Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption

Moyano, Paula; Frias, Mariano de; Lobo, Margarita; Anadón, M.J.; Sola, Emma; Pelayo, Adela; Díaz, María Jesús Villamide; Frejo, María Teresa; Pino, Javier del

doi:10.1016/j.tox.2017.12.006

Cited by 37 publications

(20 citation statements)

References 52 publications

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“…These may include death of cholinergic neurons [89], neurotoxicity induced by mechanisms other than AChE inhibition, and other types of toxicity. After absorption, Cd is known to interfere with the biological roles of several essential ions, such as calcium, zinc, and magnesium, among others, and to interact with several biological targets resulting in a wide range of toxic effects [7,11,90,91], the most part of them are partially unrevealed. Some of the effects that have been described in fish exposed to Cd, such as histological alterations in several organs [21], disruption of ion balance [92], changes in the expression of genes related with stress responses [87], cytotoxicity [93], among others [16,17,18,94] may have also contributed to the reduction of the predatory performance found in M-est juveniles exposed to Cd alone.…”

Section: Resultsmentioning

confidence: 99%

“…Although the inhibitory effect of Cd on AChE activity of several species is well known [95,96], the mechanisms involved are very complex and are not completely understood even in mammals where they have been intensively studied [e.g., 91,97,98]. Among other mechanisms likely contributing to AChE inhibition, Cd-induced oxidative stress is believed to play an important role [91,97]. In M-est juveniles exposed to Cd, the GST activity was slightly increased but not significantly different from the control group (Figure 1C).…”

Section: Resultsmentioning

confidence: 99%

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Neurotoxicity, Behavior, and Lethal Effects of Cadmium, Microplastics, and Their Mixtures on Pomatoschistus microps Juveniles from Two Wild Populations Exposed under Laboratory Conditions―Implications to Environmental and Human Risk Assessment

Miranda

Vieira

Guilhermino

2019

IJERPH

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Microplastics (MPs) were found to modulate the toxicity of other pollutants but the knowledge on the topic is still limited. The goals of this study were to investigate the short-term toxicity of cadmium (Cd) to wild Pomatochistus microps juveniles, the potential modulation of acute Cd toxicity by 1–5 µm polyethylene MPs in this species, and possible differences of sensitivity to Cd and MPs-Cd mixtures between juveniles from two distinct wild populations. Juveniles were collected in the estuaries of Minho (M-est) and Lima (L-est) Rivers (NW Portugal). One 96 h bioassay with M-est juveniles and another one with L-est juveniles were carried out in laboratory conditions. Each bioassay had 12 treatments: control, 5 Cd concentrations, 1 MPs concentration, and 5 MPs-Cd mixtures. No significant differences in Cd-induced mortality between juveniles from distinct estuaries or between juveniles exposed to Cd alone and those exposed to MPs-Cd mixtures were found. The total 96h LC10 and LC50 of Cd alone were 2 mg/L (95% CI: 0–4 mg/L) and 8 mg/L (95% CI: 2–17 mg/L), respectively. Cd alone significantly decreased the post-exposure predatory performance (PEPP) of M-est (≥6 mg/L) and L-est juveniles (≥3 mg/L), and acetylcholinesterase (AChE) activity of M-est juveniles (13 mg/L). MPs alone (0.14 mg/L) significantly reduced the PEPP and AChE activity of L-est juveniles but not of M-est juveniles. MPs-Cd mixtures (3–13 mg/L of Cd + 0.14 mg/L of MPs) significantly inhibited the PEPP of juveniles from both estuaries and AChE of L-est estuary juveniles but not of M-est juveniles. Evidences of toxicological interactions, namely antagonism, between MPs and Cd were found. Overall, the results indicate that MPs modulated the sub-lethal toxic effects of Cd in wild P. microps juveniles, especially neurotoxicity. Moreover, the environmental conditions of the natural habitats to which juveniles were exposed during pre-developmental phases influence the sub-lethal toxicity of Cd, MPs, and their mixtures. The implications to environmental and human risk assessment are discussed and further research is needed.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Neurotoxicity, Behavior, and Lethal Effects of Cadmium, Microplastics, and Their Mixtures on Pomatoschistus microps Juveniles from Two Wild Populations Exposed under Laboratory Conditions―Implications to Environmental and Human Risk Assessment

Miranda

Vieira

Guilhermino

2019

IJERPH

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“…Another major factor in the efficacy of CAQK-LIP-GFs/DTX@HP in treating SCI is the neuroprotection of GFs, including their local immune-modulatory action and effects in promoting neuronal plasticity 46 . It is widely acknowledged that a pronounced microglia/macrophage response is induced after SCI via the release of pro-inflammatory cytokines, nitric oxide (NO), and reactive oxygen species (ROS) by M1 macrophages 69 , 70 , which leads to ECM degradation, scar formation, neuron death and axon retraction 71 , 72 . Our data suggest that GFs likely promote tissue repair and ECM remodeling in part by inhibiting the spread of M1 macrophages and increasing the activation and/or proliferation of M2 macrophages during the early post-lesion phase.…”

