Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 815

Publication Record

Connections

Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150 Deacetylation by Axonal HDAC1.
Pathak A, Stanley EM, Hickman FE, Wallace N, Brewer B, Li D, Gluska S, Perlson E, Fuhrmann S, Akassoglou K, Bronfman F, Casaccia P, Burnette DT, Carter BD
(2018) Dev Cell 46: 376-387.e7
MeSH Terms: Animals, Axonal Transport, Axons, Dynactin Complex, Histone Deacetylase 1, Microtubule-Associated Proteins, Neurons, Rats, Sprague-Dawley, Receptor, Nerve Growth Factor
Show Abstract · Added March 27, 2019
During development, neurons undergo apoptosis if they do not receive adequate trophic support from tissues they innervate or when detrimental factors activate the p75 neurotrophin receptor (p75NTR) at their axon ends. Trophic factor deprivation (TFD) or activation of p75NTR in distal axons results in a retrograde degenerative signal. However, the nature of this signal and the regulation of its transport are poorly understood. Here, we identify p75NTR intracellular domain (ICD) and histone deacetylase 1 (HDAC1) as part of a retrograde pro-apoptotic signal generated in response to TFD or ligand binding to p75NTR in sympathetic neurons. We report an unconventional function of HDAC1 in retrograde transport of a degenerative signal and its constitutive presence in sympathetic axons. HDAC1 deacetylates dynactin subunit p150, which enhances its interaction with dynein. These findings define p75NTR ICD as a retrograde degenerative signal and reveal p150 deacetylation as a unique mechanism regulating axonal transport.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
2 Members
0 Resources
MeSH Terms
Striking parallels between carotid body glomus cell and adrenal chromaffin cell development.
Hockman D, Adameyko I, Kaucka M, Barraud P, Otani T, Hunt A, Hartwig AC, Sock E, Waithe D, Franck MCM, Ernfors P, Ehinger S, Howard MJ, Brown N, Reese J, Baker CVH
(2018) Dev Biol 444 Suppl 1: S308-S324
MeSH Terms: Adrenal Glands, Animals, Basic Helix-Loop-Helix Transcription Factors, Body Patterning, Carotid Body, Cell Differentiation, Cell Hypoxia, Chick Embryo, Chickens, Chromaffin Cells, Mice, Mice, Knockout, Myelin Proteolipid Protein, Neural Crest, Neurons, Pericytes, Transcription Factors
Show Abstract · Added May 30, 2018
Carotid body glomus cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific cells for Parkinson's disease therapy. Like adrenal chromaffin cells, which are also hypoxia-sensitive, glomus cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between glomus and adrenal chromaffin cell development. Moreover, histology has long suggested that glomus cell precursors are 'émigrés' from neighbouring ganglia/nerves, while multipotent nerve-associated glial cells are now known to make a significant contribution to the adrenal chromaffin cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to glomus cells. Finally, we resolve a paradox for the 'émigré' hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'émigrés' to the neural crest.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Bergmann glial Sonic hedgehog signaling activity is required for proper cerebellar cortical expansion and architecture.
Cheng FY, Fleming JT, Chiang C
(2018) Dev Biol 440: 152-166
MeSH Terms: Animals, Astrocytes, Cell Differentiation, Cell Division, Cell Proliferation, Cells, Cultured, Cerebellar Cortex, Cerebellar Neoplasms, Cerebellum, Developmental Disabilities, Hedgehog Proteins, Mice, Nervous System Malformations, Neural Stem Cells, Neuroglia, Neurons, Purkinje Cells, Signal Transduction, Wnt Signaling Pathway
Show Abstract · Added April 10, 2019
Neuronal-glial relationships play a critical role in the maintenance of central nervous system architecture and neuronal specification. A deeper understanding of these relationships can elucidate cellular cross-talk capable of sustaining proper development of neural tissues. In the cerebellum, cerebellar granule neuron precursors (CGNPs) proliferate in response to Purkinje neuron-derived Sonic hedgehog (Shh) before ultimately exiting the cell cycle and migrating radially along Bergmann glial fibers. However, the function of Bergmann glia in CGNP proliferation remains not well defined. Interestingly, the Hh pathway is also activated in Bergmann glia, but the role of Shh signaling in these cells is unknown. In this study, we show that specific ablation of Shh signaling using the tamoxifen-inducible TNC line to eliminate Shh pathway activator Smoothened in Bergmann glia is sufficient to cause severe cerebellar hypoplasia and a significant reduction in CGNP proliferation. TNC; Smo (Smo) mice demonstrate an obvious reduction in cerebellar size within two days of ablation of Shh signaling. Mutant cerebella have severely reduced proliferation and increased differentiation of CGNPs due to a significant decrease in Shh activity and concomitant activation of Wnt signaling in Smo CGNPs, suggesting that this pathway is involved in cross-talk with the Shh pathway in regulating CGNP proliferation. In addition, Purkinje cells are ectopically located, their dendrites stunted, and the Bergmann glial network disorganized. Collectively, these data demonstrate a previously unappreciated role for Bergmann glial Shh signaling activity in the proliferation of CGNPs and proper maintenance of cerebellar architecture.
