scholarly journals Bladder urothelium converts bacterial lipopolysaccharide information into neural signaling via an ATP-mediated pathway to enhance the micturition reflex for rapid defense

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Norichika Ueda ◽  
Makoto Kondo ◽  
Kentaro Takezawa ◽  
Hiroshi Kiuchi ◽  
Yosuke Sekii ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Rapid Onset ◽  
Bacterial Lipopolysaccharide ◽  
Sensory Receptor ◽  
Urinary Frequency ◽  
Micturition Reflex ◽  
Neural Interaction ◽  
Bladder Urothelium ◽  
Neural Signaling ◽  
Defensive Mechanism

AbstractWhen bacteria enter the bladder lumen, a first-stage active defensive mechanism flushes them out. Although urinary frequency induced by bacterial cystitis is a well-known defensive response against bacteria, the underlying mechanism remains unclear. In this study, using a mouse model of acute bacterial cystitis, we demonstrate that the bladder urothelium senses luminal extracellular bacterial lipopolysaccharide (LPS) through Toll-like receptor 4 and releases the transmitter ATP. Moreover, analysis of purinergic P2X2 and P2X3 receptor-deficient mice indicated that ATP signaling plays a pivotal role in the LPS-induced activation of L6–S1 spinal neurons through the bladder afferent pathway, resulting in rapid onset of the enhanced micturition reflex. Thus, we revealed a novel defensive mechanism against bacterial infection via an epithelial-neural interaction that induces urinary frequency prior to bacterial clearance by neutrophils of the innate immune system. Our results indicate an important defense role for the bladder urothelium as a chemical-neural transducer, converting bacterial LPS information into neural signaling via an ATP-mediated pathway, with bladder urothelial cells acting as sensory receptor cells.

scholarly journals Rapid-Acting Antidepressant Therapies

2018 ◽  
Author(s):  
Bashkim Kadriu ◽  
Subha Subramanian ◽  
Zhi-De Deng ◽  
Ioline D. Henter ◽  
Lawrence T. Park ◽  
...  
Keyword(s):  
Rapid Onset ◽  
Emergency Setting ◽  
Glutamatergic System ◽  
Major Depressive ◽  
Signaling Systems ◽  
Antidepressant Effects ◽  
Remission Rates ◽  
Electrophysiological Studies ◽  
Antidepressant Efficacy ◽  
Neural Signaling

Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system—such as ketamine—offer rapid antidepressant effects as well as high remission rates, making them attractive therapeutic options. This chapter reviews the evidence for the antidepressant efficacy of several novel therapeutics, including ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine, as well as interventional techniques such as sleep deprivation. Notably, ketamine and esketamine also rapidly reduce suicidal thoughts, making them attractive solutions in an emergency setting. Because studying the rapid onset of antidepressant effects associated with these agents has also improved our understanding of the neurocircuitry and neural signaling systems underlying MDD, some pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed.

Excretion in the Blood-Sucking Bug, Rhodnius Prolixus Ståal

1964 ◽  
Vol 41 (1) ◽  
pp. 163-176 ◽  
Author(s):  
S. H. P. MADDRELL
Keyword(s):  
Underlying Mechanism ◽  
Rapid Onset ◽  
Rhodnius Prolixus ◽  
Malpighian Tubules ◽  
Maximum Response ◽  
Diuretic Hormone ◽  
Blood Sucking ◽  
Constant Rate

1. The course of diuresis in Rhodnius is described and interpreted in terms of the underlying mechanism. 2. The rapid onset of diuresis is attributable to the prompt release of the diuretic hormone into the haemolymph and to an acceleration of the circulation of the haemolymph caused by peristaltic movements of the mid-gut. 3. Diuresis proceeds at a surprisingly constant rate. This is shown to be a reflexion of the fact that the concentration of the diuretic hormone in the haemolymph at this time is always higher than that which causes the maximum response by the Malpighian tubules. 4. The diuretic hormone is quickly destroyed by the activity of the Malpighian tubules and possibly other tissues. Consequently, the extent of diuresis is controlled by the length of time during which diuretic hormone is released into the haemolymph. 5. Excretion is very sensitive to changes in temperature; both the rate of excretion and the composition of the urine are affected.

scholarly journals PD19-08 BLADDER UROTHELIUM TRIGGERS AN IMMEDIATE DEFENSIVE RESPONSE AGAINST BACTERIAL LIPOPOLYSACCHARIDE VIA ATP SIGNALING

