keyword
MENU ▼
Read by QxMD icon Read
search

Designer Receptor Exclusively Activated by a Designer Drug (DREADD)

keyword
https://www.readbyqxmd.com/read/28218623/dreadding-proglucagon-neurons-a-fresh-look-at-metabolic-regulation-by-the-brain
#1
Jonathan E Campbell, David A D'Alessio
Glucagon-like peptide 1 receptor (GLP-1R) signaling in the CNS has been linked to reduced food intake, lower body weight, improved glucose homeostasis, and activation of CNS stress axes. GLP-1 is produced by cells that express proglucagon (GCG); however, the stimuli that activate GCG+ neurons are not well known, which has made understanding the role of this neuronal population in the CNS a challenge. In this issue of the JCI, Gaykema et al. use designer receptors exclusively activated by designer drugs (DREADD) technology to specifically activate GCG+ neurons in mouse models...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28176786/disrupted-glutamatergic-transmission-in-prefrontal-cortex-contributes-to-behavioral-abnormality-in-an-animal-model-of-adhd
#2
Jia Cheng, Aiyi Liu, Michael Y Shi, Zhen Yan
Spontaneously hypertensive rats (SHR) are the most widely used animal model for the study of attention deficit hyperactivity disorder (ADHD). Here we sought to reveal the neuronal circuits and molecular basis of ADHD and its potential treatment using SHR. Combined electrophysiological, biochemical, pharmacological, chemicogenetic and behavioral approaches were utilized. We found that AMPAR-mediated synaptic transmission in pyramidal neurons of prefrontal cortex (PFC) was diminished in SHR, which was correlated with the decreased surface expression of AMPAR subunits...
February 8, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28167604/gs-dreadd-knock-in-mice-for-tissue-specific-temporal-stimulation-of-camp-signaling
#3
Dmitry Akhmedov, Maria G Mendoza-Rodriguez, Kavitha Rajendran, Mario Rossi, Jürgen Wess, Rebecca Berdeaux
Hundreds of hormones and ligands stimulate cAMP signaling in different tissues through activation of G protein-coupled receptors (GPCRs). Although functions and individual effectors of cAMP signaling are well characterized in many tissues, pleiotropic effects of GPCR agonists limit investigation of physiologic functions of cAMP signaling in individual cell types at different developmental stages in vivo To facilitate studies of cAMP signaling in specific cell populations in vivo, we harnessed the power of DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technology by creating ROSA26-based knock-in mice for conditional expression of a Gs-coupled DREADD (rM3Ds-GFP, or "GsD")...
February 6, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28138563/ganglionic-gfap-glial-gq-gpcr-signaling-enhances-heart-functions-in-vivo
#4
Alison Xiaoqiao Xie, Jakovin J Lee, Ken D McCarthy
The sympathetic nervous system (SNS) accelerates heart rate, increases cardiac contractility, and constricts resistance vessels. The activity of SNS efferent nerves is generated by a complex neural network containing neurons and glia. Gq G protein-coupled receptor (Gq-GPCR) signaling in glial fibrillary acidic protein-expressing (GFAP(+)) glia in the central nervous system supports neuronal function and regulates neuronal activity. It is unclear how Gq-GPCR signaling in GFAP(+) glia affects the activity of sympathetic neurons or contributes to SNS-regulated cardiovascular functions...
January 26, 2017: JCI Insight
https://www.readbyqxmd.com/read/28092807/application-of-the-dreadd-technique-in-biomedical-brain-research
#5
REVIEW
Grzegorz Dobrzanski, Małgorzata Kossut
The DREADD (Designer Receptors Exclusively Activated by Designer Drugs) technique is a new chemogenetic approach allowing for selective and remote control of neural activity with a high degree of spatial resolution. Since its discovery in 2007 the DREADD technique was successfully employed into basic research, and together with the optogenetic method provided so far the best tool to influence the activity of the brain circuits and cell populations. The first aim of this review was to concisely describe the technique with regard to such issues like the history of its development, biochemistry as well as modes of the designer receptors delivery and expression...
October 29, 2016: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28077715/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#6
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN) and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We demonstrated previously that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we used neuroanatomical tracing, immunofluorescence, and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections coexpress vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
January 11, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28053227/a-hypothalamic-circuit-that-controls-body-temperature
#7
Zheng-Dong Zhao, Wen Z Yang, Cuicui Gao, Xin Fu, Wen Zhang, Qian Zhou, Wanpeng Chen, Xinyan Ni, Jun-Kai Lin, Juan Yang, Xiao-Hong Xu, Wei L Shen
The homeostatic control of body temperature is essential for survival in mammals and is known to be regulated in part by temperature-sensitive neurons in the hypothalamus. However, the specific neural pathways and corresponding neural populations have not been fully elucidated. To identify these pathways, we used cFos staining to identify neurons that are activated by a thermal challenge and found induced expression in subsets of neurons within the ventral part of the lateral preoptic nucleus (vLPO) and the dorsal part of the dorsomedial hypothalamus (DMD)...
