Dynamic regulation of the cholinergic system in the spinal central nervous system

Rima, Mohamad; Lattouf, Y.; Younes, Maroun Abi; Bullier, Erika; Legendre, Pascal; Hong, Elim

doi:10.1038/s41598-020-72524-3

Cited by 23 publications

(9 citation statements)

References 59 publications

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“…Due to zebrafish genome duplication, this enzyme is encoded by two genes, chata and chatb , that are differentially expressed in different types of neurons. However, generally, chata is the only one expressed in early larval stage 38 as also demonstrated by our gene expression analysis. Indeed, the expression of both genes were examined by real-time PCR, but the analysis demonstrated detectable levels only for the chata gene.…”

Section: Resultssupporting

confidence: 82%

Melanoma innervation is associated with cancer progression in a zebrafish xenograft model

Lorenzini,

Marines,

Friec

et al. 2023

Preprint

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The peripheral nervous system has a key role in regulating tumour biology in different types of cancer. Here, by modelling aggressive melanoma in larval zebrafish xenografts, we highlight the dynamics of tumour innervation in the tumour microenvironment (TME). Axonogenesis and dendritogenesis are detected in the motoneurons surrounding the melanoma niche and neurogenesis is observed in the nearby population of the enteric nervous system. We also demonstrate the crucial role of catecholamines in promoting melanoma progression, supportingin vivocancer cell dissemination and invasion. Thiszebrafishmodel will allow to uncover neural markers associated with melanoma progression to help in the design of innovative anti-neurogenic therapies targeting specifically the neuronal signals that regulate melanoma progression.Graphical abstractHighlightsTransplantation of human melanoma cells in 3 dpf zebrafish swim bladder allows the development of aggressive melanoma, which cells invade the surrounding organs and migrate over distant locations.The presence of melanoma cells in the larval zebrafish induces morphological changes in the motoneurons inside the tumour niche, including increased axon length and dendritic arborization.The invasion of melanoma cells in the larval intestine promotes neurogenesis of enteric neurons.Transplanted melanoma cells display direct contact with enteric neurons in the intestinal region and migrate along axons to escape from the primary cancer mass, as a mechanism similar to vessel co-option during metastatic dissemination.Catecholamines promote melanoma cell migration and invasion in the zebrafish, modelling melanoma progression.

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Section: Resultssupporting

confidence: 82%

Melanoma innervation is associated with cancer progression in a zebrafish xenograft model

Lorenzini,

Marines,

Friec

et al. 2023

Preprint

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“…However, one scenario can be suggested in which M. bornmuelleri ’s venom interferes with cholinergic signaling. In fact, cholinergic neurons are well reported in one-day-old zebrafish embryos [ 34 ], and proper cholinergic signaling is important for spontaneous zebrafish coiling [ 35 ]. As such, bajan mutants, resulting from a point mutation in the gene coding choline acetyltransferase, which is the enzyme responsible for acetylcholine synthesis, lack the coiling movement [ 35 ].…”

Section: Discussionmentioning

confidence: 99%

Neuro- and Cardiovascular Activities of Montivipera bornmuelleri Snake Venom

Sahyoun

Krężel

Mattei

et al. 2022

Biology

Self Cite

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The complications following snake bite envenoming are due to the venom’s biological activities, which can act on different systems of the prey. These activities arise from the fact that snake venoms are rich in bioactive molecules, which are also of interest for designing drugs. The venom of Montivipera bornmuelleri, known as the Lebanon viper, has been shown to exert antibacterial, anticancer, and immunomodulatory effects. However, the venom’s activity on the nervous system has not yet been studied, and its effect on the cardiovascular system needs further investigation. Because zebrafish is a convenient model to study tissue alterations induced by toxic agents, we challenged it with the venom of Montivipera bornmuelleri. We show that this venom leads to developmental toxicity but not teratogenicity in zebrafish embryos. The venom also induces neurotoxic effects and disrupts the zebrafish cardiovascular system, leading to heartbeat rate reduction and hemorrhage. Our findings demonstrate the potential neurotoxicity and cardiotoxicity of M. bornmuelleri’s venom, suggesting a multitarget strategy during envenomation.

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“…Such evidence could imply that the zebrafish cholinergic neurotransmission system (and, subsequently, the effects of cholinergic agents) differs anatomically and/or physiologically from that of H. sapiens . In vertebrates, cholinergic neurons are present in distinct areas of the brain, including the basal forebrain, the brainstem, and the habenula [ 59 ]. It is known that the functional equivalents of the mammalian amygdala, striatum, and hippocampus are represented in the zebrafish brain by the medial zone of the dorsal telencephalon, the dorsal nucleus of the ventral telencephalon [ 60 ], and the lateral zone of the dorsal telencephalon, respectively [ 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

et al. 2022

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Chromone-containing allylmorpholines (CCAMs) are a novel class of compounds that have demonstrated acetyl- and butyryl-cholinesterase-inhibiting and N-methyl-D-aspartate (NMDA) receptor-blocking properties in vitro, but their in vivo pharmacological activity remains underexplored. In this work, we evaluated the psychotropic activity of five different CCAMs (1 (9a), 2 (9j), 3 (9l), 4 (33a), and 5 (33b)) using the novel tank test (NTT) and light/dark box (LDB) test in adult zebrafish. The CCAMs were screened in the NTT at a range of concentrations, and they were found to induce a dose-dependent sedative effect. Compound 4 (33a) was also evaluated using the LDB test, and it was found to have anxiolytic-like properties at low concentrations. To assess the potential contribution of the glutamate and cholinergic mechanisms in the effects of the CCAMs, we conducted experiments with pre-exposure to putative antagonists, NMDA and biperiden. Neither biperiden nor NMDA were able to diminish or cancel the effects of the CCAMs, countering the in vitro data obtained in previous studies. The apparent discrepancy could be related to the specifics of CCAM metabolism or to the interspecies differences between the putative target proteins, possibly due to the relatively low identity percentage of their sequences. Although further research in mammals is required in order to establish their pharmacological properties, novel CCAMs may represent an appealing group of psychoactive drug candidates.

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Dynamic regulation of the cholinergic system in the spinal central nervous system

Cited by 23 publications

References 59 publications

Melanoma innervation is associated with cancer progression in a zebrafish xenograft model

Melanoma innervation is associated with cancer progression in a zebrafish xenograft model

Neuro- and Cardiovascular Activities of Montivipera bornmuelleri Snake Venom

Novel Chromone-Containing Allylmorpholines Induce Anxiolytic-like and Sedative Effects in Adult Zebrafish

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