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Norichika Ueda ◽  
Makoto Kondo ◽  
Hiroshi Kiuchi ◽  
Yusuke Inagaki ◽  
Kentaro Takezawa ◽  
...  
Keyword(s):  
Bacterial Lipopolysaccharide ◽  
Defensive Response ◽  
Bladder Urothelium ◽  
Atp Signaling

scholarly journals Chrna5 is essential for a rapid and protected response to optogenetic release of endogenous acetylcholine in prefrontal cortex

2020 ◽  
Author(s):  
Sridevi Venkatesan ◽  
Evelyn K. Lambe
Keyword(s):  
Prefrontal Cortex ◽  
Binding Site ◽  
Nicotinic Acetylcholine Receptors ◽  
Nicotinic Receptor ◽  
Brain Slices ◽  
Pyramidal Cells ◽  
Underlying Mechanism ◽  
Rapid Onset ◽  
Cholinergic Signaling ◽  
Cholinergic Response

AbstractOptimal attention performance requires cholinergic modulation of corticothalamic neurons in the prefrontal cortex. These pyramidal cells express specialized nicotinic acetylcholine receptors containing the α5 subunit encoded by Chrna5. Disruption of this gene impairs attention, but the advantage α5 confers for the detection of endogenous cholinergic signaling is unknown. To ascertain this underlying mechanism, we used optogenetics to stimulate cholinergic afferents in prefrontal cortex brain slices from compound-transgenic wild-type and Chrna5 knockout mice of both sexes. These electrophysiological experiments identify that Chrna5 is critical for the rapid onset of the postsynaptic cholinergic response. Loss of α5 slows cholinergic excitation and delays its peak, and these effects are observed in two different optogenetic mouse lines. Disruption of Chrna5 does not otherwise perturb the magnitude of the response, which remains strongly mediated by nicotinic receptors and tightly controlled by autoinhibition via muscarinic M2 receptors. However, when conditions are altered to promote sustained cholinergic receptor stimulation, it becomes evident that α5 also works to protect nicotinic responses against desensitization. Rescuing Chrna5 disruption thus presents the double challenge of improving the onset of cholinergic signaling without triggering desensitization. Here, we identify that an agonist for the unorthodox α-α nicotinic binding site can allosterically enhance this cholinergic pathway considered vital for attention. Minimal NS9283 treatment restores the rapid onset of the postsynaptic cholinergic response without triggering desensitization. Taken together, this work demonstrates the advantages of speed and resilience that Chrna5 confers on endogenous cholinergic signaling, defining a critical window of interest for cue detection and attentional processing.Significance statementThe α5 nicotinic receptor subunit (Chrna5) is important for attention, but its advantage in detecting endogenous cholinergic signals is unknown. Here, we show that α5 subunits permit rapid cholinergic responses in prefrontal cortex and protect these responses from desensitization. Our findings clarify why Chrna5 is required for optimal attentional performance under demanding conditions. To treat the deficit arising from Chrna5 disruption without triggering desensitization, we enhanced nicotinic receptor affinity using NS9283 stimulation at the unorthodox α-α nicotinic binding site. This approach successfully restored the rapid-onset kinetics of endogenous cholinergic neurotransmission. In summary, we reveal a previously unknown role of Chrna5 as well as an effective approach to compensate for genetic disruption and permit fast cholinergic excitation of prefrontal attention circuits.

scholarly journals Urothelial Calcium-Sensing Receptor Modulates Micturition Function via Mediating Detrusor Activity and Ameliorates Bladder Hyperactivity in Rats

2021 ◽  
Vol 14 (10) ◽  
pp. 960
Author(s):  
Wei-Yi Wu ◽  
Shih-Pin Lee ◽  
Bing-Juin Chiang ◽  
Wei-Yu Lin ◽  
Chiang-Ting Chien
Keyword(s):  
Urinary Bladder ◽  
Bladder Smooth Muscle ◽  
Calcium Sensing Receptor ◽  
Efferent Nerve ◽  
Micturition Reflex ◽  
Bladder Urothelium ◽  
Calcium Sensing ◽  
Urinary Bladder Smooth Muscle ◽  
Bladder Disorders

