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Articles 31 - 40 of 40
Full-Text Articles in Neurosciences
Ampk Modulation Ameliorates Dominant Disease Phenotypes Of Ctrp5 Variant In Retinal Degeneration, Kiyoharu J. Miyagishima, Ruchi Sharma, Malika Nimmagadda, Katharina Clore-Gronenborn, Zoya Qureshy, Davide Ortolan, Devika Bose, Mitra Farnoodian, Congxiao Zhang, Andrew Fausey, Yuri V. Sergeev, Mones Abu-Asab, Bokkyoo Jun, Khanh V. Do, Marie Audrey Kautzman Guerin, Jorgelina Calandria, Aman George, Bin Guan, Qin Wan, Rachel C. Sharp
Ampk Modulation Ameliorates Dominant Disease Phenotypes Of Ctrp5 Variant In Retinal Degeneration, Kiyoharu J. Miyagishima, Ruchi Sharma, Malika Nimmagadda, Katharina Clore-Gronenborn, Zoya Qureshy, Davide Ortolan, Devika Bose, Mitra Farnoodian, Congxiao Zhang, Andrew Fausey, Yuri V. Sergeev, Mones Abu-Asab, Bokkyoo Jun, Khanh V. Do, Marie Audrey Kautzman Guerin, Jorgelina Calandria, Aman George, Bin Guan, Qin Wan, Rachel C. Sharp
School of Graduate Studies Faculty Publications
Late-onset retinal degeneration (L-ORD) is an autosomal dominant disorder caused by a missense substitution in CTRP5. Distinctive clinical features include sub-retinal pigment epithelium (RPE) deposits, choroidal neovascularization, and RPE atrophy. In induced pluripotent stem cells-derived RPE from L-ORD patients (L-ORD-iRPE), we show that the dominant pathogenic CTRP5 variant leads to reduced CTRP5 secretion. In silico modeling suggests lower binding of mutant CTRP5 to adiponectin receptor 1 (ADIPOR1). Downstream of ADIPOR1 sustained activation of AMPK renders it insensitive to changes in AMP/ATP ratio resulting in defective lipid metabolism, reduced Neuroprotectin D1(NPD1) secretion, lower mitochondrial respiration, and reduced ATP production. These metabolic …
Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian
Enhancing Mask Activity In Dopaminergic Neurons Extends Lifespan In Flies, Xiaolin Tian
School of Medicine Faculty Publications
Dopaminergic neurons (DANs) are essential modulators for brain functions involving memory formation, reward processing, and decision-making. Here I demonstrate a novel and important function of the DANs in regulating aging and longevity. Overexpressing the putative scaffolding protein Mask in two small groups of DANs in flies can significantly extend the lifespan in flies and sustain adult locomotor and fecundity at old ages. This Mask-induced beneficial effect requires dopaminergic transmission but cannot be recapitulated by elevating dopamine production alone in the DANs. Independent activation of Gαs in the same two groups of DANs via the drug-inducible DREADD system also extends fly …
Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
Elucidating The Structure And Functions Of Resolvin D6 Isomers On Nerve Regeneration With A Distinctive Trigeminal Transcriptome, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Robert Nshimiyimana, Nicos A. Petasis, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
School of Medicine Faculty Publications
Innervation sustains cornea integrity. Pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) regenerated damaged nerves by stimulating the synthesis of a new stereoisomer of Resolvin D6 (RvD6si). Here, we resolved the structure of this lipid isolated from mouse tears after injured corneas were treated with PEDF + DHA. RvD6si synthesis was inhibited by fluvoxamine, a cytochrome P450 inhibitor, but not by 15- or 5-LOX inhibitors, suggesting that the 4- and 17-hydroxy of DHA have an RR- or SR-configuration. The two compounds were chemically synthesized. Using chiral phase HPLC, four peaks of RvD6si1-4 from tears were resolved. The RR-RvD6 standard eluted …
Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior In Genetically-Selected Marchigian Sardinian (Msp) Rats, Valentina Vozella, Bryan Cruz, Luis A. Natividad, Federica Benvenuti, Nazzareno Cannella, Scott Edwards, Eric P. Zorrilla, Roberto Ciccocioppo, Marisa Roberto
Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior In Genetically-Selected Marchigian Sardinian (Msp) Rats, Valentina Vozella, Bryan Cruz, Luis A. Natividad, Federica Benvenuti, Nazzareno Cannella, Scott Edwards, Eric P. Zorrilla, Roberto Ciccocioppo, Marisa Roberto
School of Graduate Studies Faculty Publications
Marchigian Sardinian alcohol-preferring (msP) rats serve as a unique model of heightened alcohol preference and anxiety disorders. Their innate enhanced stress and poor stress-coping strategies are driven by a genetic polymorphism of the corticotropin-releasing factor receptor 1 (CRF1) in brain areas involved in glucocorticoid signaling. The activation of glucocorticoid receptors (GRs) regulates the stress response, making GRs a candidate target to treat stress and anxiety. Here, we examined whether mifepristone, a GR antagonist known to reduce alcohol drinking in dependent rats, decreases innate symptoms of anxiety in msPs. Male and female msPs were compared to non-selected Wistar counterparts across three …
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
Bioavailability And Spatial Distribution Of Fatty Acids In The Rat Retina After Dietary Omega-3 Supplementation, Elisa Vidal, Bokkyoo Jun, William C. Gordon, Marie Annick Maire, Lucy Martine, Stéphane Grégoire, Spiro Khoury, Stephanie Cabaret, Olivier Berdeaux, Niyazi Acar, Lionel Bretillon, Nicolas G. Bazan
School of Medicine Faculty Publications