January 4, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28004955/medial-orbitofrontal-cortex-modulates-associative-learning-between-environmental-cues-and-reward-probability
#8
Sam Hall-McMaster, Jessica Millar, Ming Ruan, Ryan D Ward
It has recently been recognized that orbitofrontal cortex has 2 subdivisions that are anatomically and functionally distinct. Most rodent research has focused on the lateral subdivision, leaving the medial subdivision (mOFC) relatively unexplored. We recently showed that inhibiting mOFC neurons eliminated the differential impact of reward probability cues on discrimination accuracy in a sustained attention task. In the present study, we tested whether increasing mOFC neuronal activity in rats would accelerate acquisition of reward contingencies...
February 2017: Behavioral Neuroscience
https://www.readbyqxmd.com/read/27974613/a-novel-multisensory-integration-task-reveals-robust-deficits-in-rodent-models-of-schizophrenia-converging-evidence-for-remediation-via-nicotinic-receptor-stimulation-of-inhibitory-transmission-in-the-prefrontal-cortex
#9
Jacob M Cloke, Robin Nguyen, Beryl Y T Chung, David I Wasserman, Stephanie De Lisio, Jun Chul Kim, Craig D C Bailey, Boyer D Winters
: Atypical multisensory integration is an understudied cognitive symptom in schizophrenia. Procedures to evaluate multisensory integration in rodent models are lacking. We developed a novel multisensory object oddity (MSO) task to assess multisensory integration in ketamine-treated rats, a well established model of schizophrenia. Ketamine-treated rats displayed a selective MSO task impairment with tactile-visual and olfactory-visual sensory combinations, whereas basic unisensory perception was unaffected...
December 14, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27956747/acute-engagement-of-gq-mediated-signaling-in-the-bed-nucleus-of-the-stria-terminalis-induces-anxiety-like-behavior
#10
C M Mazzone, D Pati, M Michaelides, J DiBerto, J H Fox, G Tipton, C Anderson, K Duffy, J M McKlveen, J A Hardaway, S T Magness, W A Falls, S E Hammack, Z A McElligott, Y L Hurd, T L Kash
The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27939976/inhibiting-medial-septal-cholinergic-neurons-with-dreadd-alleviated-anxiety-like-behaviors-in-mice
#11
Yu Zhang, Ying-Ying Jiang, Shan Shao, Chan Zhang, Feng-Yu Liu, You Wan, Ming Yi
Cholinergic neurons in the medial septum (MS) participate in a variety of cognitive and emotional behaviors. Some studies but not others show that lesions or inhibition of the MS reduce anxiety-like behaviors and locomotive exploration in rats. However, these conclusions come from manipulations that are either irreversible or non-specific to cholinergic neurons, casting doubt on their validity. With DREADD (designer receptors exclusively activated by designer drugs), we temporarily and reversibly inhibited cholinergic neurons in the MS...
December 6, 2016: Neuroscience Letters
https://www.readbyqxmd.com/read/27922009/pet-imaging-guided-chemogenetic-silencing-reveals-a-critical-role-of-primate-rostromedial-caudate-in-reward-evaluation
#12
Yuji Nagai, Erika Kikuchi, Walter Lerchner, Ken-Ichi Inoue, Bin Ji, Mark A G Eldridge, Hiroyuki Kaneko, Yasuyuki Kimura, Arata Oh-Nishi, Yukiko Hori, Yoko Kato, Toshiyuki Hirabayashi, Atsushi Fujimoto, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Tetsuya Suhara, Makoto Higuchi, Masahiko Takada, Barry J Richmond, Takafumi Minamimoto
The rostromedial caudate (rmCD) of primates is thought to contribute to reward value processing, but a causal relationship has not been established. Here we use an inhibitory DREADD (Designer Receptor Exclusively Activated by Designer Drug) to repeatedly and non-invasively inactivate rmCD of macaque monkeys. We inject an adeno-associated viral vector expressing the inhibitory DREADD, hM4Di, into the rmCD bilaterally. To visualize DREADD expression in vivo, we develop a non-invasive imaging method using positron emission tomography (PET)...
