Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice

Keane, P.C.; Hanson, Peter S.; Patterson, Lina; Blain, Peter G.; Hepplewhite, Philippa D.; Khundakar, Ahmad; Judge, Sarah J.; Kahle, Philipp J.; LeBeau, Fiona E. N.; Morris, Christopher M.

doi:10.1016/j.neulet.2019.134437

Cited by 21 publications

(19 citation statements)

References 33 publications

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“…Increasing the dilution results in reduction of the intensity both the specific and background staining; nevertheless, the specific immunoreaction was still visible at a dilution of 1:1,000,000. These data are contradictory to those obtained by several laboratories using this antiserum at 1:2000 dilutions (one even at 1:00 dilution 14 ) with the exception of Henderson et al 15,16 who used these antibodies at a higher 1:20,000 dilutions. Unfortunately, none of the large A-C), 1:1,000,000 (D-F), and 1:4,000,000 (G-I).…”

Section: Immunohistochemistrycontrasting

confidence: 61%

A Forgotten Principle in Immunocytochemistry: Optimal Dilution

Dudás

Lane

Mupparaju

et al. 2022

J Histochem Cytochem.

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Immunocytochemical (ICC) techniques are frequently used in basic and clinical research. Here, we focus on the importance of using antisera/antibodies at optimal dilutions to achieve specificity and reduce costs. Unfortunately, the basic principle, the necessity to test method specificity of the staining by a series of increasing dilutions of primary antiserum/antibodies, is only occasionally seen in papers using ICC. Many researchers rely on the company’s information or others’ published data. In this study, we show examples with monoclonal antibodies used in the peroxidase-based ICC technique in mouse and guinea pig brain sections. We show images of ICC staining of phospho-S129 alpha-synuclein in A53T mice and NeuN in guinea pig brains and demonstrate that optimal staining with them can be achieved at least at two to three orders of magnitude higher dilutions than generally used in the literature. We strongly recommend that when antisera/antibodies are used for the first time in any laboratory, independent of what the manufacturer or vendor recommends or are found in the literature, a dilution curve should be set up to identify the optimal dilution. This practice provides not only the highest specificity but is also an economic approach.

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Section: Immunohistochemistrycontrasting

confidence: 61%

A Forgotten Principle in Immunocytochemistry: Optimal Dilution

Dudás

Lane

Mupparaju

et al. 2022

J Histochem Cytochem.

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“…The different results can be due to high inter‐individual differences in α‐syn pathology in A30P‐tg mice (Fagerqvist et al., 2013), or limitations in the study design, including the low sample size and the quantification method used. Previous studies examining the TH immunoreactivity in A30P‐tg mice have recorded subtle signs of disturbed homeostasis in the dopaminergic neurons (Ekmark‐Lewén et al., 2018; Fauser et al., 2021; Keane et al., 2019; Neuner et al., 2014; Rathke‐Hartlieb et al., 2001), yet yielded differential results with respect to α‐syn pathology depending on the methods used and are not in complete consensus.…”

Section: Discussionmentioning

confidence: 99%

Visualization of early oligomeric α‐synuclein pathology and its impact on the dopaminergic system in the (Thy‐1)‐h[A30P]α‐syn transgenic mouse model

Behere

Thörnqvist

Winberg

et al. 2021

J of Neuroscience Research

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The histopathological hallmark of the Parkinson's disease (PD) brain is the presence of Lewy bodies (LBs) and Lewy neurites (LNs), intraneuronal lipid-and protein-rich complexes mainly consisting of fibrillar alpha-synuclein (α-syn) (Spillantini et al., 1997). Misfolding of native α-syn causes dynamic changes in its conformation, leading to formation of oligomers followed by protofibrillar species and finally

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“…70 , 71 Similarly, animal models exposed to TCE have shown nigrostriatal degeneration, which led to the mitochondrial dysfunction and the development of parkinsonian features. 64 , 72 …”

Section: Mitochondrial Toxicants and Neurodegenerationmentioning

confidence: 99%

Mitochondrial Toxicant-Induced Neuronal Apoptosis in Parkinson’s Disease: What We Know so Far

Sivagurunathan¹,

Gnanasekaran²,

Latchoumycandane³

2023

DNND

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Parkinson’s disease (PD) is one of the most common progressive neurodegenerative diseases caused by the loss of dopamine-producing neuronal cells in the region of substantia nigra pars compacta of the brain. During biological aging, neuronal cells slowly undergo degeneration, but the rate of cell death increases tremendously under some pathological conditions, leading to irreversible neurodegenerative diseases. By the time symptoms of PD usually appear, more than 50 to 60% of neuronal cells have already been destroyed. PD symptoms often start with tremors, followed by slow movement, stiffness, and postural imbalance. The etiology of PD is still unknown; however, besides genetics, several factors contribute to neurodegenerative disease, including exposure to pesticides, environmental chemicals, solvents, and heavy metals. Postmortem brain tissues of patients with PD show mitochondrial abnormalities, including dysfunction of the electron transport chain. Most chemicals present in our environment have been shown to target the mitochondria; remarkably, patients with PD show a mild deficiency in NADH dehydrogenase activity, signifying a possible link between PD and mitochondrial dysfunction. Inhibition of electron transport complexes generates free radicals that further attack the macromolecules leading to neuropathological conditions. Apart from that, oxidative stress also causes neuroinflammation-mediated neurodegeneration due to the activation of microglial cells. However, the mechanism that causes mitochondrial dysfunction, especially the electron transport chain, in the pathogenesis of PD remains unclear. This review discusses the recent updates and explains the possible mechanisms of mitochondrial toxicant-induced neuroinflammation and neurodegeneration in PD.

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Trichloroethylene and its metabolite TaClo lead to degeneration of substantia nigra dopaminergic neurones: Effects in wild type and human A30P mutant α-synuclein mice

Cited by 21 publications

References 33 publications

A Forgotten Principle in Immunocytochemistry: Optimal Dilution

A Forgotten Principle in Immunocytochemistry: Optimal Dilution

Visualization of early oligomeric α‐synuclein pathology and its impact on the dopaminergic system in the (Thy‐1)‐h[A30P]α‐syn transgenic mouse model

Mitochondrial Toxicant-Induced Neuronal Apoptosis in Parkinson’s Disease: What We Know so Far

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