Neurotoxicity of pesticides

Richardson, Jason R.; Fitsanakis, Vanessa A.; Westerink, Remco H.S.; Kanthasamy, Anumantha G.

doi:10.1007/s00401-019-02033-9

Cited by 363 publications

(188 citation statements)

References 202 publications

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“…4-hydroxy-2-nonenal) and higher concentration of α-syn [4,154]. Pesticides and heavy metal exposure has been linked to development of PD [126] and their addition in vitro has also been shown to accelerate oligomerization and aggregation of α-syn [154]. In fact, fractioning fibrilized α-syn by sonication into smaller fragments and injecting that material into the brains of rodents causes human like PD pathology [1].…”

Section: Protein Aggregationmentioning

confidence: 99%

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Biological links between traumatic brain injury and Parkinson’s disease

Delic

Beck

Pang

et al. 2020

acta neuropathol commun

111

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Parkinson's Disease (PD) is a progressive neurodegenerative disorder with no cure. Clinical presentation is characterized by postural instability, resting tremors, and gait problems that result from progressive loss of A9 dopaminergic neurons in the substantia nigra pars compacta. Traumatic brain injury (TBI) has been implicated as a risk factor for several neurodegenerative diseases, but the strongest evidence is linked to development of PD. Mild TBI (mTBI), is the most common and is defined by minimal, if any, loss of consciousness and the absence of significant observable damage to the brain tissue. mTBI is responsible for a 56% higher risk of developing PD in U.S. Veterans and the risk increases with severity of injury. While the mounting evidence from human studies suggests a link between TBI and PD, fundamental questions as to whether TBI nucleates PD pathology or accelerates PD pathology in vulnerable populations remains unanswered. Several promising lines of research point to inflammation, metabolic dysregulation, and protein accumulation as potential mechanisms through which TBI can initiate or accelerate PD. Amyloid precursor protein (APP), alpha synuclein (α-syn), hyper-phosphorylated Tau, and TAR DNA-binding protein 43 (TDP-43), are some of the most frequently reported proteins upregulated following a TBI and are also closely linked to PD. Recently, upregulation of Leucine Rich Repeat Kinase 2 (LRRK2), has been found in the brain of mice following a TBI. Subset of Rab proteins were identified as biological substrates of LRRK2, a protein also extensively linked to late onset PD. Inhibition of LRRK2 was found to be neuroprotective in PD and TBI models. The goal of this review is to survey current literature concerning the mechanistic overlap between TBI and PD with a particular focus on inflammation, metabolic dysregulation, and aforementioned proteins. This review will also cover the application of rodent TBI models to further our understanding of the relationship between TBI and PD.

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Section: Protein Aggregationmentioning

confidence: 99%

“…Exposure to neurotoxins has been shown to cause PD later in life [126]. Exposure to neurotoxins may increase susceptibility to subsequent injuries like TBI that bring about clinical presentation of PD.…”

Section: Controlled Cortical Impact (Cci) Tbimentioning

confidence: 99%

Biological links between traumatic brain injury and Parkinson’s disease

Delic

Beck

Pang

et al. 2020

acta neuropathol commun

111

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“…Individual compounds belonging to POPs are well‐known neurotoxins. For example, they have been reported to induce cognitive, motor, and behavioral deficits in animal models through multiple mechanisms, such as changes in neurotransmitter systems, altered intracellular signaling processes, and thyroid hormone imbalance . Furthermore, a wide range of inorganic and organic environmental chemicals, including heavy metals and contemporary pesticides, are also suspected neurotoxins .…”

Section: New Hypothesismentioning

confidence: 99%

“…For example, they have been reported to induce cognitive, motor, and behavioral deficits in animal models through multiple mechanisms, such as changes in neurotransmitter systems, altered intracellular signaling processes, and thyroid hormone imbalance. [18][19][20][21] Furthermore, a wide range of inorganic and organic environmental chemicals, including heavy metals and contemporary pesticides, are also suspected neurotoxins. 22 Nevertheless, it is difficult to uncover solid evidence in humans linking low-dose chronic exposure to specific compounds to dementia, as people are simultaneously exposed to many environmental chemicals.…”

