Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators

Z, Wu; Lin, Dayu; Li, Yulong

doi:10.1038/s41583-022-00577-6

Cited by 123 publications

(112 citation statements)

References 181 publications

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“…Furthermore, Yulong Li's group has made significant progress in developing a number of genetically encoded fluorescent indicators, emphasizing how these novel biosensors can be used in uncovering functional roles of neurotransmitters and neuromodulators in the nervous system and potentially peripheral malignancies. [ 283 ]…”

Section: Current Research Strategies and Future Directionsmentioning

confidence: 99%

Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

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highly dynamic network of various cell types (e.g., cancer cells, endothelial cells, immune cells, fibroblasts) that exert differential effects on neuronal activity within the local environment. Thus, complex signaling between cancer and stromal cells in the TME results in altered firing rates of local nerves. Reciprocally, increased neuronal activity and subsequent release of classical neurotransmitters and/or neuropeptides within the TME results in enhanced cancer progression and subsequent metastasis in various preclinical models and clinical studies. [5][6][7][8][9] Nerves interact with multiple stromal cells in the TME where they indirectly promote tumor growth, progression, and subsequent metastasis. [10] Several studies have demonstrated that sympathetic nerve innervation and subsequent release of the neurotransmitter norepinephrine (NE) is increased in breast tumors. [6,8,9] However, recent work has demonstrated that there is an inverse relationship between tumor weight and norepinephrine content (i.e., larger the size of the tumor, the lower the levels of NE), despite increased innervation of sympathetic nerves within the TME. [11] These findings may be attributed to a relatively unexplored phenomenon: neuropeptide release within the TME. Neuropeptides are molecular messengers that regulate a variety of functions in the central and peripheral nervous systems via binding G-protein-coupled receptors (GPCRs) on target cells. One of the many functions of neuropeptides is serving as growth factors for normal cells via the activation of the heterotrimeric G protein Gq and subsequent synthesis of second messengers and engagement of tyrosine phosphorylation cascades. Neuropeptides act as neuromodulators, in that they can alter the response of neurons to neurotransmitters and other circulating signals, such as leptin, ghrelin, glucose, and insulin-all of which are affected during cancer progression. [12][13][14][15][16][17] For example, both neuropeptide Y (NPY) and hypocretin/orexin neurons appear to mediate some of the orexigenic effects of centrally administered ghrelin as administration of NPY receptor antagonists attenuated ghrelininduced feeding. Similarly, ghrelin-induced feeding was suppressed in orexin knockout mice, indicating that ghrelin may stimulate feeding through both the orexin and NPY systems. [18] However, neuropeptide signaling is exploited within cancer cells and many studies demonstrate the contribution of neuropeptides in tumor cell proliferation and migration, [19] with many major neuropeptides also potentially contributing to cancer processes (see Table 1). Additionally, neuropeptides exert direct Neuropeptides are small regulatory molecules found throughout the body, most notably in the nervous, cardiovascular, and gastrointestinal systems. They serve as neurotransmitters or hormones in the regulation of diverse physiological processes. Cancer cells escape normal growth control mechanisms by altering their expression of growth factors, receptors, or intracellular signals, and neuropeptid...

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Section: Current Research Strategies and Future Directionsmentioning

confidence: 99%

Neuropeptides in Cancer: Friend and Foe?

Berisha

Borniger

2022

Advanced Biology

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“…Among multiple imaging modalities, fluorescence reporter genes have drawn great attention; however, penetration depths limit their in vivo application [ 3 ]. Recently, other imaging modalities, including magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and ultrasound (US) imaging, have been explored in the field of reporter genes [ 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Observing brain activity is a dream of researchers. Gene-encoded fluorescent indicators that are used to dynamically monitor neurotransmitters and neuromodulators with fluorescence imaging have recently achieved great breakthroughs and have been reviewed in excellent studies [ 3 ]. We note that, for clinical imaging modalities, such as MRI, radionuclide imaging, and US, some breakthroughs have been achieved in reporter gene-based brain studies.…”

Section: Introductionmentioning

confidence: 99%

Reporter Genes for Brain Imaging Using MRI, SPECT and PET

Gao

Wang

Gong

et al. 2022

IJMS

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The use of molecular imaging technologies for brain imaging can not only play an important supporting role in disease diagnosis and treatment but can also be used to deeply study brain functions. Recently, with the support of reporter gene technology, optical imaging has achieved a breakthrough in brain function studies at the molecular level. Reporter gene technology based on traditional clinical imaging modalities is also expanding. By benefiting from the deeper imaging depths and wider imaging ranges now possible, these methods have led to breakthroughs in preclinical and clinical research. This article focuses on the applications of magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT), and positron emission tomography (PET) reporter gene technologies for use in brain imaging. The tracking of cell therapies and gene therapies is the most successful and widely used application of these techniques. Meanwhile, breakthroughs have been achieved in the research and development of reporter genes and their imaging probe pairs with respect to brain function research. This paper introduces the imaging principles and classifications of the reporter gene technologies of these imaging modalities, lists the relevant brain imaging applications, reviews their characteristics, and discusses the opportunities and challenges faced by clinical imaging modalities based on reporter gene technology. The conclusion is provided in the last section.

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“…Recently, building on the successful G protein-coupled receptor activation-based (GRAB) strategy, our group and others independently developed a series of genetically encoded sensors for detecting a variety of neurotransmitters and neuromodulators with high sensitivity, selectivity, and spatiotemporal resolution in in vivo preparations [15][16][17][18][19] . Using this strategy, we developed a pair of genetically encoded fluorescent sensors called GRABHA1h and GRABHA1m (abbreviated here as HA1h and HA1m, respectively) based on the human H4R and water bear (tardigrade) H1R receptors, respectively, in order to measure extracellular HA with high sensitivity and high spatiotemporal resolution both in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Genetically encoded sensors for measuring histamine release both in vitro and in vivo

Dong

Yan

et al. 2022

Preprint

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Histamine (HA) is a key biogenic monoamine involved in a wide range of physiological and pathological processes in both the central nervous system and the periphery. Because the ability to directly measure extracellular HA in real-time will provide important insights into the functional role of HA in complex circuits under a variety of conditions, we developed a series of genetically encoded G protein-coupled receptor activation-based (GRAB) HA (GRABHA) sensors. These sensors produce a robust increase in fluorescence upon HA application, with good photostability, sub-second kinetics, nanomolar affinity, and high specificity. Using these GRABHA sensors, we measured electrical stimulation-evoked HA release in acute brain slices with high spatiotemporal resolution. Moreover, we recorded HA release in the preoptic area of the hypothalamus and in the medial prefrontal cortex during the sleep-wake cycle in freely moving mice, finding distinct patterns of HA release in these specific brain regions. Together, these in vitro and in vivo results show that our GRABHA sensors have high sensitivity and specificity for measuring extracellular HA, thus providing a robust new set of tools for examining the role of HA signaling in both health and disease.

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Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators

Cited by 123 publications

References 181 publications

Neuropeptides in Cancer: Friend and Foe?

Neuropeptides in Cancer: Friend and Foe?

Reporter Genes for Brain Imaging Using MRI, SPECT and PET

Genetically encoded sensors for measuring histamine release both in vitro and in vivo

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