Spatial changes of FAs in the retina in response to different dietary n-3 formulations have never been explored, although a diet rich in EPA and DHA is recommended to protect the retina against the effects of aging. In this study, Wistar rats were fed for 8 weeks with balanced diet including either EPA-containing phospholipids (PLs), EPA-containing TGs, DHA-containing PLs, or DHA-containing TGs. Qualitative changes in FA composition of plasma, erythrocytes, and retina were evaluated by gas chromatography-flame ionization detector. Following the different dietary intakes, changes to the quantity and spatial organization of PC and PE species in retina were determined …
Folic Acid Supplementation In Patients With Elevated Homocysteine Levels, Alan D. Kaye, George M. Jeha, Alex D. Pham, Mitchell C. Fuller, Zachary I. Lerner, Gerald T. Sibley, Elyse M. Cornett, Ivan Urits, Omar Viswanath, Christopher G. Kevil
Folic Acid Supplementation In Patients With Elevated Homocysteine Levels, Alan D. Kaye, George M. Jeha, Alex D. Pham, Mitchell C. Fuller, Zachary I. Lerner, Gerald T. Sibley, Elyse M. Cornett, Ivan Urits, Omar Viswanath, Christopher G. Kevil
School of Medicine Faculty Publications
Introduction: Folic acid is the most important dietary determinant of homocysteine (Hcy). Hcy serves as a critical intermediate in methylation reactions. It is created from methionine and either converted back to methionine or transformed into cysteine. This process is aided through several enzymes and three vitamins, folic acid, B12, and B6. Daily supplementation with 0.5–5.0 mg of folic acid typically lowers plasma Hcy levels by approximately 25%. Hyperhomocysteinemia is a known risk factor for coronary artery disease. In this regard, elevated levels of Hcy have been found in a majority of patients with vascular disease. Methods: A literature review of …
Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
Novel Rvd6 Stereoisomer Induces Corneal Nerve Regeneration And Wound Healing Post-Injury By Modulating Trigeminal Transcriptomic Signature, Thang L. Pham, Azucena H. Kakazu, Jiucheng He, Bokkyoo Jun, Nicolas G. Bazan, Haydee E.P. Bazan
School of Medicine Faculty Publications
The high-density corneal innervation plays a pivotal role in sustaining the integrity of the ocular surface. We have previously demonstrated that pigment epithelium-derived factor (PEDF) plus docosahexaenoic acid (DHA) promotes corneal nerve regeneration; here, we report the mechanism involved and the discovery of a stereospecific Resolvin D6-isomer (RvD6si) that drives the process. RvD6si promotes corneal wound healing and functional recovery by restoring corneal innervation after injury. RvD6si applied to the eye surface elicits a specific transcriptome signature in the trigeminal ganglion (TG) that includes Rictor, the rapamycin-insensitive complex-2 of mTOR (mTORC2), and genes involved in axon growth, whereas genes related …
Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta
Radiofrequency Renal Denervation Attenuates Kidney Fibrosis In Spontaneously Hypertensive Rats (2267), Juan Gao, Ian Bart Denys, Luis Del Valle, Mihran V. Naljayan, Daniel R. Kapusta
School of Medicine Faculty Publications
No abstract provided.
Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
Glia-To-Neuron Transfer Of Mirnas Via Extracellular Vesicles: A New Mechanism Underlying Inflammation-Induced Synaptic Alterations, Ilaria Prada, Martina Gabrielli, Elena Turola, Alessia Iorio, Giulia D'Arrigo, Roberta Parolisi, Mariacristina De Luca, Marco Pacifici, Mattia Bastoni, Marta Lombardi, Giuseppe Legname, Dan Cojoc, Annalisa Buffo, Roberto Furlan, Francesca Peruzzi, Claudia Verderio
School of Medicine Faculty Publications
Recent evidence indicates synaptic dysfunction as an early mechanism affected in neuroinflammatory diseases, such as multiple sclerosis, which are characterized by chronic microglia activation. However, the mode(s) of action of reactive microglia in causing synaptic defects are not fully understood. In this study, we show that inflammatory microglia produce extracellular vesicles (EVs) which are enriched in a set of miRNAs that regulate the expression of key synaptic proteins. Among them, miR-146a-5p, a microglia-specific miRNA not present in hippocampal neurons, controls the expression of presynaptic synaptotagmin1 (Syt1) and postsynaptic neuroligin1 (Nlg1), an adhesion protein which play a crucial role in dendritic …
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi
Hiv-1-Tat Protein Inhibits Sc35-Mediated Tau Exon 10 Inclusion Through Up-Regulation Of Dyrk1a Kinase, Ferdous Kadri, Marco Pacifici, Anna Wilk, Amanda Parker-Struckhoff, Luis Del Valle, Kurt F. Hauser, Pamela E. Knapp, Christopher Parsons, Duane Jeansonne, Adam Lassak, Francesca Peruzzi
School of Medicine Faculty Publications
The HIV-1 transactivator protein Tat is implicated in the neuronal damage that contributes to neurocognitive impairment affecting people living with HIV/AIDS. Aberrant splicing of TAU exon 10 results in tauopathies characterized by alterations in the proportion of TAU isoforms containing three (3R) or four (4R) microtubule-binding repeats. The splicing factor SC35/SRSF2 binds to nuclear RNA and facilitates the incorporation of exon 10 in the TAU molecule. Here, we utilized clinical samples, an animal model, and neuronal cell cultures and found that Tat promotes TAU 3R up-regulation through increased levels of phosphorylated SC35, which is retained in nuclear speckles. This mechanism …