Intranigral Dopamine Toxicity and α-Synuclein Response in Rats

Gómez-Santos, Cristina; Giménez-Xavier, Pol; Ferrer, Isidre; Ambrosio, Santiago

doi:10.1007/s11064-006-9090-2

Cited by 6 publications

(3 citation statements)

References 43 publications

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“…It is well known that DA exerts its toxic effects in vitro , in primary cultures of dopaminergic, 31 cortical, 32 and striatal cells 33 and in vivo , by direct administration of DA in the rat brain, causing a consistent neuronal loss 34–36 . As previously mentioned, the mechanisms of DA‐induced toxicity are due to oxidative species.…”

Section: Dopamine‐induced Autophagymentioning

confidence: 97%

Role of Autophagy during Methamphetamine Neurotoxicity

Pasquali

Lazzeri

Isidoro³

et al. 2008

Annals of the New York Academy of Sciences

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Methamphetamine causes nigrostriatal denervation and striatal dopamine loss, while sparing nigral cell bodies. Nigral dopamine neurons feature autophagic vacuoles and cytoplasmic alpha-synuclein-, ubiquitin- and parkin-positive inclusion-like bodies. On that basis, autophagy was considered essential in methamphetamine-induced neurotoxicity, but its neurotoxic or protective role has never been addressed. Here we review the gap between the descriptive evidence on activation of autophagy and the lack of knowledge about its role during methamphetamine intoxication. Our preliminary findings rule out a detrimental role for autophagy; this represents the first step in understanding the consequence of activation of autophagy in methamphetamine toxicity.

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Section: Dopamine‐induced Autophagymentioning

confidence: 97%

Role of Autophagy during Methamphetamine Neurotoxicity

Pasquali

Lazzeri

Isidoro³

et al. 2008

Annals of the New York Academy of Sciences

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“…DA toxicity has been described in vivo and in vitro using stereotaxic administration [3,4] and several cell models [5][6][7] to determine the mechanisms that might underlie Parkinson's disease (PD). A disruption of DA regulation, linked to age or genetic predisposition, could lead to an imbalance between cytoplasmic and vesicular DA in the dopaminergic neuron, which might result in DA autoxidation, oxygen consumption, a hypoxia-like condition and, finally, cell death.…”

Section: Introductionmentioning

confidence: 99%

Dopamine induces TNFα and TNF-R1 expression in SH-SY5Y human neuroblastoma cells

Gómez-Santos

Francisco²,

Giménez-Xavier³

et al. 2007

NeuroReport

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Cytotoxic concentrations of dopamine (100-500 microM DA) induce expression of tumour necrosis factor receptor-1 (TNF-R1) and tumour necrosis factor-alpha (TNFalpha) in SH-SY5Y human neuroblastoma cells. TNFalpha expression is dose-dependent and can also be detected after 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium iodide (MPP) treatment. The expression of TNF-R1 is also dose-dependent, but was not observed in 6-OHDA or MPP-treatment. Cells not expressing TNF-R1 were insensitive to TNFalpha, whereas those treated with DA showed a further decrease in viability when subsequently treated with TNFalpha. Thus, DA treatment confers sensitivity to TNFalpha. The decrease of cell viability caused by DA was in part prevented by neutralizing TNFalpha with anti-TNFalpha. As TNF-R1 is increased in substantia nigra of Parkinsonian brains, we suggest that nonvesiculated DA might also play a role in inducing TNF-R1 expression and predispose the neuron to the action of cytokines released in a microglia-mediated inflammatory response.

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“…Moreover, elevated levels of DA or BH 4 , a cofactor required for DA synthesis, are neurotoxic in several model systems (Berman and Hastings 1999; Choi et al. 2003; Gomez‐Santos et al. 2006).…”

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confidence: 99%

Catecholamines up integrates dopamine synthesis and synaptic trafficking

Wang

Ferdousy

Lawal

et al. 2011

Journal of Neurochemistry

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The highly reactive nature of dopamine renders dopaminergic neurons vulnerable to oxidative damage. We recently demonstrated that loss-of-function mutations in the Drosophila gene Catecholamines up (Catsup) elevate dopamine pools but, paradoxically, also confer resistance to paraquat, an herbicide that induces oxidative stress-mediated toxicity in dopaminergic neurons. We now report a novel association of the membrane protein, Catsup, with GTP cyclohydrolase rate-limiting enzyme for tetrahydrobiopterin (BH4) biosynthesis and tyrosine hydroxylase, rate-limiting enzyme for dopamine biosynthesis, which requires BH4 as a cofactor. Loss-of-function Catsup mutations cause dominant hyperactivation of both enzymes. Elevated dopamine levels in Catsup mutants coincide with several distinct characteristics, including hypermobility, minimal basal levels of 3,4-Dihydroxy-Phenylacetic Acid, an oxidative metabolite of dopamine, and resistance to the Vesicular Monoamine Transporter inhibitor, reserpine, suggesting that excess dopamine is synaptically active and that Catsup functions in the regulation of synaptic vesicle loading and release of dopamine. We conclude that Catsup regulates and links the dopamine synthesis and transport networks.

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Intranigral Dopamine Toxicity and α-Synuclein Response in Rats

Cited by 6 publications

References 43 publications

Role of Autophagy during Methamphetamine Neurotoxicity

Role of Autophagy during Methamphetamine Neurotoxicity

Dopamine induces TNFα and TNF-R1 expression in SH-SY5Y human neuroblastoma cells

Catecholamines up integrates dopamine synthesis and synaptic trafficking

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