Impairment in the mesohippocampal dopamine circuit following exposure to the brominated flame retardant, HBCDD

Pham-Lake, Camille; Aronoff, Elizabeth; Camp, Chad R.; Vester, Aimee; Peters, Sam J.; Caudle, W. Michael

doi:10.1016/j.etap.2017.02.003

Cited by 13 publications

(9 citation statements)

References 54 publications

(105 reference statements)

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“…Firstly, neurotransmission as an important mechanism how neuron conducts message and the impact on this can be known by measuring neurotransmitters as a biomarker (Boix et al 2010;Dingemans et al 2007;Gee et al 2011;Lei et al 2017;Moser et al 2015;Pham-Lake et al 2017;Wang et al 2015;Zhang et al 2018;Zhu et al 2018). Secondly, neurochannels balance ionic concentration inside and outside of the cell through voltage gated calcium channels and calcium could be a biomarker to study the ion channel mechanism (Mochida 2000;Dingemans et al 2007).…”

Section: Translational In Vivomentioning

confidence: 99%

An integrative translational framework for chemical induced neurotoxicity – a systematic review

Deepika

Sharma

Schuhmacher

et al. 2020

Critical Reviews in Toxicology

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Many chemicals in day-to-day and industrial usage have ability to cross the blood brain barrier and develop neurotoxicity in human beings. There are numerous in vitro, in vivo, epidemiological and in silico studies developed to test the neurotoxicity of such chemicals. This systematic review summarized the endpoints and biochemical markers generated from in vitro models, organism-based models, human studies and in silico tools and how they are being used to translate the data for risk assessment of neurotoxic chemicals. With the advancement in experimental studies such as high throughput screening (e.g. proteomics, genomics), there is a huge potential of data generation related to genes and proteins facilitating deep understanding of molecular mechanisms of neurotoxicity. However, this demand a translational platform that can integrate the biological data from different studies mechanistically and thereby translated across intra and interspecies for neurotoxicity assessment. Further, this review proposed an integrative translational framework to assess the chemicals for neurotoxicity.

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Section: Translational In Vivomentioning

confidence: 99%

An integrative translational framework for chemical induced neurotoxicity – a systematic review

Deepika

Sharma

Schuhmacher

et al. 2020

Critical Reviews in Toxicology

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“…GD0‐PND21 (Maurice et al., 2015), GD1‐PND0 (Miller‐Rhodes et al., 2014) and PND10‐PND70 (Zhang et al., 2017a), followed by behavioural analyses of the offspring at different ages. One study exposed adult animals for 6 weeks (Pham‐Lake et al., 2017) (see Table 10 ).…”

Section: Assessmentmentioning

confidence: 99%

“…Pham‐Lake et al. (2017) reported that 2‐month old male mice dosed with 25 mg/kg bw per day HBCDDs by gavage for 6 weeks, followed by a further 6 weeks without dosing, did not exhibit explicit behavioural abnormalities such as deficits in grooming, isolation, feeding or generalised movement. The absence of these effects does not necessarily contradict those observed by Eriksson et al.…”

Section: Assessmentmentioning

confidence: 99%

“…HBCDDs were found to inhibit dopamine uptake with a half maximal inhibitory concentration (IC50) of 4 μM (Mariussen and Fonnum, 2003). In the hippocampus, there was in addition reduced expression of proteins involved in synthesis (tyrosine hydroxylase) and degradation (catechol‐O‐methyltransferase and monoamine oxidase‐B) of dopamine (Pham‐Lake et al., 2017). These studies are supportive of effects of HBCDDs on presynaptic dopaminergic neurons.…”

Section: Assessmentmentioning

confidence: 99%

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Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food

