A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo

Dong, Ao; He, Kaikai; Dudok, Barna; Farrell, Jordan S.; Guan, Wuqiang; Liput, Daniel J.; Puhl, Henry L.; Cai, Ruyi; Wang, Huan; Duan, Jiali; Albarran, Eddy; Ding, Jun; Lovinger, David M.; Li, Bo; Soltész, Iván; Li, Yulong

doi:10.1038/s41587-021-01074-4

Cited by 117 publications

(97 citation statements)

References 84 publications

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“…Recently, there has been a breakthrough in this research field. Dong et al (2021) developed a genetically encoded tool for sensing endocannabinoids based on the human CB 1 receptor and circular-permutated GFP, named GRABeCB2.0. The range of fluorescence change of this protein is sufficient for the detection of physiological endocannabinoid concentrations, and has a rise time and decay time of 1.6 and 11.2 s, respectively ( Dong et al, 2021 ).…”

Section: Endocannabinoidsmentioning

confidence: 99%

“… Dong et al (2021) developed a genetically encoded tool for sensing endocannabinoids based on the human CB 1 receptor and circular-permutated GFP, named GRABeCB2.0. The range of fluorescence change of this protein is sufficient for the detection of physiological endocannabinoid concentrations, and has a rise time and decay time of 1.6 and 11.2 s, respectively ( Dong et al, 2021 ). Furthermore, the GRABeCB2.0 sensor binds endocannabinoids such as 2-AG and AEA, but does not couple to the downstream G proteins and has no observable effects on cellular physiology ( Dong et al, 2021 ).…”

Section: Endocannabinoidsmentioning

confidence: 99%

“…The range of fluorescence change of this protein is sufficient for the detection of physiological endocannabinoid concentrations, and has a rise time and decay time of 1.6 and 11.2 s, respectively ( Dong et al, 2021 ). Furthermore, the GRABeCB2.0 sensor binds endocannabinoids such as 2-AG and AEA, but does not couple to the downstream G proteins and has no observable effects on cellular physiology ( Dong et al, 2021 ). These features enable us to use this sensor to observe physiological endocannabinoid release in cultures, brain slices and the brain of live animals during behavioral experiments ( Dong et al, 2021 ; Farrell et al, 2021 ).…”

Section: Endocannabinoidsmentioning

confidence: 99%

“…Furthermore, the GRABeCB2.0 sensor binds endocannabinoids such as 2-AG and AEA, but does not couple to the downstream G proteins and has no observable effects on cellular physiology ( Dong et al, 2021 ). These features enable us to use this sensor to observe physiological endocannabinoid release in cultures, brain slices and the brain of live animals during behavioral experiments ( Dong et al, 2021 ; Farrell et al, 2021 ). For example, spontaneous running induces an increase in the signal for 2-AG release in the pyramidal cell layer of the hippocampal CA1 in mice ( Farrell et al, 2021 ).…”

Section: Endocannabinoidsmentioning

confidence: 99%

“…Similarly, the 2-AG level in brain tissues 100 min after kainate treatment in 8-week-old rats was 1.5-fold higher than that in vehicle-treated controls ( Fezza et al, 2014 ). Recently, the endocannabinoid sensor GRABeCB2.0 has been developed ( Dong et al, 2021 ). By imaging fluorescent signals representing released endocannabinoids by using GRABeCB2.0, a transient surge of endocannabinoid release was successfully detected during afterdischarges evoked by the electrical stimulation of the contralateral hippocampus ( Farrell et al, 2021 ).…”

Section: Epileptogenesismentioning

confidence: 99%

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Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

Sugaya

Kano

2022

Front. Neural Circuits

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Research on endocannabinoid signaling has greatly advanced our understanding of how the excitability of neural circuits is controlled in health and disease. In general, endocannabinoid signaling at excitatory synapses suppresses excitability by inhibiting glutamate release, while that at inhibitory synapses promotes excitability by inhibiting GABA release, although there are some exceptions in genetically epileptic animal models. In the epileptic brain, the physiological distributions of endocannabinoid signaling molecules are disrupted during epileptogenesis, contributing to the occurrence of spontaneous seizures. However, it is still unknown how endocannabinoid signaling changes during seizures and how the redistribution of endocannabinoid signaling molecules proceeds during epileptogenesis. Recent development of cannabinoid sensors has enabled us to investigate endocannabinoid signaling in much greater spatial and temporal details than before. Application of cannabinoid sensors to epilepsy research has elucidated activity-dependent changes in endocannabinoid signaling during seizures. Furthermore, recent endocannabinoid research has paved the way for the clinical use of cannabidiol for the treatment of refractory epilepsy, such as Dravet syndrome, Lennox-Gastaut syndrome and tuberous sclerosis complex. Cannabidiol significantly reduces seizures and is considered to have comparable tolerability to conventional antiepileptic drugs. In this article, we introduce recent advances in research on the roles of endocannabinoid signaling in epileptic seizures and discuss future directions.