Section: Lipophilic Chemical Mixtures As Neurotoxinsmentioning

confidence: 99%

Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study

Lee

Park

Lee

2020

Alzheimer's & Dementia

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Objective The aim of this paper is to propose a new hypothesis for the role of lipophilic chemical mixtures stored in adipose tissue in the development of dementia. Specifically, we present how the dynamics of these chemicals can explain the unexpected findings from the Action for Health in Diabetes (Look AHEAD) study, which failed to show long‐term benefits of intentional weight loss on cognition, despite substantial improvements in many known risk factors for dementia. Moreover, we discuss how the role of obesity in the risk of dementia can change depending on the dynamics of these chemicals in adipose tissue. New hypothesis Human adipose tissue is widely contaminated with various neurotoxic chemicals. Typical examples are persistent organic pollutants (POPs), strong lipophilic chemicals with long half‐lives. Both unintentional and intentional weight loss increases the release of POPs from adipocytes into the circulation. As POPs in the blood can easily reach the brain, the intentional weight‐loss group of the Look AHEAD study may have experienced an unappreciated and long‐term disadvantage on their cognition. Additionally, POPs may be involved in the link between obesity and dementia, as dysfunctional hypertrophic adipocytes enhance the release of POPs from adipocytes to the circulation through uncontrolled lipolysis. In contrast, metabolically healthy obese people may have a low risk of dementia because the safe storage of POPs in adipose tissue would decrease the amount of POPs reaching the brain. Major challenges for the hypothesis In human studies, there are practical difficulties involved with measuring POPs in the blood, including high costs and complex assays. As the serum concentrations of POPs are continuously affected by weight loss and gain, prospective studies may require serial measurements of POPs. In in‐vitro and in‐vivo experimental studies, how to simulate the exposure dose, duration, and mixture patterns in humans would be critical. Linkage to other major theories Even though POPs are direct neurotoxins at a high dosage, low‐dose POPs are mitochondrial toxins. Therefore, chronic exposure to low‐dose POPs is linked to known key interrelated mechanisms in the pathogenesis of dementia, such as mitochondrial dysfunction and neuroinflammation.

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“…As for AD, the exact underlying causes for the development of neurodegenerative diseases remain unknown in the majority of cases (for review see [7]). However, growing bodies of evidence suggest that chronic exposure to certain chemical compounds, notably pesticides and some metals, can be neurotoxic and favor the development of neurodegenerative disorders (see [8][9][10] and references therein). Taking into account that humans are susceptible to be exposed, even at low doses, to plant Int.…”

Section: Introductionmentioning

confidence: 99%

Long-Term Fipronil Treatment Induces Hyperactivity in Female Mice

Koslowski

Latapy

Auvray

et al. 2020

IJERPH

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Fipronil is an insecticide widely used for veterinary and agricultural purposes. While its insecticidal properties mostly rely on its high affinity antagonistic activity on insect γ aminobutyric acid (GABA) receptors, fipronil and its main metabolite fipronil sulfone nevertheless display non-negligible affinity for mammalian GABA A receptor. As several environmental toxicants have been shown to raise the risk of developing various neurodegenerative disorders, the aim of this study was to evaluate whether long-term low dose administration of fipronil could lead to cognitive deficiencies. Our results indicate that long-term fipronil treatment leads to behavioral perturbations in mice, indicating an accumulative effect of sustained exposure to low dose of fipronil. Although no memory impairment was observed during the course of our study, we noticed a significant hyperlocomotion behavior after 43 weeks of weekly fipronil administration, which is consistent with its direct effect on the GABAergic system.

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Neurotoxicity of pesticides

Cited by 363 publications

References 202 publications

Biological links between traumatic brain injury and Parkinson’s disease

Biological links between traumatic brain injury and Parkinson’s disease

Intensive weight loss and cognition: The dynamics of persistent organic pollutants in adipose tissue can explain the unexpected results from the Action for Health in Diabetes (Look AHEAD) study

Long-Term Fipronil Treatment Induces Hyperactivity in Female Mice

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