Section: Discussionmentioning

confidence: 99%

Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

Wang

Zhang

et al. 2018

Theranostics

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Proper selection and effective delivery of combination drugs targeting multiple pathophysiological pathways key to spinal cord injury (SCI) hold promise to address the thus far scarce clinical therapeutics for improving recovery after SCI. In this study, we aim to develop a clinically feasible way for targeted delivery of multiple drugs with different physiochemical properties to the SCI site, detail the underlying mechanism of neural recovery, and detect any synergistic effect related to combination therapy.Methods: Liposomes (LIP) modified with a scar-targeted tetrapeptide (cysteine-alanine-glutamine-lysine, CAQK) were first constructed to simultaneously encapsulate docetaxel (DTX) and brain-derived neurotrophic factor (BDNF) and then were further added into a thermosensitive heparin-modified poloxamer hydrogel (HP) with affinity-bound acidic fibroblast growth factor (aFGF-HP) for local administration into the SCI site (CAQK-LIP-GFs/DTX@HP) in a rat model. In vivo fluorescence imaging was used to examine the specificity of CAQK-LIP-GFs/DTX binding to the injured site. Multiple comprehensive evaluations including biotin dextran amine anterograde tracing and magnetic resonance imaging were used to detect any synergistic effects and the underlying mechanisms of CAQK-LIP-GFs/DTX@HP both in vivo (rat SCI model) and in vitro (primary neuron).Results: The multiple drugs were effectively delivered to the injured site. The combined application of GFs and DTX supported neuro-regeneration by improving neuronal survival and plasticity, rendering a more permissive extracellular matrix environment with improved regeneration potential. In addition, our combination therapy promoted axonal regeneration via moderation of microtubule function and mitochondrial transport along the regenerating axon.Conclusion: This novel multifunctional therapeutic strategy with a scar-homing delivery system may offer promising translational prospects for the clinical treatment of SCI.

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“…This suggests the response to carbachol in myometrial arteries is less robust than that to bradykinin, which is consistent with our calcium signalling data. There is some evidence that oxidative stress, which is a feature of obesity, can cause a reduction in expression of M3 receptors . More specifically, Lin et al recently showed that a high fat diet led to decreased muscarinic M3 receptor expression in rat bladder.…”

Section: Resultsmentioning

confidence: 99%

Human myometrial artery function and endothelial cell calcium signalling are reduced by obesity: Can this contribute to poor labour outcomes?

Prendergast

Wray

2019

Acta Physiologica

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Aims:Determining how obesity affects function in human myometrial arteries, to help understand why childbirth has poor outcomes in obese women. Methods: Myometrial arteries were studied from 84 biopsies. Contraction (vasopressin and U-46619) and relaxation (carbachol, bradykinin, SNAP) was assessed using wire myography. eNOS activity was assessed using L-NAME. Cholesterol was reduced using methyl-β-cyclodextrin to determine whether it altered responses.Differences in endothelial cell intracellular Ca 2+ signalling were assessed using confocal microscopy. Results: The effects of BMI on relaxation were agonist specific and very marked; all vessels, irrespective of BMI, relaxed to bradykinin but 0% of vessels (0/13) from obese women relaxed to carbachol, compared to 59% (10/17) from normal weight women.Cholesterol-lowering drugs did not restore carbachol responses (n = 6). All vessels, irrespective of BMI, relaxed when NO was directly released by SNAP (n = 19).Inhibition of eNOS with L-NAME had a significant effect in normal but not overweight/obese vessels. Compared to bradykinin, a lower proportion of endothelial cells responded to carbachol and the amplitude of the calcium response was significantly less, in all vessels. Furthermore, a significantly lower proportion of endothelial cells responded to carbachol in the overweight/obese group compared to control. In contrast to relaxation, the effect of contractile agonists was unchanged with increasing BMI. Conclusions: The ability of human myometrial arteries to relax is significantly impaired with obesity, and our data suggest this is due to a deficit in endothelial calcium signalling. This inability to recover following compression during contractions, might contribute to poor labours in obese women. K E Y W O R D SBMI, Ca 2+ signalling, endothelium, myometrial arteries, obesity 2 of 15 |

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Cadmium induced ROS alters M1 and M3 receptors, leading to SN56 cholinergic neuronal loss, through AChE variants disruption

Cited by 37 publications

References 52 publications

Neurotoxicity, Behavior, and Lethal Effects of Cadmium, Microplastics, and Their Mixtures on Pomatoschistus microps Juveniles from Two Wild Populations Exposed under Laboratory Conditions―Implications to Environmental and Human Risk Assessment

Neurotoxicity, Behavior, and Lethal Effects of Cadmium, Microplastics, and Their Mixtures on Pomatoschistus microps Juveniles from Two Wild Populations Exposed under Laboratory Conditions―Implications to Environmental and Human Risk Assessment

Novel multi-drug delivery hydrogel using scar-homing liposomes improves spinal cord injury repair

Human myometrial artery function and endothelial cell calcium signalling are reduced by obesity: Can this contribute to poor labour outcomes?

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