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- Narcolepsy (2)
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- Acetylcholine; arousal; brain slice; hypocretin; oscillations; reticular activating system; serotonin (1)
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- Ca2+ signaling; dorsal raphe nucleus; laterodorsal tegmental nucleus; locus coeruleus; whole-cell patch-clamp recording (1)
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- Cardiac contractility; epoxyeicosatrienoic acids; peroxisome proliferator‐activated receptors; sex; soluble epoxide hydrolase (1)
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Articles 1 - 15 of 15
Full-Text Articles in Physiology
Anti-Human Cd9 Antibody Fab Fragment Impairs The Internalization Of Extracellular Vesicles And The Nuclear Transfer Of Their Cargo Proteins., Mark F. Santos, Germana Rappa, Jana Karbanová, Cheryl Vanier, Chikao Morimoto, Denis Corbeil, Aurelio Lorico
Anti-Human Cd9 Antibody Fab Fragment Impairs The Internalization Of Extracellular Vesicles And The Nuclear Transfer Of Their Cargo Proteins., Mark F. Santos, Germana Rappa, Jana Karbanová, Cheryl Vanier, Chikao Morimoto, Denis Corbeil, Aurelio Lorico
College of Osteopathic Medicine (TUN) Publications and Research
The intercellular communication mediated by extracellular vesicles (EVs) has gained international interest during the last decade. Interfering with the mechanisms regulating this cellular process might find application particularly in oncology where cancer cell-derived EVs play a role in tumour microenvironment transformation. Although several mechanisms were ascribed to explain the internalization of EVs, little is our knowledge about the fate of their cargos, which are crucial to mediate their function. We recently demonstrated a new intracellular pathway in which a fraction of endocytosed EV-associated proteins is transported into the nucleoplasm of the host cell via a subpopulation of late endosomes penetrating …
Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro
Extracellular Vesicles As Biological Shuttles For Targeted Therapies., Stefania Raimondo, Gianluca Giavaresi, Aurelio Lorico, Riccardo Alessandro
College of Osteopathic Medicine (TUN) Publications and Research
The development of effective nanosystems for drug delivery represents a key challenge for the improvement of most current anticancer therapies. Recent progress in the understanding of structure and function of extracellular vesicles (EVs)-specialized membrane-bound nanocarriers for intercellular communication-suggests that they might also serve as optimal delivery systems of therapeutics. In addition to carrying proteins, lipids, DNA and different forms of RNAs, EVs can be engineered to deliver specific bioactive molecules to target cells. Exploitation of their molecular composition and physical properties, together with improvement in bio-techniques to modify their content are critical issues to target them to specific cells/tissues/organs. Here, …
The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar
The Transcriptional Regulation Of The Human Angiotensinogen Gene After High-Fat Diet Is Haplotype-Dependent: Novel Insights Into The Gene-Regulatory Networks And Implications For Human Hypertension, A Rana, S Jain, N Puri, M Kaw, N Sirianni, D Eren, Brahma Mopidevi, Anand Kumar
NYMC Faculty Publications
Single nucleotide polymorphisms (SNPs) in the human angiotensinogen (hAGT) gene may modulate its transcription and affect the regulation of blood pressure via activation of the renin-angiotensin aldosterone system (RAAS). In this regard, we have identified polymorphisms in the 2.5 Kb promoter of the hAGT gene that form two haplotype (Hap) blocks: -6A/G (-1670A/G, -1562C/T, -1561T/C) and -217A/G (-532T/C, -793A/G, -1074T/C & -1178G/A). hAGT gene with Hap -6A/-217A (Hap I) is associated with increased blood pressure whereas, Hap -6G/-217G (Hap II) is associated with normal blood pressure in human subjects. Since RAAS over activity contributes to hypertension in obesity, we have …
