Inflammatory priming of the substantia nigra influences the impact of later paraquat exposure: Neuroimmune sensitization of neurodegeneration

Mangano, Emily; Hayley, Shawn

doi:10.1016/j.neurobiolaging.2007.11.020

Cited by 88 publications

(147 citation statements)

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“…Since inflammation also plays a role in PQ toxicity (Mangano and Hayley, 2009), we measured the transcript levels of Il6 and Tnfa, cytokines of the early response to PQ, and found no differential expression by genotype or chronic PQ treatment in the SN (not shown). Recently, we have found that acute high doses of PQ induce ApoD-dependent oligodendrocyte gene expression responses in the cerebellum (Bajo-Grañeras et al, 2011).…”

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confidence: 94%

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

Bajo‐Grañeras¹,

Ganfornina²,

Martín-Tejedor³

et al. 2011

Glia

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The study of glial derived factors induced by injury and degeneration is important to understand the nervous system response to deteriorating conditions. We focus on Apolipoprotein D (ApoD), a Lipocalin expressed by glia and strongly induced upon aging, injury or neurodegeneration.Here we study ApoD function in the brain of wild type and ApoD-KO mice by combining in vivo experiments with astrocyte cultures. Locomotor performance, dopamine concentration, and gene expression levels in the substantia nigra were assayed in mice treated with paraquat (PQ). The regulation of ApoD transcription, a molecular screening of oxidative stress (OS)-related genes, cell viability and oxidation status, and the effects of adding human ApoD were tested in astrocyte cultures. We demonstrate that (1) ApoD is required for an adequate locomotor performance, modifies the gene expression profile of PQ-challenged nigrostriatal system, and contributes to its functional maintenance; (2) ApoD expression in astrocytes is controlled by the OSresponsive JNK pathway; (3) ApoD contributes to an autocrine protecting mechanism in astrocytes, avoiding peroxidated lipids accumulation and altering the PQ transcriptional response of genes involved in ROS managing and the inflammatory response to OS; (4) Addition of human ApoD to ApoD-KO astrocytes promotes survival through a mechanism accompanied by protein internalization and modulation of astroglial reactivity. Our data support that ApoD contributes to the endurance of astrocytes and decreases their reactivity level in vitro and in vivo. ApoD function as a maintenance factor for astrocytes would suffice to explain the observed protection by ApoD of OS-vulnerable dopaminergic circuits in vivo. V

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confidence: 94%

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

Bajo‐Grañeras¹,

Ganfornina²,

Martín-Tejedor³

et al. 2011

Glia

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“…dose, timing of treatment, species or strain, age of animal, iron accumulation, strain specific gene ontology) can explain contradictory effects observed following treatment with the chemical stressor paraquat in mice. Fei et al, 2008;Cristovao et al, 2009;Fernagut et al, 2009;Mangano et al, 2009Mangano et al, , 2011Watson, 2013;. In order to integrate data on paraquat toxicity from widely different experimental models, ranging from cell cultures to repeat dose animal studies, the concentrations close to the target site were compared by classical approaches of in vitro in vivo extrapolation (IVIVE) based on the available publications.…”

Section: Weight Of Evidence For the Ker Biological Plausibilitymentioning

confidence: 99%

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Ockleford¹,

Adriaanse²,

Berny³

et al. 2017

EFS2

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In 2013, EFSA published a literature review on epidemiological studies linking exposure to pesticides and human health outcome. As a follow up, the EFSA Panel on Plant Protection Products and their residues (PPR Panel) was requested to investigate the plausible involvement of pesticide exposure as a risk factor for Parkinson's disease (PD) and childhood leukaemia (CHL). A systematic literature review on PD and CHL and mode of actions for pesticides was published by EFSA in 2016 and used as background documentation. The Panel used the Adverse Outcome Pathway (AOP) conceptual framework to define the biological plausibility in relation to epidemiological studies by means of identification of specific symptoms of the diseases as AO. The AOP combines multiple information and provides knowledge of biological pathways, highlights species differences and similarities, identifies research needs and supports regulatory decisions. In this context, the AOP approach could help in organising the available experimental knowledge to assess biological plausibility by describing the link between a molecular initiating event (MIE) and the AO through a series of biologically plausible and essential key events (KEs). As the AOP is chemically agnostic, tool chemical compounds were selected to empirically support the response and temporal concordance of the key event relationships (KERs). Three qualitative and one putative AOP were developed by the Panel using the results obtained. The Panel supports the use of the AOP framework to scientifically and transparently explore the biological plausibility of the association between pesticide exposure and human health outcomes, identify data gaps, define a tailored testing strategy and suggests an AOP's informed Integrated Approach for Testing and Assessment (IATA).

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“…Within microglia PQ increases NADPH oxidase expression possibly due to the ROS produced by the PQ redox cycle, mitochondria or after activation of NF-κB [36,37]. Activated microglia releases inflammatory cytokines and O 2 − radicals, which damage the adjacent neurons.…”

Section: Oxidative Stressmentioning

confidence: 99%

Paraquat: Molecular Mechanisms of Neurotoxicity and its Relation with Autophagy

Baltazar

Dinis-Oliveira

Bastos

et al. 2015

Current Topics in Neurotoxicity

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Paraquat (1,1´-dimethyl-4,4´-bipyridilium dichloride; PQ) is an effective and widely used herbicide in Asiatic and American countries with a claimed safety record when appropriately applied to eliminate weeds. However, over the last decades a growing body of epidemiologic evidence has been linking longterm/low-dose PQ exposure to the development of Parkinson's disease (PD). PQ is well known for its ability to induce oxidative stress, mitochondrial dysfunction, α-synuclein fibrillation and neuronal cell loss. More recently, more attention has been given to the role of autophagy in several major neurodegenerative diseases and the influence of environmental toxins in this pathway. This chapter provides an overview of the main mechanisms of neurotoxicity of PQ with an emphasis in the autophagic process and its possible relationship to PD.Keywords Paraquat · Oxidative stress · Autophagy · Neurotoxicity · Neurodegenerative diseases 160 M. T. Baltazar et al.

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Inflammatory priming of the substantia nigra influences the impact of later paraquat exposure: Neuroimmune sensitization of neurodegeneration

Cited by 88 publications

References 100 publications

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

Apolipoprotein D mediates autocrine protection of astrocytes and controls their reactivity level, contributing to the functional maintenance of paraquat-challenged dopaminergic systems

Investigation into experimental toxicological properties of plant protection products having a potential link to Parkinson's disease and childhood leukaemia†

Paraquat: Molecular Mechanisms of Neurotoxicity and its Relation with Autophagy

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