Sensing Acetylcholine and Anticholinesterase Compounds

Schena, Alberto; Johnsson, Kai

doi:10.1002/ange.201307754

Cited by 7 publications

(5 citation statements)

References 13 publications

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“…Other methods detect ACh electrochemically -an inherently slower, indirect technique without molecular specificity 16 . Improvements in ACh detection have come from the development of semisynthetic, FRET-based probes 17,18 and whole cell-based fluorescence reporters 19 , but these are limited by low signal change, poor spatial and temporal resolution, and difficulty in delivery.…”

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confidence: 99%

A fast genetically encoded fluorescent sensor for faithfulin vivoacetylcholine detection in mice, fish, worms and flies

Zhang

Shivange

et al. 2020

Preprint

138

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Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice and in vivo preparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all animals. IntroductionAcetylcholine (ACh) is a critical neurotransmitter in all animals. Among invertebrates, it is the most prevalent excitatory transmitter in the brain, sensory ganglia, and frequently the neuromuscular junction (NMJ). Among vertebrates, only a minority of neurons release ACh, but these signals play varying key roles. For instance, ACh signals at the NMJ, in the autonomic nervous system, and in subsets of the central nervous system, particularly projections arising from the brainstem and basal forebrain. Other cholinergic neuron populations in the brain include striatal interneurons, the stria vascularis-medial habenula-interpeduncular nucleus pathway, and sparse, incompletely characterized cell types such as intrinsic cholinergic interneurons in cortex 1 and hippocampus 2 . ACh helps to regulate attention 3 and wakefulness 4 , and participates in memory formation and consolidation 5 . ACh is also an important transmitter in glia, and between the nervous and immune systems 6 .Acetylcholine is synthesized pre-synaptically from choline and acetyl-CoA by choline acetyltransferase (ChAT), then packaged into synaptic vesicles by the vesicular acetylcholine transporter (VAChT). A key, partially understood aspect of cholinergic signaling is co-release with other neurotransmitters, including GABA, ATP, and glutamate 7,8 . To understand the role of co-release, one must measure ACh release alongside emerging measurements of other neurotransmitters.Acetylcholine receptors are among the most diverse neurotransmitter receptor families. Humans possess five muscarinic G protein-coupled receptors (GPCRs) for ACh (mAChRs) with diverse expression in the brain and smooth, cardiac, and skeletal muscle. Vertebrate nicotinic ACh receptors (nAChRs) are pentameric ligand-gated cation channels. Humans have a total of 17 nAChR subunit genes, in five classes: 10 a, 4 b, and one each of g, d, and e. nAChRs occur with many subunit combinations 9 , and others may be undiscovered. Invertebrates also have AChgated chloride channels. On neurons, receptors can be localized pre-, post-, and extrasynaptically, often with different isoforms in each place 10

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confidence: 99%

A fast genetically encoded fluorescent sensor for faithfulin vivoacetylcholine detection in mice, fish, worms and flies

Zhang

Shivange

et al. 2020

Preprint

138

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“…We demonstrate adaptability of the AVATar architecture by designing an agent that detects the neurotransmitter DA. Incorporation of alternative tethered ligands and cognate binding domains could permit a variety of further vasoprobe-based sensors to be constructed, in some cases leveraging wellcharacterized components of previously described fluorescent imaging probes [26][27][28][29][30][31][32][33][34][35] .…”

Section: Discussionmentioning

confidence: 99%

“…Time courses were obtained by averaging MRI signal over 1.2 x 1.2 mm regions of interest defined around cannula tip locations in individual animals' datasets and standard error was calculated across animals using MATLAB. The plateau percent signal change was determined by comparing values observed during the baseline period with values observed after PACAP infusion (minutes [30][31][32][33][34][35][36][37][38][39][40].…”

Section: Mri Assessment Of Injected Pacap Probesmentioning

confidence: 99%

Target-responsive vasoactive probes for ultrasensitive molecular imaging

Ohlendorf

Wiśniowska

Desai

et al. 2019

Preprint

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ABSTRACTThe ability to monitor molecules volumetrically throughout the body could provide valuable biomarkers for studies of healthy function and disease, but noninvasive detection of molecular targets in living subjects often suffers from poor sensitivity or selectivity. Here we describe a family of potent imaging probes that can be activated by molecules of interest in deep tissue, providing a basis for mapping nanomolar-scale analytes without the radiation or heavy metal content associated with traditional molecular imaging agents. The probes are reversibly-caged vasodilators that induce responses detectable by hemodynamic imaging; they are constructed by combining vasoactive peptides with synthetic chemical appendages and protein blocking domains. We use this architecture to create ultrasensitive biotin-responsive imaging agents, which we apply for wide-field mapping of targets in rat brains using functional magnetic resonance imaging. We also adapt the sensor design for detecting the neurotransmitter dopamine, illustrating versatility of this approach for addressing biologically important molecules.

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“…To this end, a range of methods/techniques for detection of AChE level have been employed, including the colorimetric Ellman method 8,9 or the detection of hydrogen peroxide (H 2 O 2 ) produced by oxidation of choline. 10,11 With the development of H 2 O 2 sensors, [12][13][14] recently, uorescent or colorimetric approaches based on synthetic probes and nanozymes, [15][16][17][18] as well as various electrochemical methods, 19,20 have been developed to monitor AChE activity and screen the inhibitors of AChE. However, most of these methods cannot discriminate AChE from other biothiols.…”

Section: Introductionmentioning

confidence: 99%