7-Nitroindazole protects striatal neurons against MPP+ -induced degeneration.

Arcangelo Benigno, Giuseppe Crescimanno, Giuseppe Di Giovanni, Massimo Pierucci, Vincenzo Di Matteo, Ennio Esposito

Risultato della ricerca: Article

34 Citazioni (Scopus)

Abstract

The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP+) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP+-lesioned, and (c) 7-NI pretreated MPP+-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP+ was infused into the striatum for 10 min in the other two groups. The infusion of the MPP+ produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP+ was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP+ reperfusion in the MPP+-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP+-induced neurotoxicity. The similarity between the MPP+ model and PD suggests that NO may play a significant role in its etiology.
Lingua originaleEnglish
pagine (da-a)462-471
RivistaAnnals of the New York Academy of Sciences
Volume1089 (1)
Stato di pubblicazionePublished - 2006

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Corpus Striatum
Neurons
Rats
Parkinson Disease
Rat control
Nitric Oxide Synthase Type I
Macrophage Colony-Stimulating Factor
Iodides
Neuroprotective Agents
Dopaminergic Neurons
Microdialysis
Reperfusion
7-nitroindazole
Degeneration
Rat
Neuron
Experiments

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • History and Philosophy of Science
  • Biochemistry, Genetics and Molecular Biology(all)

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7-Nitroindazole protects striatal neurons against MPP+ -induced degeneration. / Benigno, Arcangelo; Crescimanno, Giuseppe; Di Giovanni, Giuseppe; Pierucci, Massimo; Di Matteo, Vincenzo; Esposito, Ennio.

In: Annals of the New York Academy of Sciences, Vol. 1089 (1), 2006, pag. 462-471.

Risultato della ricerca: Article

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abstract = "The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP+) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP+-lesioned, and (c) 7-NI pretreated MPP+-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP+ was infused into the striatum for 10 min in the other two groups. The infusion of the MPP+ produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP+ was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP+ reperfusion in the MPP+-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP+-induced neurotoxicity. The similarity between the MPP+ model and PD suggests that NO may play a significant role in its etiology.",
keywords = "NITRIC-OXIDE SYNTHASE; PARKINSONS-DISEASE; MPTP NEUROTOXICITY; RAT STRIATUM; NEURODEGENERATIVE DISEASES; TRANSPORTER ACTIVITY; LIPID-PEROXIDATION; MONOAMINE-OXIDASE; SODIUM-SALICYLATE; BRAIN",
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T1 - 7-Nitroindazole protects striatal neurons against MPP+ -induced degeneration.

AU - Benigno, Arcangelo

AU - Crescimanno, Giuseppe

AU - Di Giovanni, Giuseppe

AU - Pierucci, Massimo

AU - Di Matteo, Vincenzo

AU - Esposito, Ennio

PY - 2006

Y1 - 2006

N2 - The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP+) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP+-lesioned, and (c) 7-NI pretreated MPP+-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP+ was infused into the striatum for 10 min in the other two groups. The infusion of the MPP+ produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP+ was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP+ reperfusion in the MPP+-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP+-induced neurotoxicity. The similarity between the MPP+ model and PD suggests that NO may play a significant role in its etiology.

AB - The neuropathological hallmark of Parkinson's disease (PD) is the selective degeneration of dopaminergic (DAergic) neurons in the substantia nigra pars compacta (SNc). In this study, using a microdialysis technique, we investigated whether an inhibitor of neuronal nitric oxide synthase (nNOS), 7-nitrindazole (7-NI), could protect against DAergic neuronal damage induced by in vivo infusion of 1-methyl-4-phenylpiridinium iodide (MPP+) in freely moving rats. Experiments were performed over 2 days in three groups of rats: (a) nonlesioned, (b) MPP+-lesioned, and (c) 7-NI pretreated MPP+-lesioned rats. On day 1, control rats were perfused with an artificial CSF, while 1 mM MPP+ was infused into the striatum for 10 min in the other two groups. The infusion of the MPP+ produced a neurotoxic damage of the SNc DA neurons and increased striatal DA levels. On day 2, 1 mM MPP+ was reperfused for 10 min into the striata of each rat group and DA levels were measured as an index of neuronal cell integrity. The limited rise of DA following MPP+ reperfusion in the MPP+-lesioned rats was due to toxin-induced neuronal loss and was reversed by pretreatment with 7-NI (50 mg/kg, intraperitoneally) on day 1, indicating a neuroprotective effect by inhibiting NO formation. These results indicate that neuronally derived NO partially mediates MPP+-induced neurotoxicity. The similarity between the MPP+ model and PD suggests that NO may play a significant role in its etiology.

KW - NITRIC-OXIDE SYNTHASE; PARKINSONS-DISEASE; MPTP NEUROTOXICITY; RAT STRIATUM; NEURODEGENERATIVE DISEASES; TRANSPORTER ACTIVITY; LIPID-PEROXIDATION; MONOAMINE-OXIDASE; SODIUM-SALICYLATE; BRAIN

UR - http://hdl.handle.net/10447/15886

M3 - Article

VL - 1089 (1)

SP - 462

EP - 471

JO - Annals of the New York Academy of Sciences

JF - Annals of the New York Academy of Sciences

SN - 0077-8923

ER -