus. About 31%, 39% and 53% of human GPCR involved in synaptic transmission are disordered in these regions. Thirty-three percent of receptors show at least one predicted PEST motif, this being statistically greater than the estimate for the rest of human GPCRs. About 90% of the receptors had at least one putative site for dimerization in their 3IL or C-terminus. ELM instances sampled in these domains were 14-3-3, SH3, SH2 and PDZ motifs. In conclusion, the increased flexibility observed in GPCRs, added to the enrichment of linear motifs, PEST and heteromerization sites, may be critical for the nervous system's functional plasticity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Woods:2013aa,

title = {How adenylate cyclase choreographs the pas de deux of the receptors heteromerization dance.},

author = {A S Woods and S N Jackson},

url = {https://www.ncbi.nlm.nih.gov/pubmed/23434492},

doi = {10.1016/j.neuroscience.2013.02.006},

issn = {1873-7544 (Electronic); 0306-4522 (Linking)},

year  = {2013},

date = {2013-05-15},

journal = {Neuroscience},

volume = {238},

pages = {335--344},

address = {Structural Biology Unit, Integrative Neuroscience Branch, NIDA IRP, NIH, MD, United States. awoods@mail.nih.gov},

abstract = {Our work suggests that heteromer formation, mainly involves linear motifs (LMs) found in disordered regions of proteins. Local disorder imparts plasticity to LMs. Most molecular recognition of proteins occurs between short linear segments, known as LMs. Interaction of short continuous epitopes is not constrained by sequence and has the advantage of resulting in interactions with micromolar affinities which suit transient, reversible complexes such as receptor heteromers. Electrostatic interactions between epitopes of the G-protein coupled receptors (GPCR) involved, are the key step in driving heteromer formation forward. The first step in heteromerization, involves phosphorylating Ser/Thr in an epitope containing a casein kinase 1/2-consensus site. Our data suggest that dopaminergic neurotransmission, through cAMP-dependent protein kinase A (PKA) slows down heteromerization. The negative charge, acquired by the phosphorylation of a Ser/Thr in a PKA consensus site in the Arg-rich epitope, affects the activity of the receptors involved in heteromerization by causing allosteric conformational changes, due to the repulsive effect generated by the negatively charged phosphate. In addition to modulating heteromerization, it affects the stability of the heteromers' interactions and their binding affinity. So here we have an instance where phosphorylation is not just an on/off switch, instead by weakening the noncovalent bond, heteromerization acts like a rheostat that controls the stability of the heteromer through activation or inhibition of adenylate cyclase by the neurotransmitter Dopamine depending on which Dopamine receptor it docks at.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}