Copyright © 2018 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
Analysis of neuroanatomical differences in mice with genetically modified serotonin transporters assessed by structural magnetic resonance imaging.
Ellegood J, Yee Y, Kerr TM, Muller CL, Blakely RD, Henkelman RM, Veenstra-VanderWeele J, Lerch JP
(2018) Mol Autism 9: 24
MeSH Terms: Animals, Brain, Female, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred C57BL, Mutation, Neurons, Serotonin, Serotonin Plasma Membrane Transport Proteins
Show Abstract · Added May 4, 2018
Background - The serotonin (5-HT) system has long been implicated in autism spectrum disorder (ASD) as indicated by elevated whole blood and platelet 5-HT, altered platelet and brain receptor and transporter binding, and genetic linkage and association findings. Based upon work in genetically modified mice, 5-HT is known to influence several aspects of brain development, but systematic neuroimaging studies have not previously been reported. In particular, the 5-HT transporter (serotonin transporter, SERT; 5-HTT) gene, , has been extensively studied.
Methods - Using a 7-T MRI and deformation-based morphometry, we assessed neuroanatomical differences in an knockout mouse on a C57BL/6 genetic background, along with an Ala56 knockin mouse on two different genetic backgrounds (129S and C57BL/6).
Results - Individually (same sex, same background, same genotype), the only differences found were in the female knockout mouse; all the others had no significant differences. However, an analysis of variance across the whole study sample revealed a significant effect of on the amygdala, thalamus, dorsal raphe nucleus, and lateral and frontal cortices.
Conclusions - This work shows that an increase or decrease in SERT function has a significant effect on the neuroanatomy in 5-HT relevant regions, particularly the raphe nuclei. Notably, the Ala56 knockin alone appears to have an insignificant, but suggestive, effect compared to the KO, which is consistent with function. Despite the small number of 5-HT neurons and their localization to the brainstem, it is clear that 5-HT plays an important role in neuroanatomical organization.
1 Communities
0 Members
0 Resources
11 MeSH Terms
Cholinergic Projections to the Substantia Nigra Pars Reticulata Inhibit Dopamine Modulation of Basal Ganglia through the M Muscarinic Receptor.
Moehle MS, Pancani T, Byun N, Yohn SE, Wilson GH, Dickerson JW, Remke DH, Xiang Z, Niswender CM, Wess J, Jones CK, Lindsley CW, Rook JM, Conn PJ
(2017) Neuron 96: 1358-1372.e4
MeSH Terms: Acetylcholine, Animals, Basal Ganglia, Channelrhodopsins, Choline O-Acetyltransferase, Cholinergic Agents, Cholinergic Neurons, Dopamine, Inhibitory Postsynaptic Potentials, Locomotion, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurotransmitter Agents, Oxygen, Pars Reticulata, Pedunculopontine Tegmental Nucleus, Receptor, Muscarinic M4, Receptors, Dopamine D1, Signal Transduction
Show Abstract · Added March 14, 2018
Cholinergic regulation of dopaminergic inputs into the striatum is critical for normal basal ganglia (BG) function. This regulation of BG function is thought to be primarily mediated by acetylcholine released from cholinergic interneurons (ChIs) acting locally in the striatum. We now report a combination of pharmacological, electrophysiological, optogenetic, chemogenetic, and functional magnetic resonance imaging studies suggesting extra-striatal cholinergic projections from the pedunculopontine nucleus to the substantia nigra pars reticulata (SNr) act on muscarinic acetylcholine receptor subtype 4 (M) to oppose cAMP-dependent dopamine receptor subtype 1 (D) signaling in presynaptic terminals of direct pathway striatal spiny projections neurons. This induces a tonic inhibition of transmission at direct pathway synapses and D-mediated activation of motor activity. These studies provide important new insights into the unique role of M in regulating BG function and challenge the prevailing hypothesis of the centrality of striatal ChIs in opposing dopamine regulation of BG output.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
2 Members
0 Resources
20 MeSH Terms
Neuronal activity drives FMRP- and HSPG-dependent matrix metalloproteinase function required for rapid synaptogenesis.
