Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone

Fleming, Sheila M.; Zhu, Chunni; Fernagut, Pierre‐Olivier; Mehta, Arpesh; DiCarlo, Cheryl Dawn; Seaman, Ronald L.; Chesselet, Marie‐Françoise

doi:10.1016/j.expneurol.2004.01.023

Cited by 202 publications

(156 citation statements)

References 55 publications

Supporting

Mentioning

143

Contrasting

Unclassified

Order By: Relevance

“…1 After systemic administration of 2 to 3 mg/kg per day, the concentration of free rotenone in the brain is approximately 20 to 30 nmol/L. 4,5 In addition, Talpade et al 4 suggested that 1 to 30 nmol/L of rotenone may be a reasonable concentration in the living rat brain under rotenone-triggered pathological conditions. Based on these reports, we used 1 to 30 nmol/L of rotenone in our present study.…”

Section: Discussionmentioning

confidence: 99%

“…3 It is a highly lipophilic pesticide that readily crosses the bloodbrain barrier and accumulates throughout the brain. 4,5 Rotenone exposure has disrupted cell membranes and caused damage to proteins, lipids, and DNA, ultimately leading to neuronal cell death. Indeed, there is increasing evidence that long-term exposure to rotenone causes significant degenerative diseases.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Rotenone exposure has emerged as an environmental risk factor for inflammation-associated neurodegenerative diseases. However, the underlying mechanisms responsible for the harmful effects of rotenone in the brain remain poorly understood. Herein, we report that myeloperoxidase (MPO) may have a potential regulatory role in rotenone-exposed brain-resident immune cells. We show that microglia, unlike neurons, do not undergo death; instead, they exhibit distinctive activated properties under rotenone-exposed conditions. Once activated by rotenone, microglia show increased production of reactive oxygen species, particularly HOCl. Notably, MPO, an HOClproducing enzyme that is undetectable under normal conditions, is significantly increased after exposure to rotenone. MPO-exposed glial cells also display characteristics of activated cells, producing proinflammatory cytokines and increasing their phagocytic activity. Interestingly, our studies with MPO inhibitors and MPO-knockout mice reveal that MPO deficiency potentiates, rather than inhibits, the rotenone-induced activated state of glia and promotes glial cell death. Furthermore, rotenone-triggered neuronal injury was more apparent in co-cultures with glial cells from Mpo ؊/؊ mice than in those from wildtype mice. Collectively, our data provide evidence that MPO has dual functionality under rotenone-exposed conditions, playing a critical regulatory role in modulating pathological and protective events in the brain.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Chang

Song

Jeon

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Chronic exposure of Drosophila melanogaster to rotenone also models sporadic Parkinson's disease (Coulom and Birman, 2004). However, other studies have questioned whether rotenone-induced motor abnormalities result from a loss of dopaminergic neurons (Perier et al, 2003;Fleming et al, 2004;Lapointe et al, 2004) and challenged the idea that rotenone induces selective loss of dopaminergic neurons (Hoglinger et al, 2003). In this study, we showed that, at low concentrations of rotenone (1-5 nM), dopaminergic neurons were much more sensitive to rotenone-induced cell loss than the general cellular population in E14 mesencephalic primary neuron cultures.…”

Section: Discussionmentioning

confidence: 99%

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

Hsuan¹,

Klintworth²,

Xia³

2006

J. Neurosci.

View full text Add to dashboard Cite

Administration of rotenone to rats reproduces many features of Parkinson's disease, including dopaminergic neuron degeneration, and provides a useful model to study the pathogenesis of Parkinson's disease. However, the cell death mechanisms induced by rotenone and potential neuroprotective mechanisms against rotenone are not well defined. Here we report that rotenone-induced apoptosis in human dopaminergic SH-SY5Y cells is attenuated by pretreatment with several growth factors, most notably basic fibroblast growth factor (bFGF). bFGF activated both extracellular signal-regulated kinase 1/2 (ERK1/2) and phosphatidylinositol-3 kinase (PI3-kinase) pathways in SH-SY5Y cells. Ectopic activation of ERK1/2 or PI3-kinase protected against rotenone, whereas inhibition of either pathway attenuated bFGF protection. Reducing the expression of the proapoptotic protein Bcl-2-associated death protein (BAD) by small interfering RNA rendered SH-SY5Y cells resistant to rotenone, implicating BAD in rotenone-induced cell death. Interestingly, bFGF induced a long-lasting phosphorylation of BAD at serine 112, suggesting BAD inactivation through the ERK1/2 signaling pathway. Moreover, primary cultured dopaminergic neurons from mesencephalon were more sensitive to rotenone-induced cell death than nondopaminergic neurons in the same culture. The loss of dopaminergic neurons was blocked by bFGF, an inhibition dependent on ERK1/2 and PI3-kinase signaling. These data suggest that rotenone-induced dopaminergic cell death requires BAD and identify bFGF and its activation of ERK1/2 and PI3-kinase signaling pathways as novel intervention strategies to block cell death in the rotenone model of Parkinson's disease.

show abstract

“…The primary concern is related to the high variability in animal sensitivity and the inability of other investigators to consistently reproduce the parkinsonian neuropathology and phenotype of this model (Hoglinger et al 2003;Fleming et al 2004b;Lapointe et al 2004;Zhu et al 2004). To address these concerns, a revised rotenone model has been developed ).…”

Section: Rotenonementioning

confidence: 99%

A Guide to Neurotoxic Animal Models of Parkinson's Disease

Tieu¹

2011

Cold Spring Harbor Perspectives in Medicine

410

299

View full text Add to dashboard Cite

Parkinson's disease (PD) is a neurological movement disorder primarily resulting from damage to the nigrostriatal dopaminergic pathway. To elucidate the pathogenesis, mechanisms of cell death, and to evaluate therapeutic strategies for PD, numerous animal models have been developed. Understanding the strengths and limitations of these models can significantly impact the choice of model, experimental design, and data interpretation. The primary objectives of this article are twofold: First, to assist new investigators who are contemplating embarking on PD research to navigate through the available animal models. Emphasis will be placed on common neurotoxic murine models in which toxic molecules are used to lesion the nigrostriatal dopaminergic system. And second, to provide an overview of basic technical requirements for assessing the pathology, structure, and function of the nigrostriatal pathway.

show abstract

Behavioral and immunohistochemical effects of chronic intravenous and subcutaneous infusions of varying doses of rotenone

Cited by 202 publications

References 55 publications

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Dual Functionality of Myeloperoxidase in Rotenone-Exposed Brain-Resident Immune Cells

Basic Fibroblast Growth Factor Protects against Rotenone-Induced Dopaminergic Cell Death through Activation of Extracellular Signal-Regulated Kinases 1/2 and Phosphatidylinositol-3 Kinase Pathways

A Guide to Neurotoxic Animal Models of Parkinson's Disease

Contact Info

Product

Resources

About