December 6, 2016: Nature Communications
https://www.readbyqxmd.com/read/27917685/phosphodiesterase-10-inhibitors-in-clinical-development-for-cns-disorders
#13
Hugo Geerts, Athan Spiros, Patrick Roberts
Phosphodiesterase 10 inhibitors (PDE10-I), are conceptually attractive drugs with a potential great therapeutic window as their enriched striatal localization may likely stimulate D1R and reduce D2R downstream effects. However, so far selective PDE10-I with efficacy in animal models have not shown benefit in clinical trials and unexpectedly revealed a substantial dyskinesia motor side-effect. Areas covered: This paper reviews the underlying biological rationale of PDE10 as a target in schizophrenia, Parkinson's and Huntington's disease based on peer-reviewed published articles, the status of the different PDE10-I in clinical development for various CNS indications and explores possible reasons for the clinical trial failures and translational disconnect...
December 10, 2016: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#14
Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong-Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J Richmond, Tetsuya Suhara, Makoto Higuchi
: Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [(11)C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI)...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27909096/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#15
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN), and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We previously demonstrated that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we use neuroanatomical tracing, immunofluorescence and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections co-express vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27890661/studying-brain-regulation-of-immunity-with-optogenetics-and-chemogenetics-a-new-experimental-platform
#16
REVIEW
Tamar Ben-Shaanan, Maya Schiller, Asya Rolls
The interactions between the brain and the immune system are bidirectional. Nevertheless, we have far greater understanding of how the immune system affects the brain than how the brain affects immunity. New technological developments such as optogenetics and chemogenetics (using DREADDs; Designer Receptors Exclusively Activated by Designer Drugs) can bridge this gap in our understanding, as they enable an unprecedented mechanistic and systemic analysis of the communication between the brain and the immune system...
November 24, 2016: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27866960/ethanol-seeking-behavior-is-expressed-directly-through-an-extended-amygdala-to-midbrain-neural-circuit
#17
Melanie M Pina, Christopher L Cunningham
Abstinent alcohol-dependent individuals experience an enduring sensitivity to cue-induced craving and relapse to drinking. There is considerable evidence indicating that structures within the midbrain and extended amygdala are involved in this process. Individually, the ventral tegmental area (VTA) and the bed nucleus of the stria terminalis (BNST) have been shown to modulate cue-induced ethanol-seeking behavior. It is hypothesized that cue-induced seeking is communicated through a direct projection from the BNST to VTA...
January 2017: Neurobiology of Learning and Memory
https://www.readbyqxmd.com/read/27822508/clozapine-n-oxide-administration-produces-behavioral-effects-in-long-evans-rats-implications-for-designing-dreadd-experiments
#18
Duncan A A MacLaren, Richard W Browne, Jessica K Shaw, Sandhya Krishnan Radhakrishnan, Prachi Khare, Rodrigo A España, Stewart D Clark
Clozapine N-oxide (CNO) is a ligand for a powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Designer Drugs (DREADD) system. This system consists of synthetic G-protein-coupled receptors, which are not believed to be activated by any endogenous ligand, but are activated by the otherwise inert CNO. However, it has previously been shown that the administration of CNO in humans and rats leads to detectable levels of the bioactive compounds clozapine and N-desmethylclozapine (N-Des)...
September 2016: ENeuro
https://www.readbyqxmd.com/read/27798132/gi-dreadd-expression-in-peripheral-nerves-produces-ligand-dependent-analgesia-as-well-as-ligand-independent-functional-changes-in-sensory-neurons
#19
Jami L Saloman, Nicole N Scheff, Lindsey M Snyder, Sarah E Ross, Brian M Davis, Michael S Gold
: Designer receptors exclusively activated by designer drugs (DREADDs) are an advanced experimental tool that could potentially provide a novel approach to pain management. In particular, expression of an inhibitory (Gi-coupled) DREADD in nociceptors might enable ligand-dependent analgesia. To test this possibility, TRPV1-cre mice were used to restrict expression of Gi-DREADDs to predominantly C-fibers. Whereas baseline heat thresholds in both male and female mice expressing Gi-DREADD were normal, 1 mg/kg clozapine-N-oxide (CNO) produced a significant 3 h increase in heat threshold that returned to baseline by 5 h after injection...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27759104/single-and-transient-ca-2-peaks-in-podocytes-do-not-induce-changes-in-glomerular-filtration-and-perfusion
#20
Sybille Koehler, Sebastian Brähler, Alexander Kuczkowski, Julia Binz, Matthias J Hackl, Henning Hagmann, Martin Höhne, Merly C Vogt, Claudia M Wunderlich, F Thomas Wunderlich, Frank Schweda, Bernhard Schermer, Thomas Benzing, Paul T Brinkkoetter
Chronic alterations in calcium (Ca(2+)) signalling in podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca(2+) peaks influence glomerular biology and cause podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by a Designer Drug) knock-in mouse line to manipulate intracellular Ca(2+) levels. By mating to a podocyte-specific Cre driver we are able to investigate the impact of Ca(2+) peaks on podocyte biology in living animals...
October 19, 2016: Scientific Reports
keyword
keyword
62183
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"