Dear ML, Shilts J, Broadie K
(2017) Sci Signal 10:
MeSH Terms: Animals, Disease Models, Animal, Drosophila Proteins, Drosophila melanogaster, Fragile X Syndrome, Heparan Sulfate Proteoglycans, Matrix Metalloproteinase 1, Matrix Metalloproteinase 2, Neuromuscular Junction, Neurons, Presynaptic Terminals, Proteoglycans, Wnt Signaling Pathway
Show Abstract · Added December 7, 2017
Matrix metalloproteinase (MMP) functions modulate synapse formation and activity-dependent plasticity. Aberrant MMP activity is implicated in fragile X syndrome (FXS), a disease caused by the loss of the RNA-binding protein FMRP and characterized by neurological dysfunction and intellectual disability. Gene expression studies in suggest that Mmps cooperate with the heparan sulfate proteoglycan (HSPG) glypican co-receptor Dally-like protein (Dlp) to restrict trans-synaptic Wnt signaling and that synaptogenic defects in the fly model of FXS are alleviated by either inhibition of Mmp or genetic reduction of Dlp. We used the neuromuscular junction (NMJ) glutamatergic synapse to test activity-dependent Dlp and Mmp intersections in the context of FXS. We found that rapid, activity-dependent synaptic bouton formation depended on secreted Mmp1. Acute neuronal stimulation reduced the abundance of Mmp2 but increased that of both Mmp1 and Dlp, as well as enhanced the colocalization of Dlp and Mmp1 at the synapse. Dlp function promoted Mmp1 abundance, localization, and proteolytic activity around synapses. Dlp glycosaminoglycan (GAG) chains mediated this functional interaction with Mmp1. In the FXS fly model, activity-dependent increases in Mmp1 abundance and activity were lost but were restored by reducing the amount of synaptic Dlp. The data suggest that neuronal activity-induced, HSPG-dependent Mmp regulation drives activity-dependent synaptogenesis and that this is impaired in FXS. Thus, exploring this mechanism further may reveal therapeutic targets that have the potential to restore synaptogenesis in FXS patients.
Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
1 Communities
0 Members
0 Resources
13 MeSH Terms
A Role for Dystonia-Associated Genes in Spinal GABAergic Interneuron Circuitry.
Zhang J, Weinrich JAP, Russ JB, Comer JD, Bommareddy PK, DiCasoli RJ, Wright CVE, Li Y, van Roessel PJ, Kaltschmidt JA
(2017) Cell Rep 21: 666-678
MeSH Terms: Animals, Biomarkers, Dystonia, GABAergic Neurons, Genetic Predisposition to Disease, Interneurons, Male, Mice, Mutant Strains, Molecular Chaperones, Mutation, Nerve Net, Presynaptic Terminals, Proprioception, Spinal Cord, Transcription Factors
Show Abstract · Added November 7, 2017
Spinal interneurons are critical modulators of motor circuit function. In the dorsal spinal cord, a set of interneurons called GABApre presynaptically inhibits proprioceptive sensory afferent terminals, thus negatively regulating sensory-motor signaling. Although deficits in presynaptic inhibition have been inferred in human motor diseases, including dystonia, it remains unclear whether GABApre circuit components are altered in these conditions. Here, we use developmental timing to show that GABApre neurons are a late Ptf1a-expressing subclass and localize to the intermediate spinal cord. Using a microarray screen to identify genes expressed in this intermediate population, we find the kelch-like family member Klhl14, implicated in dystonia through its direct binding with torsion-dystonia-related protein Tor1a. Furthermore, in Tor1a mutant mice in which Klhl14 and Tor1a binding is disrupted, formation of GABApre sensory afferent synapses is impaired. Our findings suggest a potential contribution of GABApre neurons to the deficits in presynaptic inhibition observed in dystonia.
Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
2 Communities
1 Members
0 Resources
15 MeSH Terms
Sympathetic neuron-associated macrophages contribute to obesity by importing and metabolizing norepinephrine.
Pirzgalska RM, Seixas E, Seidman JS, Link VM, Sánchez NM, Mahú I, Mendes R, Gres V, Kubasova N, Morris I, Arús BA, Larabee CM, Vasques M, Tortosa F, Sousa AL, Anandan S, Tranfield E, Hahn MK, Iannacone M, Spann NJ, Glass CK, Domingos AI
(2017) Nat Med 23: 1309-1318
MeSH Terms: Animals, CX3C Chemokine Receptor 1, Gene Expression Profiling, Homeostasis, Macrophages, Mice, Mice, Inbred C57BL, Mice, Transgenic, Neurons, Norepinephrine, Norepinephrine Plasma Membrane Transport Proteins, Obesity, Sympathetic Nervous System
Show Abstract · Added February 9, 2018
The cellular mechanism(s) linking macrophages to norepinephrine (NE)-mediated regulation of thermogenesis have been a topic of debate. Here we identify sympathetic neuron-associated macrophages (SAMs) as a population of cells that mediate clearance of NE via expression of solute carrier family 6 member 2 (SLC6A2), an NE transporter, and monoamine oxidase A (MAOA), a degradation enzyme. Optogenetic activation of the sympathetic nervous system (SNS) upregulates NE uptake by SAMs and shifts the SAM profile to a more proinflammatory state. NE uptake by SAMs is prevented by genetic deletion of Slc6a2 or inhibition of the encoded transporter. We also observed an increased proportion of SAMs in the SNS of two mouse models of obesity. Genetic ablation of Slc6a2 in SAMs increases brown adipose tissue (BAT) content, causes browning of white fat, increases thermogenesis, and leads to substantial and sustained weight loss in obese mice. We further show that this pathway is conserved, as human sympathetic ganglia also contain SAMs expressing the analogous molecular machinery for NE clearance, which thus constitutes a potential target for obesity treatment.
