Neonatal rotenone lesions cause onset of hyperactivity during juvenile and adulthood in the rat

Ishido, Masami; Suzuki, Junko; Masuo, Yoshinori

doi:10.1016/j.toxlet.2016.12.008

Cited by 10 publications

(7 citation statements)

References 27 publications

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“…As mentioned above, rotenone has been shown to be a dopaminergic toxin, developing Parkinson's disease with adult rats (Betarbet et al, 2000;Ishido and Shimaya, 2016) and we demonstrated that exposure of rat pups to rotenone causes hyperactivity during juvenile and adulthood due to dopaminergic lesions by rotenone (Ishido et al, 2017).…”

Section: Rotenone and Behavioral Phenotypessupporting

confidence: 61%

“…Thus, spontaneous motor activity of these two kinds of animal models could be quantitative index. We employed Supermex® system to measure spontaneous motor activity, as described previously ( Masuo et al ., 1997( Masuo et al ., , 2007Masuo and Ishido, 2011 ;Ishido et al ., , 2004cIshido et al ., , 2004dIshido et al ., , 2005Ishido et al ., , 2017Ishido and Shimaya, 2016 ). A Supermex® sensor head comprising paired infrared pyroelectric detectors was used to measure the radiated body heat of each animal.…”

Section: Measurements Of Spontaneous Motor Activity For Behavioral Phmentioning

confidence: 99%

“…Gene expression levels were calculated as the ratio of expression level in the exposed rat brain to that in the control rat brain. Table 1 lists the typical changes of levels in gene expression of molecules in the midbrain at 11 weeks of age (Ishido et al, 2017). It is noteworthy that relatively many genes related to apoptosis/cell cycle were altered in their expres-sion; Baz1b, Prkcd, Dhrs7, Rnf138, Anapc1, Ssn, Ste, and Igfbp5.…”

Section: The Gene Expression Profiles Of Rat Behavioral Phenotypesmentioning

confidence: 99%

“…To compare the transcriptome of rat hyperactivity dis- Adapted from ref. Shimaya, 2016 andIshido et al, 2017. Table 1.…”

Section: The Gene Expression Profiles Of Rat Behavioral Phenotypesmentioning

confidence: 99%

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The temporal turning window for rat behavioral phenotypes by rotenone

Ishido

2018

Fundam. Toxicol. Sci.

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Availability of animal models of human neuronal disease has been contributing to reveal their etiology. Particularly, dopaminergic neurodegeneration has been shown by exposure of rats to chemicals, such as rotenone, corresponding to the rat models of attention deficit hyperactivity disorder (ADHD) and Parkinson's disease. A single chemical of rotenone causes two behavioral phenotypes, both of which are completely opposite; hyperactivity or hypoactivity. They were created by different timing of chemical exposure, neonatal periods or adulthood, suggesting that there would be a temporal turning point of two behavioral phenotypes. Therefore, we examine a turning point of these behavioral phenotypes by measuring the spontaneous motor activity of rotenone models. We estimate the turning window of both behavioral phenotypes would be around between three weeks and four weeks of age in the rat dopaminergic neurodegeneration. Gene set enrichment analysis extracts a cytokine network in both rat models.

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Section: Rotenone and Behavioral Phenotypessupporting

confidence: 61%

Section: Measurements Of Spontaneous Motor Activity For Behavioral Phmentioning

confidence: 99%

Section: The Gene Expression Profiles Of Rat Behavioral Phenotypesmentioning

confidence: 99%

“…To compare the transcriptome of rat hyperactivity dis- Adapted from ref. Shimaya, 2016 andIshido et al, 2017. Table 1.…”

Section: The Gene Expression Profiles Of Rat Behavioral Phenotypesmentioning

confidence: 99%

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The temporal turning window for rat behavioral phenotypes by rotenone

Ishido

2018

Fundam. Toxicol. Sci.

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“…For example, D. rerio embryos exposed to rotenone showed embryotoxic effects, showing cardiac edema; tail deformities; loss of equilibrium; and a general delay characterized by lack of tail detachment, delayed somite formation, yolk sac absorption, and lack of pigmentation (Melo et al, 2015). In addition, Neonatal rotenone lesions derived into hyperactivity during juvenile stage in rats (Ishido et al, 2017). To try to identify developmental pathways modified metabolomics and transcriptomics was performed.…”

Section: Discussionmentioning

confidence: 99%

Rotenone exerts developmental neurotoxicity in a human brain spheroid model

Pamies

Block

Lau

et al. 2018

Toxicology and Applied Pharmacology

120

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Growing concern suggests that some chemicals exert (developmental) neurotoxicity (DNT and NT) and are linked to the increase in incidence of autism, attention deficit and hyperactivity disorders. The high cost of routine tests for DNT and NT assessment make it difficult to test the high numbers of existing chemicals. Thus, more cost effective neurodevelopmental models are needed. The use of induced pluripotent stem cells (iPSC) in combination with the emerging human 3D tissue culture platforms, present a novel tool to predict and study human toxicity. By combining these technologies, we generated multicellular brain spheroids (BrainSpheres) from human iPSC. The model has previously shown to be reproducible and recapitulates several neurodevelopmental features. Our results indicate, rotenone’s toxic potency varies depending on the differentiation status of the cells, showing higher reactive oxygen species (ROS) and higher mitochondrial dysfunction during early than later differentiation stages. Immunofluorescence morphology analysis after rotenone exposure indicated dopaminergic-neuron selective toxicity at non-cytotoxic concentrations (1 μM), while astrocytes and other neuronal cell types were affected at (general) cytotoxic concentrations (25 μM). Omics analysis showed changes in key pathways necessary for brain development, indicating rotenone as a developmental neurotoxicant and show a possible link between previously shown effects on neurite outgrowth and presently observed effects on Ca2+ reabsorption, synaptogenesis and PPAR pathway disruption. In conclusion, our BrainSpheres model has shown to be a reproducible and novel tool to study neurotoxicity and developmental neurotoxicity. Results presented here support the idea that rotenone can potentially be a developmental neurotoxicant.

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Integration of Health Risk Assessment for Various Chemicals: Common Biomarkers in Different Exposure Routes

Ishido

2023

Health Risk Assessment of Environmental Chemicals

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Neonatal rotenone lesions cause onset of hyperactivity during juvenile and adulthood in the rat

Cited by 10 publications

References 27 publications

The temporal turning window for rat behavioral phenotypes by rotenone

The temporal turning window for rat behavioral phenotypes by rotenone

Rotenone exerts developmental neurotoxicity in a human brain spheroid model

Integration of Health Risk Assessment for Various Chemicals: Common Biomarkers in Different Exposure Routes

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