Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally

Ling, Zaodung; Chang, Qing; Tong, Chong Wai; Leurgans, Susan E.; Lipton, Jack W.; Carvey, Paul M.

doi:10.1016/j.expneurol.2004.08.006

Cited by 119 publications

(105 citation statements)

References 57 publications

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“…There is strong evidence to support the notion that disturbances in neural developmental processes in utero caused by prenatal exposure to immunogens are a risk factor for the development of various psychopathologies such as schizophrenia (Brown et al, 2004;Mednick et al, 1988;O'Callaghan et al, 1994), attention deficit/hyperactivity disorder (Vuillermot et al, 2012), depression (Ling et al, 2004;Winter et al, 2009) and autism (Miller et al, 2005;Rodier and Hyman, 1998). In fact, both human and animal studies of prenatal immune activation have revealed abnormalities in adult brain cytoarchitecture, such as reduced dendritic arborization and abnormal neuronal migration (Deutsch et al, 2010;Fatemi and Folsom, 2009), suggesting a neurodevelopmental origin for some psychiatric illnesses that takes place prior to the onset of symptoms.…”

Section: Introductionmentioning

confidence: 99%

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Rana

Aavani

Pittman

2012

Hormones and Behavior

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Humans are exposed to potentially harmful agents (bacteria, viruses, toxins) throughout our lifespan; the consequences of such exposure can alter central nervous system development. Exposure to immunogens during pregnancy increases the risk of developing neurological disorders such as schizophrenia and autism. Further, sex hormones, such as estrogen, have strong modulatory effects on immune function and have also been implicated in the development of neuropathologies (e.g., schizophrenia and depression). Similarly, animal studies have demonstrated that immunogen exposure in utero or during the neonatal period, at a time when the brain is undergoing maturation, can induce changes in learning and memory, as well as dopaminemediated behaviors in a sex-specific manner. Literature that covers the effects of immunogens on innate immune activation and ultimately the development of the adult brain and behavior is riddled with contradictory findings, and the addition of sex as a factor only adds to the complexity. This review provides evidence that innate immune activation during critical periods of development may have effects on the adult brain in a sex-specific manner. Issues regarding sex bias in research as well as variability in animal models of immune function are discussed.

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Section: Introductionmentioning

confidence: 99%

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Rana

Aavani

Pittman

2012

Hormones and Behavior

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“…The brains were removed and immediately placed in cold 2-methylbutane, and then stored at −80°C. The TNF-α and IL-1β levels were determined for both studies as previously described (Ling et al, 2004). Briefly, brains were slightly thawed, the SNs and striata dissected out, then submerged in ice-cold 150μl homogenate buffer (Trizma/HCl pH 7.2, 0.1 M, sodium chloride 0.9%, protease inhibitor cocktail 1%), and sonicated.…”

Section: Elisa For Determination Of Tnf-α and Il-1β Concentration In mentioning

confidence: 99%

“…Briefly, a 10X objective lens was used to define the contour around the entire SN (Ling et al, 2004) and a 100X lens was used for the tyrosine hydroxylase immunoreactive cells (THir cells) and activated microglia assessments. One series of sections from each animal was analyzed for THir and a second series for CD 11b staining.…”

Section: Stereological Assessment Of Thir Cell and Activated Microglimentioning

confidence: 99%

TNF-α knockout and minocycline treatment attenuates blood–brain barrier leakage in MPTP-treated mice

Zhao

Ling

Newman

et al. 2007

Neurobiology of Disease

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119

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Following intraparenchymal injection of the dopamine (DA) neurotoxin 6-hydroxydopamine, we previously demonstrated passage of fluoresceinisothiocyanate labeled albumin (FITC-LA) from blood into the substantia nigra (SN) and striatum suggesting damage to the blood-brain barrier (BBB). The factors contributing to the BBB leakage could have included neuroinflammation, loss of DA neuron control of barrier function, or a combination of both. In order to determine which factor(s) was responsible, we assessed BBB integrity using the FITC-LA technique in wild-type (WT), tumor necrosis factor alpha (TNF-α) knockout (KO), and minocycline (an inhibitor of microglia activation) treated mice 72 hrs following treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Compared with WT mice, TNF-α KO mice treated with MPTP, showed reduced FITC-LA leakage, decreased numbers of activated microglia, and reduced pro-inflammatory cytokines (TNF-α and interleukin 1β) associated with significant MPTP-induced DA neuron loss. In contrast, minocycline treated animals did not exhibit significant MPTP-induced DA neuron loss although their FITC-LA leakage, numbers of activated microglia, and MPTP-induced cytokines were markedly attenuated. Since both TNF-α KO and minocycline treatment attenuated MPTP-induced BBB dysfunction, microglial activation, and cytokine increases, but had differential effects on DA neuron loss, it appears that neuroinflammation and not DA neuron loss was responsible for disrupting the bloodbrain barrier integrity.

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“…This finding was suggested to reflect an ongoing neurodegenerative process that persisted years after the initial toxic injury and could have been perpetuated, at least in part, by chronic neuroinflammation (Langston et al, 1999). Microglia have also been implicated in the production of reactive oxygen species (ROS) and the selective degeneration of nigrostriatal dopaminergic neurons caused by MPTP and other neurotoxicants in animal models and in vitro experimental paradigms (Gao et al, 2003a and b;Sherer et al, 2003;Wu et al, 2003;Ling et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration

Purisai

McCormack

Cumine

et al. 2007

Neurobiology of Disease

231

215

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Dopaminergic cells in the substantia nigra are highly vulnerable to the neurodegenerative process of Parkinson's disease. Therefore, mechanisms that enhance their susceptibility to injury bear important implications for disease pathogenesis. Repeated injections with the herbicide paraquat cause oxidative stress and a selective loss of dopaminergic neurons in mice. In this model, the first paraquat exposure, though not sufficient to induce any neurodegeneration, predisposes neurons to damage by subsequent insults. The purpose of this study was to elucidate the mechanisms underlying this "priming" event. We found that a single paraquat exposure was followed by an increase in the number of cells with immunohistochemical, morphological and biochemical characteristics of activated microglia, including induction of NADPH-oxidase. If this microglial response was inhibited by the anti-inflammatory drug minocycline, subsequent exposures to the herbicide failed to cause oxidative stress and neurodegeneration. On the other hand, if microglial activation was induced by pretreatment with lipopolysaccharide, a single paraquat exposure became capable of triggering a loss of dopaminergic neurons. Finally, mutant mice lacking functional NADPH-oxidase were spared from neurodegeneration caused by repeated paraquat exposures. Data indicate that microglial activation and consequent induction of NADPH-oxidase may act as risk factors for Parkinson's disease by increasing the vulnerability of dopaminergic cells to toxic injury.

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Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally

Cited by 119 publications

References 57 publications

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

Sex effects on neurodevelopmental outcomes of innate immune activation during prenatal and neonatal life

TNF-α knockout and minocycline treatment attenuates blood–brain barrier leakage in MPTP-treated mice

Microglial activation as a priming event leading to paraquat-induced dopaminergic cell degeneration

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