1 Communities
0 Members
0 Resources
13 MeSH Terms
Lkb1 regulates granule cell migration and cortical folding of the cerebellar cortex.
Ryan KE, Kim PS, Fleming JT, Brignola E, Cheng FY, Litingtung Y, Chiang C
(2017) Dev Biol 432: 165-177
MeSH Terms: Animals, Cell Differentiation, Cell Division, Cell Movement, Cerebellar Cortex, Cytoplasmic Granules, Hedgehog Proteins, Mice, Nerve Tissue Proteins, Neurons, Organogenesis, Protein-Serine-Threonine Kinases, Signal Transduction
Show Abstract · Added April 10, 2019
Cerebellar growth and foliation require the Hedgehog-driven proliferation of granule cell precursors (GCPs) in the external granule layer (EGL). However, that increased or extended GCP proliferation generally does not elicit ectopic folds suggests that additional determinants control cortical expansion and foliation during cerebellar development. Here, we find that genetic loss of the serine-threonine kinase Liver Kinase B1 (Lkb1) in GCPs increased cerebellar cortical size and foliation independent of changes in proliferation or Hedgehog signaling. This finding is unexpected given that Lkb1 has previously shown to be critical for Hedgehog pathway activation in cultured cells. Consistent with unchanged proliferation rate of GCPs, the cortical expansion of Lkb1 mutants is accompanied by thinning of the EGL. The plane of cell division, which has been implicated in diverse processes from epithelial surface expansions to gyrification of the human cortex, remains unchanged in the mutants when compared to wild-type controls. However, we find that Lkb1 mutants display delayed radial migration of post-mitotic GCPs that coincides with increased cortical size, suggesting that aberrant cell migration may contribute to the cortical expansion and increase foliation. Taken together, our results reveal an important role for Lkb1 in regulating cerebellar cortical size and foliation in a Hedgehog-independent manner.
Copyright © 2017 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
MeSH Terms
From the Cover: Manganese and Rotenone-Induced Oxidative Stress Signatures Differ in iPSC-Derived Human Dopamine Neurons.
Neely MD, Davison CA, Aschner M, Bowman AB
(2017) Toxicol Sci 159: 366-379
MeSH Terms: Cell Differentiation, Cells, Cultured, Dopaminergic Neurons, Humans, Induced Pluripotent Stem Cells, Lipid Peroxidation, Manganese, Oxidative Stress, Reactive Nitrogen Species, Reactive Oxygen Species, Rotenone
Show Abstract · Added April 11, 2018
Parkinson's disease (PD) is the result of complex interactions between genetic and environmental factors. Two chemically distinct environmental stressors relevant to PD are the metal manganese and the pesticide rotenone. Both are thought to exert neurotoxicity at least in part via oxidative stress resulting from impaired mitochondrial activity. Identifying shared mechanism of action may reveal clues towards an understanding of the mechanisms underlying PD pathogenesis. Here we compare the effects of manganese and rotenone in human-induced pluripotent stem cells-derived postmitotic mesencephalic dopamine neurons by assessing several different oxidative stress endpoints. Manganese, but not rotenone caused a concentration and time-dependent increase in intracellular reactive oxygen/nitrogen species measured by quantifying the fluorescence of oxidized chloromethyl 2',7'-dichlorodihydrofluorescein diacetate (DCF) assay. In contrast, rotenone but not manganese caused an increase in cellular isoprostane levels, an indicator of lipid peroxidation. Manganese and rotenone both caused an initial decrease in cellular reduced glutathione; however, glutathione levels remained low in neurons treated with rotenone for 24 h but recovered in manganese-exposed cells. Neurite length, a sensitive indicator of overall neuronal health was adversely affected by rotenone, but not manganese. Thus, our observations suggest that the cellular oxidative stress evoked by these 2 agents is distinct yielding unique oxidative stress signatures across outcome measures. The protective effect of rasagiline, a compound used in the clinic for PD, had negligible impact on any of oxidative stress outcome measures except a subtle significant decrease in manganese-dependent production of reactive oxygen/nitrogen species detected by the DCF assay.
© The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
0 Communities
1 Members
0 Resources
11 MeSH Terms