The urothelium displays mechano- and chemosensory functions via numerous receptors and channels. The calcium-sensing receptor (CaSR) detects extracellular calcium and modulates several physiological functions. Nonetheless, information about the expression and the role of CaSR in lower urinary tract has been absent. We aimed to determine the existence of urothelial CaSR in urinary bladder and its effect on micturition function. We utilized Western blot to confirm the expression of CaSR in bladder and used immunofluorescence to verify the location of the CaSR in the bladder urothelium via colocalization with uroplakin III A. The activation of urothelial CaSR via the CaSR agonist, AC-265347 (AC), decreased urinary bladder smooth muscle (detrusor) activity, whereas its inhibition via the CaSR antagonist, NPS-2143 hydrochloride (NPS), increased detrusor activity in in vitro myography experiments. Cystometry, bladder nerve activities recording, and bladder surface microcirculation detection were conducted to evaluate the effects of the urothelial CaSR via intravesical administrations. Intravesical AC inhibited micturition reflex, bladder afferent and efferent nerve activities, and reversed cystitis-induced bladder hyperactivity. The urothelial CaSR demonstrated a chemosensory function, and modulated micturition reflex via regulating detrusor activity. This study provided further evidence of how the urothelial CaSR mediated micturition and implicated the urothelial CaSR as a potential pharmacotherapeutic target in the intervention of bladder disorders.

Rapid-Acting Antidepressants

Depression ◽  
2019 ◽  
pp. 218-240
Author(s):  
Bashkim Kadriu ◽  
Subha Subramanian ◽  
Zhi-De Deng ◽  
Ioline D. Henter ◽  
Lawrence T. Park ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Rapid Onset ◽  
Emergency Setting ◽  
Novel Therapies ◽  
Signaling Systems ◽  
Antidepressant Effects ◽  
Remission Rates ◽  
Electrophysiological Studies ◽  
Antidepressant Efficacy ◽  
Neural Signaling

Major depressive disorder (MDD) is a highly prevalent and debilitating illness and closely linked to suicide risk. Currently available antidepressants take weeks to work and have low remission rates; indeed, about a third of individuals with MDD fail to fully remit in response to these agents. Novel therapies that target the glutamatergic system, such as ketamine, offer rapid antidepressant effects as well as high remission rates, making them attractive therapeutic options. This chapter reviews the evidence for the antidepressant efficacy of several novel therapeutics (ketamine, esketamine, nitrous oxide, scopolamine, GLYX-13, and buprenorphine) as well as interventional techniques such as sleep deprivation. Notably, ketamine and esketamine also rapidly reduce suicidal thoughts, making them attractive solutions in an emergency setting. Because studying the rapid onset of antidepressant effects associated with these agents has also improved our understanding of the neurocircuitry and neural signaling systems underlying MDD, some pivotal drug trials using rodents, neuroimaging, and electrophysiological studies are also reviewed.

Abstract #549 A Case of Rapid Onset Quadriparesis

2019 ◽  
Vol 25 ◽  
pp. 277-278
Author(s):  
Alberto Franco-Akel ◽  
Janpreet Bhandohal ◽  
Mohammad Saeed ◽  
Devendra Tripathi
Keyword(s):  
Rapid Onset

Face Inversion Effect Emerges Under Critical Configural Discrepancy

2010 ◽  
Vol 69 (3) ◽  
pp. 161-167 ◽  
Author(s):  
Jisien Yang ◽  
Adrian Schwaninger
Keyword(s):  
Face Recognition ◽  
Face Processing ◽  
Underlying Mechanism ◽  
Inversion Effect ◽  
Configural Processing ◽  
Major Contributor ◽  
Face Inversion Effect ◽  
Configural Information ◽  
Face Inversion ◽  
The Face

Configural processing has been considered the major contributor to the face inversion effect (FIE) in face recognition. However, most researchers have only obtained the FIE with one specific ratio of configural alteration. It remains unclear whether the ratio of configural alteration itself can mediate the occurrence of the FIE. We aimed to clarify this issue by manipulating the configural information parametrically using six different ratios, ranging from 4% to 24%. Participants were asked to judge whether a pair of faces were entirely identical or different. The paired faces that were to be compared were presented either simultaneously (Experiment 1) or sequentially (Experiment 2). Both experiments revealed that the FIE was observed only when the ratio of configural alteration was in the intermediate range. These results indicate that even though the FIE has been frequently adopted as an index to examine the underlying mechanism of face processing, the emergence of the FIE is not robust with any configural alteration but dependent on the ratio of configural alteration.

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