Phenotypically Heterogeneous Podoplanin-Expressing Cell Populations Are Associated With The Lymphatic Vessel Growth And Fibrogenic Responses In The Acutely And Chronically Infarcted Myocardium, M Cimini, A Cannata, G Pasquinelli, Marcello Rota, P Goichberg
Phenotypically Heterogeneous Podoplanin-Expressing Cell Populations Are Associated With The Lymphatic Vessel Growth And Fibrogenic Responses In The Acutely And Chronically Infarcted Myocardium, M Cimini, A Cannata, G Pasquinelli, Marcello Rota, P Goichberg
NYMC Faculty Publications
Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of …
Dental Topography And Microwear Texture In Sapajus Apella, Peter S. Ungar, Claire L. Hartgrove, Alexa N. Wimberly, Mark F. Teaford
Dental Topography And Microwear Texture In Sapajus Apella, Peter S. Ungar, Claire L. Hartgrove, Alexa N. Wimberly, Mark F. Teaford
Faculty Publications & Research of the TUC College of Osteopathic Medicine
Dental microwear texture pattern has been associated with aspects of diet for a broad range of mammalian taxa. The basic idea is that soft, tough foods are sheared with a steeper angle of approach between opposing occlusal surfaces, whereas hard, brittle items are crushed with forces perpendicular to those surfaces; and this difference is manifested in anisotropic, striated microwear textures for tough foods, and complex, pitted ones for hard objects. Other factors may, however, influence microwear texture pattern and confound diet signals. For example, if tooth surface slope influences angle of approach between opposing teeth, then perhaps wear-related changes in …
Dental Biotribology: Final Thoughts And Future Directions, Zhongrong Zhou, Paul Constantino, Mark Hoffman, Mugino Kubo, Gildas Merceron, Mark Purnell, Mark F. Teaford
Dental Biotribology: Final Thoughts And Future Directions, Zhongrong Zhou, Paul Constantino, Mark Hoffman, Mugino Kubo, Gildas Merceron, Mark Purnell, Mark F. Teaford
Faculty Publications & Research of the TUC College of Osteopathic Medicine
No abstract provided.
In Vivo Rates Of Dental Microwear Formation In Laboratory Primates Fed Different Food Items, Mark F. Teaford, Peter S. Ungar, Andrea B. Taylor, Callum F. Ross, Christopher J. Vinyard
In Vivo Rates Of Dental Microwear Formation In Laboratory Primates Fed Different Food Items, Mark F. Teaford, Peter S. Ungar, Andrea B. Taylor, Callum F. Ross, Christopher J. Vinyard
Faculty Publications & Research of the TUC College of Osteopathic Medicine
No abstract provided.
Hypocretin/Orexin Peptides Alter Spike Encoding By Serotonergic Dorsal Raphe Neurons Through Two Distinct Mechanisms That Increase The Late Afterhyperpolarization, Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N. Ross, Christopher S. Leonard
Hypocretin/Orexin Peptides Alter Spike Encoding By Serotonergic Dorsal Raphe Neurons Through Two Distinct Mechanisms That Increase The Late Afterhyperpolarization, Masaru Ishibashi, Iryna Gumenchuk, Kenichi Miyazaki, Takafumi Inoue, William N. Ross, Christopher S. Leonard
NYMC Faculty Publications
Orexins (hypocretins) are neuropeptides that regulate multiple homeostatic processes, including reward and arousal, in part by exciting serotonergic dorsal raphe neurons, the major source of forebrain serotonin. Here, using mouse brain slices, we found that, instead of simply depolarizing these neurons, orexin-A altered the spike encoding process by increasing the postspike afterhyperpolarization (AHP) via two distinct mechanisms. This orexin-enhanced AHP (oeAHP) was mediated by both OX1 and OX2 receptors, required Ca(2+) influx, reversed near EK, and decayed with two components, the faster of which resulted from enhanced SK channel activation, whereas the slower component decayed like a slow AHP (sAHP), …
Sexually Dimorphic Adaptation Of Cardiac Function: Roles Of Epoxyeicosatrienoic Acid And Peroxisome Proliferator-Activated Receptors, Jun Qin, Yicong Le, Ghezal Froogh, Sharath Kandhi, Houli Jiang, Dong Sun, An Huang