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Section: Endocannabinoidsmentioning

confidence: 99%

Section: Endocannabinoidsmentioning

confidence: 99%

Section: Endocannabinoidsmentioning

confidence: 99%

Section: Endocannabinoidsmentioning

confidence: 99%

Section: Epileptogenesismentioning

confidence: 99%

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Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

Sugaya

Kano

2022

Front. Neural Circuits

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Planted Graphene Quantum Dots for Targeted, Enhanced Tumor Imaging and Long‐Term Visualization of Local Pharmacokinetics

Wang

et al. 2023

Advanced Materials

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While photoluminescent graphene quantum dots (GQDs) have long been considered very suitable for bioimaging owing to their protein‐like size, superhigh photostability and in vivo long‐term biosafety, their unique and crucial bioimaging applications in vivo remain unreachable. Herein, planted GQDs are presented as an excellent tool for in vivo fluorescent, sustainable and multimodality tumor bioimaging in various scenarios. The GQDs are in situ planted in the poly(ethylene glycol) (PEG) layer of PEGylated nanoparticles via a bottom‐up molecular approach to obtain the NPs‐GQDs‐PEG nanocomposite. The planted GQDs show more than four times prolonged blood circulation and 7–8 times increased tumor accumulation than typical GQDs in vivo. After accessible specificity modification, the multifunctional NPs‐GQDs‐PEG provides targeted, multimodal molecular imaging for various tumor models in vitro or in vivo. Moreover, the highly photostable GQDs enable long‐term, real‐time visualization of the local pharmacokinetics of NPs in vivo. Planting GQDs in PEGylated nanomedicine offers a new strategy for broad in vivo biomedical applications of GQDs.

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A Portable Fluorescence Sensor with Improved Performance for Aniline Monitoring

Gao

Huang

Fang

et al. 2022

Adv Materials Inter

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Among them, fluorescent sensors have attracted most attention of scientists due to their outstanding advantages, such as high sensitivity, low cost, excellent selectivity, ease of sensor preparation, etc. [4][5][6][7][8] In the sensing process, the first excited electronic state of a luminogen presents high sensibility to surrounding microenvironments including temperature, pressure, relative humidity (RH), and solvent polarity, thus the luminogens are of great significance. [9][10][11][12][13][14] Rylene diimides (RDIs), as one of the most important families of dye molecules, have been extensively studied due to their electron-accepting capacity and conducting properties. [15,16] There are various classes of RDIs, such as pyromellitic diimide (PMI), [17] 1,4,5,8-naphthalenediimide (NDI), [18] pyrene diimide (PYI), [19] perylene tetracarboxylic diimide (PDI), [20] and other larger diimides. [21] Among them, PMIs with an aromatic ring in the center and the tetracarboxylic diimides on the sides of the ring have drawn much attention. [22] PMI derivatives could be easily synthesized through a single-step reaction of the pyromellitic dianhydride and the amines, which facilitates the large-scale preparation owing to the high conversion yield and ease of purification procedures. [23] Nevertheless, However, due to the low fluorescence quantum yield and poor photostability of PMI derivatives, much fewer attempts have been made to fabricate fluorescence sensors based on PMI derivatives compared with NDI and PDI derivatives. Thus, it is still challenging to design and synthesize PMI-based luminogens that exhibit excellent photophysical characteristics, such as high luminescence, photostability, and high response specificity, for their applications in fluorescent sensors.In this work, we design and synthesize o-carborane modified pyromellitic diimide derivative (CB-PMI) fluorescent materials with enhanced amine-response, which offers the possibility for real-time and visual detection of lung cancer. A representative molecule CB-PMI consists of a PMI core, two phenyl rings (π-bridge), and two o-carborane units (Scheme 1). The o-carborane moieties with 3D topology are introduced to enhance the photostability and modulate the molecular energy gap of the PMI derivative. [24][25][26] Photophysical properties of as-synthesized CB-PMI both in the solution and solid states were carefully investigated. Subsequently, the sensing performance of CB-PMI Aniline is an important biomarker in human exhaled breath for lung cancer, thus aniline sensing is of paramount importance. However, highly sensitive and selective detection of aniline in high moisture environment of exhaled breath is still challenging. In this work, a new fluorescence sensor for aniline with ultrahigh sensitivity is constructed. The o-carborane modified pyromellitic diimide derivative (CB-PMI) is designed and prepared as the sensitive layer for the fluorescence sensor. As-prepared sensing films exhibit a highly improved response toward aniline vapor. The good sensing per...

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A fluorescent sensor for spatiotemporally resolved imaging of endocannabinoid dynamics in vivo

Cited by 117 publications

References 84 publications

Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

Endocannabinoid-Mediated Control of Neural Circuit Excitability and Epileptic Seizures

Planted Graphene Quantum Dots for Targeted, Enhanced Tumor Imaging and Long‐Term Visualization of Local Pharmacokinetics

A Portable Fluorescence Sensor with Improved Performance for Aniline Monitoring

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