A Drosophila model for developmental nicotine exposure

Velazquez-Ulloa, Norma

doi:10.1371/journal.pone.0177710

Cited by 24 publications

(30 citation statements)

References 74 publications

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“…Nicotine is a well−studied developmental neuroteratogen in humans 29 , non-human primates 31 , and invertebrates 32 . A fundamental gap in this area is the lack of mechanistic knowledge of how the effects on individual cell physiology result in impaired cognitive function.…”

Section: Discussionmentioning

confidence: 99%

“…Nicotine is a well-known neuroteratogen: embryonic exposure to nicotine leads to severe brain morphological defects as well as significant postnatal deficits in cognitive functions 29 – 32 . The majority of these effects of nicotine occur through its action on nicotinic acetyl choline (nAChR) receptors, but it is not known how this bioelectric change at the single-cell level alters whole organ morphogenesis of the brain.…”

Section: Introductionmentioning

confidence: 99%

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HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns

et al. 2018

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Endogenous bioelectrical signaling coordinates cell behaviors toward correct anatomical outcomes. Lack of a model explaining spatialized dynamics of bioelectric states has hindered the understanding of the etiology of some birth defects and the development of predictive interventions. Nicotine, a known neuroteratogen, induces serious defects in brain patterning and learning. Our bio-realistic computational model explains nicotine’s effects via the disruption of endogenous bioelectrical gradients and predicts that exogenous HCN2 ion channels would restore the endogenous bioelectric prepatterns necessary for brain patterning. Voltage mapping in vivo confirms these predictions, and exogenous expression of the HCN2 ion channel rescues nicotine-exposed embryos, resulting in normal brain morphology and molecular marker expression, with near-normal learning capacity. By combining molecular embryology, electrophysiology, and computational modeling, we delineate a biophysical mechanism of developmental brain damage and its functional rescue.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns

et al. 2018

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“…1. Cechy pszczoły miodnej potwierdzające jej przydatność jako organizmu modelowego (138) oraz C. elegans (37). Ponadto, bardzo często jako etap wstępny stosuje się alternatywny model badawczy -hodowle tkankowe (np.…”

Section: Tab 1 Zestawienie Optymalnych Warunków Klimatycznych I Obsunclassified

Honey bee as an alternative model invertebrate organism

Łoś¹,

Bieńkowska²,

Strachecka³

2025

Medycyna Weterynaryjna

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Insects perfectly fit the flagship principle of animal research – 3R: to reduce (the number of animals), to replace (animals with alternative models) and to refine (methods). Bees have the most important advantages of a model organism: they cause minimal ethical controversy, they have a small and fully known genome, and they permit the use of many experimental techniques. Bees have a fully functional DNMT toolkit. Therefore, they are used as models in biomedical/genetic research, e.g. in research on the development of cancer or in the diagnostics of mental and neuroleptic diseases in humans. The reversion of aging processes in bees offers hope for progress in gerontology research. The cellular mechanisms of learning and memory coding, as well as the indicators of biochemical immunity parameters, are similar or analogous to those in humans, so bees may become useful in monitoring changes in behavior and metabolism. Bees are very well suited for studies on the dose of the substance applied to determine the lethal dose or the effect of a formula on life expectancy. Honeybees have proven to be an effective tool for studying the effects of a long-term consumption of stimulants, as well as for observing behavioral changes and developing addictions at the individual and social levels, as well as for investigating the effects of continuously delivering the same dose of a substance. The genomic and physiological flexibility of bees in dividing tasks among workers in a colony makes it possible to create a Single- Cohort Colony (SCC) in which peers compared perform different tasks. Moreover behavioral methods (e.g. Proboscis Extension Reflex – PER, Sting Extension Reflex – SER, free flying target discrimination tasks or the cap pushing response) make it possible to analyse changes occurring in honeybee brains during learning and remembering. Algorithms of actions are created based on the behavior of a colony or individual, e.g. Artificial Bee Colony Algorithm (ABCA). Honeybees are also model organisms for profiling the so-called intelligence of a swarm or collective intelligence. Additionally, they serve as models for guidance systems and aviation technologies. Bees have inspired important projects in robotics, such as B-droid, Robobee and The Green Brain Project. It has also been confirmed that the apian sense of smell can be used to detect explosive devices, such as TNT, or drugs (including heroin, cocaine, amphetamines and cannabis). This inconspicuous little insect can revolutionize the world of science and contribute to the solution of many scientific problems as a versatile model.

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“…To test this model, we exposed wild-type larvae to different doses (0.1 and 0.5 mg/ml) of nicotine 36 , an agonist of nAcRs, for 24 h. In these larvae, the nAcRβ2 level is increased to 2-fold that of control larvae. We saw a striking ~10-fold increase in miR-1010 levels for both dosage conditions (Fig.…”

Section: Mir-1010/skip Upregulation Is Specific To Nacrβ2-mediated Inmentioning

confidence: 99%

The mirtron miR-1010 functions in concert with its host gene SKIP to balance elevation of nAcRβ2

Amourda

Saunders

2020

Sci Rep

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Mirtrons are non-canonical miRNAs arising by splicing and debranching from short introns. A plethora of introns have been inferred by computational analyses as potential mirtrons. Yet, few have been experimentally validated and their functions, particularly in relation to their host genes, remain poorly understood. Here, we found that Drosophila larvae lacking either the mirtron miR-1010 or its binding site in the nicotinic acetylcholine receptor β2 (nAcRβ2) 3′UTR fail to grow properly and pupariate. Increase of cortical nAcRβ2 mediated by neural activity elevates the level of intracellular Ca 2+ , which in turn activates CaMKII and, further downstream, the transcription factor Adf-1. We show that miR-1010 downregulates nAcRβ2. We reveal that Adf-1 initiates the expression of SKIP, the host gene of miR-1010. Preventing synaptic potentials from overshooting their optimal range requires both SKIP to temper synaptic potentials (incoherent feedforward loop) and miR-1010 to reduce nAcRβ2 mRNA levels (negative feedback loop). Our results demonstrate how a mirtron, in coordination with its host gene, contributes to maintaining appropriate receptor levels, which in turn may play a role in maintaining homeostasis.

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A Drosophila model for developmental nicotine exposure

Cited by 24 publications

References 74 publications

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns

HCN2 Rescues brain defects by enforcing endogenous voltage pre-patterns

Honey bee as an alternative model invertebrate organism

The mirtron miR-1010 functions in concert with its host gene SKIP to balance elevation of nAcRβ2

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