Sexually Dimorphic Adaptation Of Cardiac Function: Roles Of Epoxyeicosatrienoic Acid And Peroxisome Proliferator-Activated Receptors, Jun Qin, Yicong Le, Ghezal Froogh, Sharath Kandhi, Houli Jiang, Dong Sun, An Huang
NYMC Faculty Publications
Epoxyeicosatrienoic acids (EETs) are cardioprotective mediators metabolized by soluble epoxide hydrolase (sEH) to form corresponding diols (DHETs). As a sex-susceptible target, sEH is involved in the sexually dimorphic regulation of cardiovascular function. Thus, we hypothesized that the female sex favors EET-mediated potentiation of cardiac function via downregulation of sEH expression, followed by upregulation of peroxisome proliferator-activated receptors (PPARs). Hearts were isolated from male (M) and female (F) wild-type (WT) and sEH-KO mice, and perfused with constant flow at different preloads. Basal coronary flow required to maintain the perfusion pressure at 100 mmHg was significantly greater in females than males, and …
Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard
Orexin Receptor Activation Generates Gamma Band Input To Cholinergic And Serotonergic Arousal System Neurons And Drives An Intrinsic Ca(2+)-Dependent Resonance In Ldt And Ppt Cholinergic Neurons, Masaru Ishibashi, Iryna Gumenchuk, Bryan Kang, Catherine Steger, Elizabeth Lynn, Nancy Molina, Leonard M. Eisenberg, Christopher S. Leonard
NYMC Faculty Publications
A hallmark of the waking state is a shift in EEG power to higher frequencies with epochs of synchronized intracortical gamma activity (30-60 Hz) - a process associated with high-level cognitive functions. The ascending arousal system, including cholinergic laterodorsal (LDT) and pedunculopontine (PPT) tegmental neurons and serotonergic dorsal raphe (DR) neurons, promotes this state. Recently, this system has been proposed as a gamma wave generator, in part, because some neurons produce high-threshold, Ca(2+)-dependent oscillations at gamma frequencies. However, it is not known whether arousal-related inputs to these neurons generate such oscillations, or whether such oscillations are ever transmitted to neuronal …
Differential Actions Of Orexin Receptors In Brainstem Cholinergic And Monoaminergic Neurons Revealed By Receptor Knockouts: Implications For Orexinergic Signaling In Arousal And Narcolepsy, Kristi Kohlmeier, Christopher Tyler, Mike Kalogiannis, Masaru Ishibashi, Iryna Gumenchuk, Masashi Yanagisawa, Christopher S. Leonard
Differential Actions Of Orexin Receptors In Brainstem Cholinergic And Monoaminergic Neurons Revealed By Receptor Knockouts: Implications For Orexinergic Signaling In Arousal And Narcolepsy, Kristi Kohlmeier, Christopher Tyler, Mike Kalogiannis, Masaru Ishibashi, Iryna Gumenchuk, Masashi Yanagisawa, Christopher S. Leonard
NYMC Faculty Publications
Orexin neuropeptides influence multiple homeostatic functions and play an essential role in the expression of normal sleep-wake behavior. While their two known receptors (OX1 and OX2) are targets for novel pharmacotherapeutics, the actions mediated by each receptor remain largely unexplored. Using brain slices from mice constitutively lacking either receptor, we used whole-cell and Ca(2+) imaging methods to delineate the cellular actions of each receptor within cholinergic [laterodorsal tegmental nucleus (LDT)] and monoaminergic [dorsal raphe (DR) and locus coeruleus (LC)] brainstem nuclei-where orexins promote arousal and suppress REM sleep. In slices from OX(-/-) 2 mice, orexin-A (300 nM) elicited wild-type responses …
Cholinergic Modulation Of Narcoleptic Attacks In Double Orexin Receptor Knockout Mice, Mike Kalogiannis, Emily Hsu, Jon Willie, Richard Chemelli, Yaz Kisanuki, Masashi Yanagisawa, Christopher S. Leonard
Cholinergic Modulation Of Narcoleptic Attacks In Double Orexin Receptor Knockout Mice, Mike Kalogiannis, Emily Hsu, Jon Willie, Richard Chemelli, Yaz Kisanuki, Masashi Yanagisawa, Christopher S. Leonard
NYMC Faculty Publications