Schrenk

Bignami

Bodin³

et al. 2021

EFS2

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The European Commission asked EFSA to update its 2011 risk assessment on hexabromocyclododecanes ( HBCDD s) in food. HBCDD s, predominantly mixtures of the stereoisomers α‐, β‐ and γ‐ HBCDD , were widely used additive flame retardants. Concern has been raised because of the occurrence of HBCDD s in the environment, food and in humans. Main targets for toxicity are neurodevelopment, the liver, thyroid hormone homeostasis and the reproductive and immune systems. The CONTAM Panel concluded that the neurodevelopmental effects on behaviour in mice can be considered the critical effects. Based on effects on spontaneous behaviour in mice, the Panel identified a lowest observed adverse effect level ( LOAEL ) of 0.9 mg/kg body weight (bw) as the Reference Point, corresponding to a body burden of 0.75 mg/kg bw. The chronic intake that would lead to the same body burden in humans was calculated to be 2.35 μg/kg bw per day. The derivation of a health‐based guidance value ( HBGV ) was not considered appropriate. Instead, the margin of exposure ( MOE ) approach was applied to assess possible health concerns. Over 6,000 analytical results for HBCDD s in food were used to estimate the exposure across dietary surveys and age groups of the European population. The most important contributors to the chronic dietary LB exposure to HBCDD s were fish meat, eggs, livestock meat and poultry. The CONTAM Panel concluded that the resulting MOE values support the conclusion that current dietary exposure to HBCDD s across European countries does not raise a health concern. An exception is breastfed infants with high milk consumption, for which the lowest MOE values may raise a health concern.

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“…Recent findings highlight VMAT2 as a vulnerable target to environmental toxicants (Caudle 2015;Caudle et al 2012). Animal studies suggest that a range of chemical exposures including pesticides, fungicides, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDE's), and perfluorinated compounds reduce the expression and function of VMAT2 and lead to symptoms closely resembling Parkinson's Disease (PD) (Bradner et al 2013;Caudle et al 2005;Choi et al 2015;Enayah et al 2018;Inamdar et al 2013;Miller et al 1999;Patel et al 2016;Pham-Lake et al 2017;Richardson et al 2006;Richardson et al 2008;Richardson and Miller 2004;Schuh et al 2009;Wilson et al 2014;Xiong et al 2016). Continued research into the effects of these chemicals on the function of amine transporters should improve our understanding of how they function to disrupt the vesicular integrity of the synaptic vesicle.…”

Section: Introductionmentioning

confidence: 99%

Genetic or toxicant induced disruption of vesicular monoamine storage and global metabolic profiling inCaenorhabditis elegans

Bradner

Kalia

Lau

et al. 2020

Preprint

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The proper storage and release of monoamines contributes to a wide range of neuronal activity. Here, we examine the effects of altered vesicular monoamine transport in the nematode C. elegans. The gene cat-1 is responsible for the encoding of the vesicular monoamine transporter (VMAT) in C. elegans and is analogous to the mammalian vesicular monoamine transporter 2 (VMAT2). Our laboratory has previously shown that reduced VMAT2 activity confers vulnerability on catecholamine neurons in mice. The purpose of this paper was to determine whether this function is conserved and to determine the impact of reduced VMAT activity in C. elegans. Here we show that deletion of cat-1/VMAT increases sensitivity to the neurotoxicant 1-methyl-4-phenylpyridinium (MPP+) as measured by enhanced degeneration of dopamine neurons. Reduced cat-1/VMAT also induces changes in dopamine-mediated behaviors. High-resolution mass spectrometry-based metabolomics in the whole organism reveals changes in amino acid metabolism, including tyrosine metabolism in the cat-1/VMAT mutants. Treatment with MPP+ disrupted tryptophan metabolism. Both conditions altered glycerophospholipid metabolism, suggesting a convergent pathway of neuronal dysfunction. Our results demonstrate the evolutionarily conserved nature of monoamine function in C. elegans and further suggest that HRMS-based metabolomics can be used in this model to study environmental and genetic contributors to complex human disease

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Impairment in the mesohippocampal dopamine circuit following exposure to the brominated flame retardant, HBCDD

Cited by 13 publications

References 54 publications

An integrative translational framework for chemical induced neurotoxicity – a systematic review

An integrative translational framework for chemical induced neurotoxicity – a systematic review

Update of the risk assessment of hexabromocyclododecanes (HBCDDs) in food

Genetic or toxicant induced disruption of vesicular monoamine storage and global metabolic profiling inCaenorhabditis elegans

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