To investigate how cholinergic systems regulate aspects of the sleep disorder narcolepsy, we video-monitored mice lacking both orexin (hypocretin) receptors (double knockout; DKO mice) while pharmacologically altering cholinergic transmission. Spontaneous behavioral arrests in DKO mice were highly similar to those reported in orexin-deficient mice and were never observed in wild-type (WT) mice. A survival analysis revealed that arrest lifetimes were exponentially distributed indicating that random, Markovian processes determine arrest lifetime. Low doses (0.01, 0.03 mg/kg, i.p.), but not a high dose (0.08 mg/kg, i.p.) of the cholinesterase inhibitor physostigmine increased the number of arrests but did not alter arrest lifetimes. …
Specific Functions Of Synaptically Localized Potassium Channels In Synaptic Transmission At The Neocortical Gabaergic Fast-Spiking Cell Synapse, Ethan Goldberg, Shigeo Watanabe, Su Ying Chang, Rolf Joho, Z Josh Huang, Christopher S. Leonard, Bernardo Rudy
Specific Functions Of Synaptically Localized Potassium Channels In Synaptic Transmission At The Neocortical Gabaergic Fast-Spiking Cell Synapse, Ethan Goldberg, Shigeo Watanabe, Su Ying Chang, Rolf Joho, Z Josh Huang, Christopher S. Leonard, Bernardo Rudy
NYMC Faculty Publications
Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 channels the ability to accelerate the repolarization of the action potential (AP) efficiently and specifically. In the cortex, the Kv3.1 and Kv3.2 proteins are expressed prominently in a subset of GABAergic interneurons known as fast-spiking (FS) cells and in fact are a significant determinant of the fast-spiking discharge pattern. However, in addition to expression at FS cell somata, Kv3.1 and Kv3.2 proteins also are expressed prominently at …
Direct And Indirect Excitation Of Laterodorsal Tegmental Neurons By Hypocretin/Orexin Peptides: Implications For Wakefulness And Narcolepsy, Sophie Burlet, Christopher Tyler, Christopher S. Leonard
Direct And Indirect Excitation Of Laterodorsal Tegmental Neurons By Hypocretin/Orexin Peptides: Implications For Wakefulness And Narcolepsy, Sophie Burlet, Christopher Tyler, Christopher S. Leonard
NYMC Faculty Publications
Compelling evidence links the recently discovered hypothalamic peptides Hypocretin/Orexin (Hcrt/Orx) to rapid eye movement sleep (REM) control and the sleep disorder narcolepsy, yet how they influence sleep-related systems is not well understood. We investigated the action of Hcrt/Orx on mesopontine cholinergic (MPCh) neurons of the laterodorsal tegmental nucleus (LDT), a target group whose function is altered in canine narcolepsy and appears pivotal for normal REM and wakefulness. Extracellular recordings from mouse brainstem slices revealed that Hcrt/Orx evoked prolonged firing of LDT neurons. Whole-cell recordings revealed that Hcrt/Orx had actions on both presynaptic neurons and at postsynaptic sites. Hcrt/Orx produced an …
Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy
Impaired Fast-Spiking, Suppressed Cortical Inhibition, And Increased Susceptibility To Seizures In Mice Lacking Kv3.2 K+ Channel Proteins, David Lau, Eleazar Vega-Saenz De Miera, Diego Contreras, Alan Chow, Richard Paylor, Christopher S. Leonard, Bernardo Rudy
NYMC Faculty Publications
Voltage-gated K(+) channels of the Kv3 subfamily have unusual electrophysiological properties, including activation at very depolarized voltages (positive to -10 mV) and very fast deactivation rates, suggesting special roles in neuronal excitability. In the brain, Kv3 channels are prominently expressed in select neuronal populations, which include fast-spiking (FS) GABAergic interneurons of the neocortex, hippocampus, and caudate, as well as other high-frequency firing neurons. Although evidence points to a key role in high-frequency firing, a definitive understanding of the function of these channels has been hampered by a lack of selective pharmacological tools. We therefore generated mouse lines in which one …